Implementation of a scalable, web-based, automated clinical decision support risk-prediction tool for chronic kidney disease using C-CDA and application programming interfaces.

PubMed

Samal, Lipika; D'Amore, John D; Bates, David W; Wright, Adam

2017-11-01

Clinical decision support tools for risk prediction are readily available, but typically require workflow interruptions and manual data entry so are rarely used. Due to new data interoperability standards for electronic health records (EHRs), other options are available. As a clinical case study, we sought to build a scalable, web-based system that would automate calculation of kidney failure risk and display clinical decision support to users in primary care practices. We developed a single-page application, web server, database, and application programming interface to calculate and display kidney failure risk. Data were extracted from the EHR using the Consolidated Clinical Document Architecture interoperability standard for Continuity of Care Documents (CCDs). EHR users were presented with a noninterruptive alert on the patient's summary screen and a hyperlink to details and recommendations provided through a web application. Clinic schedules and CCDs were retrieved using existing application programming interfaces to the EHR, and we provided a clinical decision support hyperlink to the EHR as a service. We debugged a series of terminology and technical issues. The application was validated with data from 255 patients and subsequently deployed to 10 primary care clinics where, over the course of 1 year, 569 533 CCD documents were processed. We validated the use of interoperable documents and open-source components to develop a low-cost tool for automated clinical decision support. Since Consolidated Clinical Document Architecture-based data extraction extends to any certified EHR, this demonstrates a successful modular approach to clinical decision support. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Laparoscopic sterilization with the spring clip: instrumentation development and current clinical experience.

PubMed

Hulka, J F; Omran, K; Lieberman, B A; Gordon, A G

1979-12-15

Since the original spring clip sterilization studies were reported, a number of clinically important modifications to the spring clip and applicator have been developed. The spring-loaded clip, manufactured by Richard Wolf Medical Instruments Corporation of Chicago, Illinois, and Rocket of London, Inc., London, England, and New York, New York can be applied with either a one- or two-incision applicator and the clips and applicators currently available incorporate improvements to the original prototypes in design, manufacture, and quality control. The two-incision applicator is associated with significantly fewer misapplications and the high pregnancy rates reported with the original clip and applicator have not occurred with the current designs. Comparative studies between the clip and band have revealed less operative bleeding and pain associated with the clip. The method is appropriate to all women requesting sterilization but especially to those in the younger age group who may subsequently request reversal because of divorce and remarriage.

Clinical application of neurotrophic factors: the potential for primary auditory neuron protection

PubMed Central

Gillespie, Lisa N.; Shepherd, Robert K.

2007-01-01

Sensorineural hearing loss, as a result of damage to or destruction of the sensory epithelia within the cochlea, is a common cause of deafness. The subsequent degeneration of the neural elements within the inner ear may impinge upon the efficacy of the cochlear implant. Experimental studies have demonstrated that neurotrophic factors can prevent this degeneration in animal models of deafness, and can even provide functional benefits. Neurotrophic factor therapy may, therefore, provide similar protective effects in humans, resulting in improved speech perception outcomes among cochlear implant patients. There are, however, numerous issues pertaining to delivery techniques and treatment regimes which need to be addressed prior to any clinical application. This review considers these issues in view of the potential therapeutic application of neurotrophic factors within the auditory system. PMID:16262651

Breast Reference Set Application: Chris Li-FHCRC (2015) — EDRN Public Portal

Cancer.gov

We propose to evaluate nine candidate biomarkers for ER+ breast cancer in samples from the EDRN Breast Cancer Reference Set. These biomarkers have been preliminarily validated in preclinical samples. The intended clinical applications of these markers are to: 1. Inform timing of a subsequent mammogram in women with a negative screening mammogram; 2. Inform continuation of mammographic screening among women 75-79 years; 3. Prioritize women who should be screened with mammography in areas with limited resources. Testing the reference samples would further expedite addressing these intended clinical applications by providing further validation data to support requests for samples from other sources for further Phase 3 evaluation (e.g., WHI, PLCO, and samples collected at the time of mammographic screening from the University of Toronto and UCSF).

Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

NASA Astrophysics Data System (ADS)

Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

2015-12-01

The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera.

PubMed

Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

2015-01-01

The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

Ten years since the discovery of iPS cells: The current state of their clinical application.

PubMed

Aznar, J; Tudela, J

On the 10-year anniversary of the discovery of induced pluripotent stem cells, we review the main results from their various fields of application, the obstacles encountered during experimentation and the potential applications in clinical practice. The efficacy of induced pluripotent cells in clinical experimentation can be equated to that of human embryonic stem cells; however, unlike stem cells, induced pluripotent cells do not involve the severe ethical difficulties entailed by the need to destroy human embryos to obtain them. The finding of these cells, which was in its day a true scientific milestone worthy of a Nobel Prize in Medicine, is currently enveloped by light and shadow: high hopes for regenerative medicine versus the, as of yet, poorly controlled risks of unpredictable reactions, both in the processes of dedifferentiation and subsequent differentiation to the cell strains employed for therapeutic or experimentation goals. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens

PubMed Central

Loudig, Olivier; Wang, Tao; Ye, Kenny; Lin, Juan; Wang, Yihong; Ramnauth, Andrew; Liu, Christina; Stark, Azadeh; Chitale, Dhananjay; Greenlee, Robert; Multerer, Deborah; Honda, Stacey; Daida, Yihe; Spencer Feigelson, Heather; Glass, Andrew; Couch, Fergus J.; Rohan, Thomas; Ben-Dov, Iddo Z.

2017-01-01

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens. PMID:28335433

Medical student appraisal: applications for bedside patient education.

PubMed

Markman, T M; Sampognaro, P J; Mitchell, S L; Weeks, S R; Khalifian, S; Dattilo, J R

2013-01-01

Medical students are often afforded the privilege of counselling patients. In the past resources were limited to pen and paper or anatomic models. The evolution of mobile applications allows for limitless access to resources that facilitate bedside patient education. To evaluate the utility of six applications in patient education and promote awareness of implementing mobile resources in clinical care. Six medical students rotating on various clerkships evaluated a total of six mobile applications. Strengths, limitations, and suggested uses in clinical care were identified. Applications included Meditoons™, VisiblePatient™, DrawMD™, CardioTeach™, Visual Anatomy™, and 360° Patient Education Suite™. Data was generated from narrative responses supplied by each student during their evaluation period. Bedside teaching was enhanced by professional illustrations and animations depicting anatomy and pathophysiology. Impromptu teaching was facilitated, as resources were conveniently available on a student's smartphone or tablet. The ability to annotate and modify images and subsequently email to patients was an extraordinary improvement in provider-patient communication. Universal limitations included small smartphone screens and the novelty of new technology. Mobile applications have the potential to greatly enhance patient education and simultaneously build rapport. Endless opportunities exist for their integration in clinical practice, particularly for new diagnoses, consent for procedures, and at time of discharge. Providers should be encouraged to try new applications and utilize them with patients.

Universal suprapubic approach for complete mesocolic excision and central vascular ligation using the da Vinci Xi® system: from cadaveric models to clinical cases.

PubMed

Yeo, Shen Ann; Noh, Gyoung Tae; Han, Jeong Hee; Cheong, Chinock; Stein, Hubert; Kerdok, Amy; Min, Byung Soh

2017-12-01

There has been little enthusiasm for performing robotic colectomy for colon cancer in recent years due to multiple factors, one being that the previous robotic systems such as the da Vinci Si ® (dVSi) were poorly designed for multi-quadrant surgery. The new da Vinci Xi ® (dVXi) system enables colectomy with central mesocolic excision to be performed easily in a single docking procedure. We developed a universal port placement strategy to allow right and left hemicolectomies to be performed via a suprapubic approach and a Pfannensteil extraction site. This proof of concept paper describes the development and subsequent clinical application of this setup. After extensive training on the dVXi system concepts in collaboration with clinical development engineers, we developed a port placement strategy which was tested and adapted after performing experimental surgery in three cadaveric models. Subsequently our port placement was used for two clinical cases of suprapubic right and left hemicolectomy. With some modifications of port placements after the initial cadaveric colectomies, we have developed a potentially universal suprapubic port placement strategy for robotic colectomy with complete mesocolic excision and central vascular ligation using the dVXi robotic system. This port placement strategy was applied successfully in our first two clinical cases. Based on our cadaveric laboratory as well as our initial clinical application, the suprapubic port placement strategy for the dVXi system with its improved features over the dVSi can feasibly perform right and left hemicolectomy with complete mesocolic excision and central vascular ligation. Further studies will be required to establish efficacy as well as safety profile of these procedures.

[Severe complications after non-intended usage of octenidine dihydrochloride. A case series with four dogs].

PubMed

Kaiser, S; Kramer, M; Thiel, C

2015-01-01

Case series of four dogs in which extensive bite wounds had been treated using octenidine dihydrochloride (Octenivet® or Octenisept®) flushing. The dogs subsequently developed severe local complications. Retrospective evaluation of clinical symptoms, diagnostics, therapy and course of the disease. In four dogs, severe necrosis and persistent edematous changes of the treated area developed after the application of octenidine dihydrochloride. The clinical course was comparable to complications described previously in human medicine. Therapy was protracted and complicated by secondary wound infection. Irrigation of deep wounds, particularly bite wounds, using octenidine dihydrochloride without drainage may lead to persistent edematous changes, inflammatory reactions and necrosis. The inappropriate application of octenidine dihydrochloride for wound irrigation should be avoided in veterinary medicine.

Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in Cancer Therapy.

PubMed

Bishnoi, Suman; Tiwari, Ritudhwaj; Gupta, Sharad; Byrareddy, Siddappa N; Nayak, Debasis

2018-02-23

Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor cells. Although a number of apoptosis-induction approaches are available, site-specific delivery of therapeutic agents still remain the biggest hurdle in achieving the desired cancer treatment benefit. Additionally, systemic treatment-induced toxicity remains a major limiting factor in chemotherapy. To specifically address drug-accessibility and chemotherapy side effects, oncolytic virotherapy (OV) has emerged as a novel cancer treatment alternative. In OV, recombinant viruses with higher replication capacity and stronger lytic properties are being considered for tumor cell-targeting and subsequent cell lysing. Successful application of OVs lies in achieving strict tumor-specific tropism called oncotropism, which is contingent upon the biophysical interactions of tumor cell surface receptors with viral receptors and subsequent replication of oncolytic viruses in cancer cells. In this direction, few viral vector platforms have been developed and some of these have entered pre-clinical/clinical trials. Among these, the Vesicular stomatitis virus (VSV)-based platform shows high promise, as it is not pathogenic to humans. Further, modern molecular biology techniques such as reverse genetics tools have favorably advanced this field by creating efficient recombinant VSVs for OV; some have entered into clinical trials. In this review, we discuss the current status of VSV based oncotherapy, challenges, and future perspectives regarding its therapeutic applications in the cancer treatment.

Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in Cancer Therapy

PubMed Central

Bishnoi, Suman; Tiwari, Ritudhwaj; Gupta, Sharad; Byrareddy, Siddappa N.; Nayak, Debasis

2018-01-01

Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor cells. Although a number of apoptosis-induction approaches are available, site-specific delivery of therapeutic agents still remain the biggest hurdle in achieving the desired cancer treatment benefit. Additionally, systemic treatment-induced toxicity remains a major limiting factor in chemotherapy. To specifically address drug-accessibility and chemotherapy side effects, oncolytic virotherapy (OV) has emerged as a novel cancer treatment alternative. In OV, recombinant viruses with higher replication capacity and stronger lytic properties are being considered for tumor cell-targeting and subsequent cell lysing. Successful application of OVs lies in achieving strict tumor-specific tropism called oncotropism, which is contingent upon the biophysical interactions of tumor cell surface receptors with viral receptors and subsequent replication of oncolytic viruses in cancer cells. In this direction, few viral vector platforms have been developed and some of these have entered pre-clinical/clinical trials. Among these, the Vesicular stomatitis virus (VSV)-based platform shows high promise, as it is not pathogenic to humans. Further, modern molecular biology techniques such as reverse genetics tools have favorably advanced this field by creating efficient recombinant VSVs for OV; some have entered into clinical trials. In this review, we discuss the current status of VSV based oncotherapy, challenges, and future perspectives regarding its therapeutic applications in the cancer treatment. PMID:29473868

[Robotics].

PubMed

Bier, J

2000-05-01

Content of this paper is the current state of the art of robots in surgery and the ongoing work on the field of surgical robotics at the Clinic for Maxillofacial Surgery at the Charité. Robots in surgery allows the surgeon to transform the accuracy of the imaging systems directly during the intervention and to plan an intervention beforehand. In this paper firstly the state of the art is described. Subsequently the scientific work at the clinic is described in detail. The paper closes with a outlook for future applications of robotics systems in maxillofacial surgery.

Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application.

PubMed

Hajishengallis, George; Hajishengallis, Evlambia; Kajikawa, Tetsuhiro; Wang, Baomei; Yancopoulou, Despina; Ricklin, Daniel; Lambris, John D

2016-06-01

Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complement activity. Consistently, subsequent genetic and pharmacological studies in rodents have implicated the central complement component C3 and downstream signaling pathways in periodontal host-microbe interactions that promote dysbiosis and inflammatory bone loss. This review discusses these mechanistic advances and moreover focuses on the compstatin family of C3 inhibitors as a novel approach to treat periodontitis. In this regard, local application of the current lead analog Cp40 was recently shown to block both inducible and naturally occurring periodontitis in non-human primates. These promising results from non-human primate studies and the parallel development of Cp40 for clinical use highlight the feasibility for developing an adjunctive, C3-targeted therapy for human periodontitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Salvage microbiology: opportunities and challenges in the detection of bacterial pathogens following initiation of antimicrobial treatment

PubMed Central

Farrell, John J.; Hujer, Andrea M.; Sampath, Rangarajan; Bonomo, Robert A.

2015-01-01

Broad-range 16S ribosomal RNA gene PCR coupled with Sanger sequencing was originally employed by soil scientists and was subsequently adapted for clinical applications. PCR coupled with electrospray ionization mass spectrometry has also progressed from initial applications in the detection of organisms from environmental samples into the clinical realm and has demonstrated promise in detection of pathogens in clinical specimens obtained from patients with suspected infection but negative cultures. We review studies of multiplex PCR, 16S ribosomal RNA gene PCR and sequencing and PCR coupled with electrospray ionization mass spectrometry for detection of bacteria in specimens that were obtained from patients during or after administration of antibiotic treatment, and examine the role of each for assisting in antimicrobial treatment and stewardship efforts. Following an exploration of the available data in this field we discuss the opportunities that the preliminary investigations reveal, as well as the challenges faced with implementation of these strategies in clinical practice. PMID:25523281

Access control based on attribute certificates for medical intranet applications.

PubMed

Mavridis, I; Georgiadis, C; Pangalos, G; Khair, M

2001-01-01

Clinical information systems frequently use intranet and Internet technologies. However these technologies have emphasized sharing and not security, despite the sensitive and private nature of much health information. Digital certificates (electronic documents which recognize an entity or its attributes) can be used to control access in clinical intranet applications. To outline the need for access control in distributed clinical database systems, to describe the use of digital certificates and security policies, and to propose the architecture for a system using digital certificates, cryptography and security policy to control access to clinical intranet applications. We have previously developed a security policy, DIMEDAC (Distributed Medical Database Access Control), which is compatible with emerging public key and privilege management infrastructure. In our implementation approach we propose the use of digital certificates, to be used in conjunction with DIMEDAC. Our proposed access control system consists of two phases: the ways users gain their security credentials; and how these credentials are used to access medical data. Three types of digital certificates are used: identity certificates for authentication; attribute certificates for authorization; and access-rule certificates for propagation of access control policy. Once a user is identified and authenticated, subsequent access decisions are based on a combination of identity and attribute certificates, with access-rule certificates providing the policy framework. Access control in clinical intranet applications can be successfully and securely managed through the use of digital certificates and the DIMEDAC security policy.

A Versatile Microarray Platform for Capturing Rare Cells

NASA Astrophysics Data System (ADS)

Brinkmann, Falko; Hirtz, Michael; Haller, Anna; Gorges, Tobias M.; Vellekoop, Michael J.; Riethdorf, Sabine; Müller, Volkmar; Pantel, Klaus; Fuchs, Harald

2015-10-01

Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or incubation protocol, allows virtual arbitrary targeting of capture species and therefore wide spread applications in biomedical sciences.

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2014-01-01

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

Development of a smartphone application for eating disorder self-monitoring.

PubMed

Tregarthen, Jenna P; Lock, James; Darcy, Alison M

2015-11-01

This case report aims to (1) describe the development and refinement of a smartphone application for eating disorder self-monitoring; (2) characterize its users in terms of demographic and clinical characteristics; and (3) explore its feasibility and utilization as a self-monitoring tool. We developed a mobile phone application through which people with eating disorders can self-monitor meals, emotions, behaviors, and thoughts. The application also included positive reinforcement, coping skill suggestions, social support, and feedback components. The app was made available on two Internet app stores. Data include number of downloads and subsequent usage statistics, consumer ratings on app-stores are used as indicators of satisfaction, anonymous aggregate demographic data and Eating Disorder Examination Questionnaire scores from 57,940 individuals collected over a two-year period. The app demonstrated population-level utilization with over 100,000 users over a two-year period. Almost 50% percent of users stated that they are not currently receiving clinical treatment and 33% reported they had not told anyone about their eating disorder. A surprising number of people with severe problems are using the app. Smartphone apps have the capacity to reach and engage traditionally underserved individuals with eating disorders at a large scale. Additional work is indicated for the evaluation of the clinical effectiveness of applications for specific user groups and in clinical treatment contexts. © 2015 Wiley Periodicals, Inc.

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Frontiers of monoclonal antibodies: Applications in medical practices.

PubMed

Ghagane, Shridhar C; Puranik, Sridevi I; Gan, Siew Hua; Hiremath, Murigendra B; Nerli, R B; Ravishankar, M V

2017-01-01

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.

Decreased clinical pregnancy and live birth rates after short interval from delivery to subsequent assisted reproductive treatment cycle.

PubMed

Quinn, Molly M; Rosen, Mitchell P; Allen, Isabel Elaine; Huddleston, Heather G; Cedars, Marcelle I; Fujimoto, Victor Y

2018-06-15

Does the interval from delivery to initiation of a subsequent ART treatment cycle impact clinical pregnancy or live birth rates? An interval from delivery to treatment start of <6 months or ≥24 months is associated with decreased likelihood of clinical pregnancy and live birth. Short interpregnancy intervals are associated with poor obstetric outcomes in the naturally conceiving population prompting birth spacing recommendations of 18-24 months from international organizations. Deferring a subsequent pregnancy attempt means a woman will age in the interval with an attendant decline in her fertility. Retrospective analysis of the Society for Assisted Reproductive Technology Clinical Outcome Reporting System (SARTCORS) cohort containing 61 686 ART cycles from 2004 to 2013. The delivery-to-cycle interval (DCI) was calculated for patients from SARTCORS with a history of live birth from ART who returned to the same clinic for a first subsequent treatment cycle. Generalized linear models were fit to determine the risk of clinical pregnancy and live birth by DCI with subsequent adjustment for factors associated with outcomes of interest. Predicted probabilities of clinical pregnancy and live birth were generated from each model. A DCI of <6 months was associated with a 5.6% reduction in probability of clinical pregnancy (40.1 ± 1.9 versus 45.7 ± 0.6%, P = 0.009) and 6.8% reduction in live birth (31.6 ± 1.7 versus 38.4 ± 0.6%, P = 0.001) per cycle start compared to a DCI of 12 to <18 months. A DCI of ≥24 months was associated with a 5.1% reduction in probability of clinical pregnancy (40.6 ± 0.5 versus 45.7 ± 0.6%, P < 0.001) and 5.7% reduction in live birth (32.7 ± 0.5 versus 38.4 ± 0.6%, P < 0.001) compared to 12 to <18 months. The SART database is reliant upon self-report of many variables of interest including live birth. It remains unclear whether poorer outcomes are a result of residual confounding from factors inherent to the population with a very short or long DCI or the interval itself. Birth spacing recommendations for naturally conceiving populations may not be generally applicable to patients with a history of infertility. Patients planning ART treatment should wait a minimum of 6 months, but not more than 24 months, from a live birth for optimization of clinical pregnancy and live birth rates. National Center for Advancing Translational Sciences, National Institutes of Health, UCSF-CTSI Grant number UL1TR001872. The authors have no competing interests.

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

PubMed

Kardos, Nelson; Demain, Arnold L

2011-11-01

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today. These same technologies became the model for the development and production of new types of bioproducts (i.e., anticancer agents, monoclonal antibodies, and industrial enzymes). The clinical impact of penicillin was large and immediate. By ushering in the widespread clinical use of antibiotics, penicillin was responsible for enabling the control of many infectious diseases that had previously burdened mankind, with subsequent impact on global population demographics. Moreover, the large cumulative public effect of the many new antibiotics and new bioproducts that were developed and commercialized on the basis of the science and technology after penicillin demonstrates that penicillin had the greatest therapeutic impact event of all times. © Springer-Verlag 2011

A novel cardiac extracorporeal shock wave for enhancing the efficacy of cell therapy

NASA Astrophysics Data System (ADS)

Khaled, Walaa; Assmus, Birgit; Lutz, Andreas; Walter, Dirk; Leistner, David; Dimmeler, Stefanie; Zeiher, Andreas

2012-11-01

Targeted therapy can maximize therapeutic efficiency and minimize the side effects of drug treatments, especially for cancer and cardiovascular disease. In previous in-vitro experiments, it was shown that shock wave (SW) application can change the permeability of cell membranes for tumor therapy. Similarly, in animal studies, extracorporeal SWs were proven to increase expression of growth and homing factors like SDF-1 and vascular endothelial growth factor (VEGF) within a targeted ischemic tissue. This pretreatment increased the homing and neovascularization following application of bone marrow-derived mononuclear cells (BMC). In a randomized, double blinded, placebo-controlled clinical trial, 103 patients were recruited with stable chronic post-infarction heart failure (CHF). The goal of this work was to demonstrate improved recovery of left ventricular contractile function (LVEF) by combining targeted SW application with subsequent BMC administration. Results showed that the shock wavefacilitated intracoronary BMC administration in patients with chronic post-infarction heart failure is associated with significant persistent improvements in LVEF contractile function, NYHA class, and reduction of major adverse clinical events during extended clinical follow-up. (clinicaltrials.gov: NCT00326989).

Applications of Chondrocyte-Based Cartilage Engineering: An Overview

PubMed Central

Eo, Seong-Hui; Abbas, Qamar; Ahmed, Madiha

2016-01-01

Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes. PMID:27631002

Personalized skincare: from molecular basis to clinical and commercial applications.

PubMed

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare.

Personalized skincare: from molecular basis to clinical and commercial applications

PubMed Central

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare. PMID:29692619

Silk Fibroin Biomaterial Shows Safe and Effective Wound Healing in Animal Models and a Randomized Controlled Clinical Trial.

PubMed

Zhang, Wei; Chen, Longkun; Chen, Jialin; Wang, Lingshuang; Gui, Xuexian; Ran, Jisheng; Xu, Guowei; Zhao, Hongshi; Zeng, Mengfeng; Ji, Junfeng; Qian, Li; Zhou, Jianda; Ouyang, Hongwei; Zou, Xiaohui

2017-05-01

Due to its excellent biological and mechanical properties, silk fibroin has been intensively explored for tissue engineering and regenerative medicine applications. However, lack of translational evidence has hampered its clinical application for tissue repair. Here a silk fibroin film is developed and its translational potential is investigated for skin repair by performing comprehensive preclinical and clinical studies to fully evaluate its safety and effectiveness. The silk fibroin film fabricated using all green chemistry approaches demonstrates remarkable characteristics, including transmittance, fluid handling capacity, moisture vapor permeability, waterproofness, bacterial barrier properties, and biocompatibility. In vivo rabbit full-thickness skin defect study shows that the silk fibroin film effectively reduces the average wound healing time with better skin regeneration compared with the commercial wound dressings. Subsequent assessment in porcine model confirms its long-term safety and effectiveness for full-thickness skin defects. Finally, a randomized single-blind parallel controlled clinical trial with 71 patients shows that the silk fibroin film significantly reduces the time to wound healing and incidence of adverse events compared to commercial dressing. Therefore, the study provides systematic preclinical and clinical evidence that the silk fibroin film promotes wound healing thereby establishing a foundation towards its application for skin repair and regeneration in the clinic. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shrinkage Stresses Generated during Resin-Composite Applications: A Review

PubMed Central

Schneider, Luis Felipe J.; Cavalcante, Larissa Maria; Silikas, Nick

2010-01-01

Many developments have been made in the field of resin composites for dental applications. However, the manifestation of shrinkage due to the polymerization process continues to be a major problem. The material's shrinkage, associated with dynamic development of elastic modulus, creates stresses within the material and its interface with the tooth structure. As a consequence, marginal failure and subsequent secondary caries, marginal staining, restoration displacement, tooth fracture, and/or post-operative sensitivity are clinical drawbacks of resin-composite applications. The aim of the current paper is to present an overview about the shrinkage stresses created during resin-composite applications, consequences, and advances. The paper is based on results of many researches that are available in the literature. PMID:20948573

PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

Cancer.gov

We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

The Search for Perpetual Motion: Fatigue, Friction, and Drag in Quality Improvement.

PubMed

Cumbler, Ethan; Pierce, Read

Most people who have worked on continuous quality improvement (QI) with teams in the clinical microsystem have experienced "change fatigue." Application of the "Limit-to-Growth" system archetype to QI teams within health care can be used to understand negative feedback loops generated by successful QI that can limit future progress. Awareness of these factors can result in actions designed to reduce drag on forward momentum. Leaders in health care QI can anticipate and minimize negative feedback loops that accumulate to slow subsequent progress of highly functioning improvement teams within clinical microsystems.

Access Control based on Attribute Certificates for Medical Intranet Applications

PubMed Central

Georgiadis, Christos; Pangalos, George; Khair, Marie

2001-01-01

Background Clinical information systems frequently use intranet and Internet technologies. However these technologies have emphasized sharing and not security, despite the sensitive and private nature of much health information. Digital certificates (electronic documents which recognize an entity or its attributes) can be used to control access in clinical intranet applications. Objectives To outline the need for access control in distributed clinical database systems, to describe the use of digital certificates and security policies, and to propose the architecture for a system using digital certificates, cryptography and security policy to control access to clinical intranet applications. Methods We have previously developed a security policy, DIMEDAC (Distributed Medical Database Access Control), which is compatible with emerging public key and privilege management infrastructure. In our implementation approach we propose the use of digital certificates, to be used in conjunction with DIMEDAC. Results Our proposed access control system consists of two phases: the ways users gain their security credentials; and how these credentials are used to access medical data. Three types of digital certificates are used: identity certificates for authentication; attribute certificates for authorization; and access-rule certificates for propagation of access control policy. Once a user is identified and authenticated, subsequent access decisions are based on a combination of identity and attribute certificates, with access-rule certificates providing the policy framework. Conclusions Access control in clinical intranet applications can be successfully and securely managed through the use of digital certificates and the DIMEDAC security policy. PMID:11720951

Customized vaginal vault brachytherapy with computed tomography imaging-derived applicator prototyping.

PubMed

Wiebe, Ericka; Easton, Harry; Thomas, Gillian; Barbera, Lisa; D'Alimonte, Laura; Ravi, Ananth

2015-01-01

A novel customized vaginal brachytherapy mould technique has been developed for clinical use. This image-guided technique provides a brachytherapy applicator solution for irregular vaginal vault configuration and/or a wide vaginal apex relative to the vaginal introitus that would be sub-optimally treated with standard cylinders. The customized vaginal applicator is generated by the following process: CT images are obtained with contrast-soaked vaginal packing in situ to highlight unique anatomical detail. A 3-dimensional digital model is developed from the images and subsequently converted into a custom applicator with the use of stereolithography, which is an additive manufacturing technique whereby layers 50-100 μm thick of resin are deposited and polymerized using a laser to create intricate 3-dimensional objects. The density of the applicator and the dose delivered using the custom applicator were both measured to ensure accurate dosimetry. The CT-based densities of a clinical vaginal cylinder and the cylinder generated using stereolithography were 1.29 ± 0.06 g/cm(3) vs 1.28 ± 0.01 g/cm(3), respectively. The mean measured dose from a representative stereolithographed applicator normalized to dose measured for a single plastic catheter was 99.8 ± 4.2%. In patient dosimetric results indicate improved coverage of the lateral aspect of vaginal vault with the custom cylinder relative to the standard cylinder; 700 cGy vs 328 cGy, respectively, at a representative lateral vaginal dose point, while simultaneously achieving relatively narrow dose distribution in the anterior/posterior direction. Stereolithographic applicator production was available within a clinically acceptable timeframe, and its clinical feasibility and utility has been demonstrated. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2013-10-22

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5), which are of uncertain prognostic importance. In addition, for both the MI types, cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than using an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG), which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013. Published by Elsevier Inc.

Development of Clinical Trial Assessments for the Study of Interstitial Lung Disease in Patients who have Connective Tissue Diseases-Methodological Considerations.

PubMed

Huscher, Dörte; Saketkoo, Lesley Ann; Pittrow, David; Khanna, Dinesh

2010-05-01

This review article discusses the proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No consensus exists on measurement of disease activity or what constitutes a significant response to therapeutic interventions. Lack of appropriate measures inhibit effective drug development and hamper regulatory evaluation of candidate therapies.An interdisciplinary and international Steering Committee (SC) will oversee the execution of a 3-tier Delphi exercise involving experts in CTD and ILD. In parallel to the Delphi, qualitative information will be gathered from patients with ILD using focus groups. These data will subsequently be used to construct surveys to collect quantitative response from patients with ILD. The final Delphi and Patient Perspective results are to be scrutinized by SC and specialty sub-groups (including patient advocates) for truth, discrimination and feasibility - the OMERACT filters. Through application of Nominal Group technique, a core set of outcome measures will be proposed. Subsequent exercises will evaluate the applicability of a proposed core set to the unique issues posed by individual CTDs in addition to guidelines on screening, prognostication and damage scoring.

The influence of the Product Liability Act, governmental regulation, and medical economics on medical devices and their clinical applications.

PubMed

Hirose, T T

1996-12-01

The advancement of medical technology constantly demands the introduction of safer and more efficient medical instruments and devices. Recent litigation and rulings against the manufacturers of breast implants and the subsequent refusal of major plastic companies to supply materials to them are seriously threatening the production and development of other permanent implants such as ventricular assist devices and even disposable catheters. In addition, government overregulation also discourages and hinders production and clinical applications of new instruments. Current trends such as cost effectiveness measures and economic restraints imposed by government agencies and managed care systems are endangering investments from the medical and industrial communities to exploit more expensive and sophisticated instrument technologies. The resultant lack of grant money and pressure from animal rights advocates also suppress experimentation on primates and domestic laboratory animals.

[Research progress of mechanism and prevention of peritendinous adhesions].

PubMed

Jiang, Shichao; Liu, Shen; Fan, Cunyi

2013-05-01

To review the research progress of mechanism and prevention of peritendinous adhesions. Methods Recent literature about peritendinous adhesions was reviewed, and the results from experiments about the mechanism and prevention of peritendinous adhesions were analyzed. The molecular mechanism of peritendinous adhesions is related to overexpressions of transforming growth factor beta 1, early growth response protein 1, matrix metallopeptidase 9, and so on. The present methods of prevention of peritendinous adhesions include drugs, barrier, optimizing rehabilitation, gene therapy, and so on. These methods have achieved good results in experiments, but the clinical applications have not been confirmed yet. It is necessary to pay more attention to the research of mechanism of peritendinous adhesions and methods of its prevention and subsequently to convert them into clinical applications, which is significant to the prevention of peritendinous adhesions in the future.

Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement

PubMed Central

MacPherson, Hugh; Altman, Douglas G; Hammerschlag, Richard; Li, Youping; Wu, Taixiang; White, Adrian; Moher, David

2010-01-01

The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes 6 items and 17 subitems. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word ‘controlled’ in STRICTA is replaced by ‘clinical’, to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA checklist, in conjunction with both the main CONSORT statement and extension for non-pharmacological treatment, will raise the quality of reporting of clinical trials of acupuncture. PMID:20615861

Summary report of the First International Workshop on PET/MR imaging, March 19-23, 2012, Tübingen, Germany.

PubMed

Bailey, Dale L; Barthel, Henryk; Beyer, Thomas; Boellaard, Ronald; Gückel, Brigitte; Hellwig, Dirk; Herzog, Hans; Pichler, Bernd J; Quick, Harald H; Sabri, Osama; Scheffler, Klaus; Schlemmer, Heinz P; Schwenzer, Nina F; Wehrl, Hans F

2013-08-01

We report from the First International Workshop on positron emission tomography/magnetic resonance imaging (PET/MRI) that was organized by the University of Tübingen in March 2012. Approximately 100 imaging experts in MRI, PET and PET/computed tomography (CT), among them early adopters of pre-clinical and clinical PET/MRI technology, gathered from March 19 to 24, 2012 in Tübingen, Germany. The objective of the workshop was to provide a forum for sharing first-hand methodological and clinical know-how and to assess the potential of combined PET/MRI in various applications from pre-clinical research to scientific as well as clinical applications in humans. The workshop was comprised of pro-active sessions including tutorials, specific discussion panels and grand rounds. Pre-selected experts moderated the sessions, and feedback from the subsequent discussions is presented here to a greater readership. Naturally, the summaries provided herein are subjective descriptions of the hopes and challenges of PET/MR imaging as seen by the workshop attendees at a very early point in time of adopting PET/MRI technology and, as such, represent only a snapshot of current approaches.

Current directions in non-invasive low intensity electric brain stimulation for depressive disorder.

PubMed

Schutter, Dennis J L G; Sack, Alexander T

2014-01-01

Non-invasive stimulation of the human brain to improve depressive symptoms is increasingly finding its way in clinical settings as a viable form of somatic treatment. Following successful modulation of neural excitability with subsequent antidepressant effects, neural polarization by administrating weak direct currents to the scalp has gained renewed interest. A new wave of basic and clinical studies seems to underscore the potential therapeutic value of direct current stimulation in the treatment of depression. Issues concerning the lack of mechanistic insights into the workings of modifying brain function through neural polarization and how this process translates to its antidepressant properties calls for additional research. The range of its clinical applicability has yet to be established.

Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter?

PubMed

Satalkar, Priya; Elger, Bernice Simone; Shaw, David M

2016-10-01

Nanotechnology, which involves manipulation of matter on a 'nano' scale, is considered to be a key enabling technology. Medical applications of nanotechnology (commonly known as nanomedicine) are expected to significantly improve disease diagnostic and therapeutic modalities and subsequently reduce health care costs. However, there is no consensus on the definition of nanotechnology or nanomedicine, and this stems from the underlying debate on defining 'nano'. This paper aims to present the diversity in the definition of nanomedicine and its impact on the translation of basic science research in nanotechnology into clinical applications. We present the insights obtained from exploratory qualitative interviews with 46 stakeholders involved in translational nanomedicine from Europe and North America. The definition of nanomedicine has implications for many aspects of translational research including: fund allocation, patents, drug regulatory review processes and approvals, ethical review processes, clinical trials and public acceptance. Given the interdisciplinary nature of the field and common interest in developing effective clinical applications, it is important to have honest and transparent communication about nanomedicine, its benefits and potential harm. A clear and consistent definition of nanomedicine would significantly facilitate trust among various stakeholders including the general public while minimizing the risk of miscommunication and undue fear of nanotechnology and nanomedicine.

Prediction of clinical depression scores and detection of changes in whole-brain using resting-state functional MRI data with partial least squares regression

PubMed Central

Shimizu, Yu; Yoshimoto, Junichiro; Takamura, Masahiro; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2017-01-01

In diagnostic applications of statistical machine learning methods to brain imaging data, common problems include data high-dimensionality and co-linearity, which often cause over-fitting and instability. To overcome these problems, we applied partial least squares (PLS) regression to resting-state functional magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional representation that relates symptoms to brain activity and that predicts clinical measures. Our experimental results, based upon data from clinically depressed patients and healthy controls, demonstrated that PLS and its kernel variants provided significantly better prediction of clinical measures than ordinary linear regression. Subsequent classification using predicted clinical scores distinguished depressed patients from healthy controls with 80% accuracy. Moreover, loading vectors for latent variables enabled us to identify brain regions relevant to depression, including the default mode network, the right superior frontal gyrus, and the superior motor area. PMID:28700672

Postconditioning hormesis put in perspective: an overview of experimental and clinical studies.

PubMed

Wiegant, F A C; Prins, H A B; Van Wijk, R

2011-01-01

A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

Eyeing up the Future of the Pupillary Light Reflex in Neurodiagnostics

PubMed Central

Hall, Charlotte A.; Chilcott, Robert P.

2018-01-01

The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. Since these muscles are innervated by the parasympathetic and sympathetic nervous systems, respectively, different parameters of the PLR can be used as indicators for either sympathetic or parasympathetic modulation. Thus, the PLR provides an important metric of autonomic nervous system function that has been exploited for a wide range of clinical applications. Measurement of the PLR using dynamic pupillometry is now an established quantitative, non-invasive tool in assessment of traumatic head injuries. This review examines the more recent application of dynamic pupillometry as a diagnostic tool for a wide range of clinical conditions, varying from neurodegenerative disease to exposure to toxic chemicals, as well as its potential in the non-invasive diagnosis of infectious disease. PMID:29534018

Medication discrepancies associated with subsequent pharmacist-performed medication reconciliations in an ambulatory clinic.

PubMed

Philbrick, Ann M; Harris, Ila M; Schommer, Jon C; Fallert, Christopher J

2015-01-01

To describe the number of medication discrepancies associated with subsequent medication reconciliations by a clinical pharmacist in an ambulatory family medicine clinic and the proportion of subsequent medication reconciliation visits that were associated with hospital discharge, long-term anticoagulation management, or both. Data on medication reconciliations were collected over a 2-year time period in an ambulatory family medicine clinic for patients taking 10 or more medications. Medication reconciliation was performed 752 times for 500 patients. A total of 5,046 discrepancies were identified, with more than one-half deemed clinically important. A mean (± SD) of 6.7 ± 4.6 discrepancies per visit (3.5 ± 3.2 clinically important) were identified. The findings showed that the distribution of total discrepancies identified by pharmacist-performed medication reconciliation was significantly different over the course of subsequent medication reconciliations. However, the distribution of clinically important discrepancies was not significantly different; important discrepancies were as likely to be found in later reconciliations as in earlier ones. As subsequent medication reconciliation visits were performed, an increasing proportion consisted of post-hospital discharge visits, long-term anticoagulation managed by a clinical pharmacist, or both. Patients with a recent hospital discharge, on long-term anticoagulation management, or both, were more likely to have multiple sessions with a clinical pharmacist for medication reconciliation. These findings can help identify patients for whom medication reconciliation is warranted.

Structural properties of fracture haematoma: current status and future clinical implications.

PubMed

Wang, Xin; Friis, Thor; Glatt, Vaida; Crawford, Ross; Xiao, Yin

2017-10-01

Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Polyaniline-graphene based α-amylase biosensor with a linear dynamic range in excess of 6 orders of magnitude.

PubMed

Teixeira, Sofia Rodrigues; Lloyd, Catherine; Yao, Seydou; Andrea Salvatore Gazze; Whitaker, Iain S; Francis, Lewis; Conlan, R Steven; Azzopardi, Ernest

2016-11-15

α-amylase is an established marker for diagnosis of pancreatic and salivary disease, and recent research has seen a substantial expansion of its use in therapeutic and diagnostic applications for infection, cancer and wound healing. The lack of bedside monitoring devices for α-amylase detection has hitherto restricted the clinical progress of such applications. We have developed a highly sensitive α-amylase immunosensor platform, produced via in situ electropolymerization of aniline onto a screen-printed graphene support (SPE). Covalently binding an α-amylase specific antibody to a polyaniline (PANI) layer and controlling device assembly using electrochemical impedance spectroscopy (EIS), we have achieved a highly linear response against α-amylase concentration. Each stage of the assembly was characterized using a suite of high-resolution topographical, chemical and mechanical techniques. Quantitative, highly sensitive detection was demonstrated using an artificially spiked human blood plasma samples. The device has a remarkably wide limit of quantification (0.025-1000IU/L) compared to α-amylase assays in current clinical use. With potential for simple scale up to volume manufacturing though standard semiconductor production techniques and subsequently clinical application, this biosensor will enable clinical benefit through early disease detection, and better informed administration of correct therapeutic dose of drugs used to treat α-amylase related diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

Prescott, Jeffrey William

2013-02-01

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

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

NASA Astrophysics Data System (ADS)

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-10-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

HEMATOPOIETIC STEM CELL GENE THERAPY: ASSESSING THE RELEVANCE OF PRE-CLINICAL MODELS

PubMed Central

Larochelle, Andre; Dunbar, Cynthia E.

2013-01-01

The modern laboratory mouse has become a central tool for biomedical research with a notable influence in the field of hematopoiesis. Application of retroviral-based gene transfer approaches to mouse hematopoietic stem cells (HSCs) has led to a sophisticated understanding of the hematopoietic hierarchy in this model. However, the assumption that gene transfer methodologies developed in the mouse could be similarly applied to human HSCs for the treatment of human diseases left the field of gene therapy in a decade-long quandary. It is not until more relevant humanized xenograft mouse models and phylogenetically related large animal species were used to optimize gene transfer methodologies that unequivocal clinical successes were achieved. However, the subsequent reporting of severe adverse events in these clinical trials casted doubts on the predictive value of conventional pre-clinical testing, and encouraged the development of new assays for assessing the relative genotoxicity of various vector designs. PMID:24014892

PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas.

PubMed

Wang, Yi; Wu, Ling; Tian, Chen; Zhang, Yizhuo

2018-02-01

Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas. In this review, we outline the rationale for investigation of PD-1-PD-L1 immune-checkpoint blockade in lymphomas and discuss their prospect of applications in clinical treatment.

Implementation of an iPhone as a wireless accelerometer for quantifying gait characteristics.

PubMed

Lemoyne, Robert; Mastroianni, Timothy; Cozza, Michael; Coroian, Cristian; Grundfest, Warren

2010-01-01

The capacity to quantify and evaluate gait beyond the general confines of a clinical environment under effectively autonomous conditions may alleviate rampant strain on limited and highly specialized medical resources. An iPhone consists of a three dimensional accelerometer subsystem with highly robust and scalable software applications. With the synthesis of the integral iPhone features, an iPhone application, which constitutes a wireless accelerometer system for gait quantification and analysis, has been tested and evaluated in an autonomous environment. The acquired gait cycle data was transmitted wireless and through email for subsequent post-processing in a location remote to the location where the experiment was conducted. The iPhone application functioning as a wireless accelerometer for the acquisition of gait characteristics has demonstrated sufficient accuracy and consistency.

The Clinical Application of Mastectomy With Single Incision Followed by Immediate Laparoscopic-Assisted Breast Reconstruction With Latissimus Dorsi Muscle Flap.

PubMed

Yuan, Huozhong; Xie, Donghua; Xiao, Xigang; Huang, Xingwei

2017-08-01

To explore the clinical application of mastectomy with single incision followed by immediate laparoscopic-assisted breast reconstruction with latissimus dorsi muscle flap. Fifteen women with primary early breast cancer, 3 women with breast ductal carcinoma in situ, and 7 women with severe plasma cell mastitis were treated with partial mastectomy or total mastectomy, sentinel lymph node biopsy, or axillary lymph node dissection through a breast lateral transverse incision. Subsequent breast reconstruction with latissimus dorsi muscle flap was assisted by laparoscopy. The patient's position, time used in dissecting latissimus dorsi muscle flap, size of latissimus dorsi muscle flap, postoperative complications, and the cosmetic results after reconstruction were assessed. All the operations were well done through the breast lateral transverse incision and assistance of laparoscopy. The patient's position was changed only once during the operation. It took 1.5 to 2 hours to dissect latissimus dorsi muscle flap. The sizes of the latissimus dorsi muscle flap were 5 to 8 × 12 to 16 cm. There were no serious postoperative complications noted. The patients were satisfied with the appearance of the breasts and the small surgical scar. The surgical approach introduced is minimally invasive with concealed scar and outstanding cosmetic results. It is worth promoting in clinical application.

Can physicians recognize their own patients in de-identified notes?

PubMed

Meystre, Stéphane; Shen, Shuying; Hofmann, Deborah; Gundlapalli, Adi

2014-01-01

The adoption of Electronic Health Records is growing at a fast pace, and this growth results in very large quantities of patient clinical information becoming available in electronic format, with tremendous potentials, but also equally growing concern for patient confidentiality breaches. De-identification of patient information has been proposed as a solution to both facilitate secondary uses of clinical information, and protect patient information confidentiality. Automated approaches based on Natural Language Processing have been implemented and evaluated, allowing for much faster text de-identification than manual approaches. A U.S. Veterans Affairs clinical text de-identification project focused on investigating the current state of the art of automatic clinical text de-identification, on developing a best-of-breed de-identification application for clinical documents, and on evaluating its impact on subsequent text uses and the risk for re-identification. To evaluate this risk, we de-identified discharge summaries from 86 patients using our 'best-of-breed' text de-identification application with resynthesis of the identifiers detected. We then asked physicians working in the ward the patients were hospitalized in if they could recognize these patients when reading the de-identified documents. Each document was examined by at least one resident and one attending physician, and with 4.65% of the documents, physicians thought they recognized the patient because of specific clinical information, but after verification, none was correctly re-identified.

RECTAL-SPECIFIC MICROBICIDE APPLICATOR: EVALUATION AND COMPARISON WITH A VAGINAL APPLICATOR USED RECTALLY

PubMed Central

Carballo-Diéguez, Alex; Giguere, Rebecca; Dolezal, Curtis; Bauermeister, José; Leu, Cheng-Shiun; Valladares, Juan; Rohan, Lisa C.; Anton, Peter A.; Cranston, Ross D.; Febo, Irma; Mayer, Kenneth; McGowan, Ian

2014-01-01

An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1–10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p= ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p=0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems. PMID:24858481

Applications of ultrasensitive magnetic measurement technologies (invited) (abstract)

NASA Astrophysics Data System (ADS)

Hirschkoff, Eugene C.

1993-05-01

The development of reliable, easy-to-use magnetic measurement systems with significantly enhanced levels of sensitivity has opened up a number of broad new areas of application for magnetic sensing. Magnetometers based on optical pumping offer sensitivities at the picotesla level, while those that utilize superconducting quantum interference devices can operate at the femtotesla level. These systems are finding applications in areas as diverse as geophysical exploration, communications, and medical diagnostics. This review briefly surveys the capabilities and application areas for a number of magnetic sensing technologies. The emphasis then focuses on the application of the most sensitive of these to the field of medical diagnostics and functional imaging. Protocols for specific applications to noninvasive presurgical planning and to the noninvasive assay of cortical dysfunction in diseases ranging from epilepsy to migraine and schizophrenia will be described in detail. Data will be presented reporting independent validation of these techniques in ten patients who subsequently underwent surgery. Routine and reliable utilization of this ultrasensitive magnetic sensing technology in the clinic is now feasible and practical.

Integrating statistical and clinical research elements in intervention-related grant applications: summary from an NIMH workshop.

PubMed

Sherrill, Joel T; Sommers, David I; Nierenberg, Andrew A; Leon, Andrew C; Arndt, Stephan; Bandeen-Roche, Karen; Greenhouse, Joel; Guthrie, Donald; Normand, Sharon-Lise; Phillips, Katharine A; Shear, M Katherine; Woolson, Robert

2009-01-01

The authors summarize points for consideration generated in a National Institute of Mental Health (NIMH) workshop convened to provide an opportunity for reviewers from different disciplines-specifically clinical researchers and statisticians-to discuss how their differing and complementary expertise can be well integrated in the review of intervention-related grant applications. A 1-day workshop was convened in October, 2004. The workshop featured panel presentations on key topics followed by interactive discussion. This article summarizes the workshop and subsequent discussions, which centered on topics including weighting the statistics/data analysis elements of an application in the assessment of the application's overall merit; the level of statistical sophistication appropriate to different stages of research and for different funding mechanisms; some key considerations in the design and analysis portions of applications; appropriate statistical methods for addressing essential questions posed by an application; and the role of the statistician in the application's development, study conduct, and interpretation and dissemination of results. A number of key elements crucial to the construction and review of grant applications were identified. It was acknowledged that intervention-related studies unavoidably involve trade-offs. Reviewers are helped when applications acknowledge such trade-offs and provide good rationale for their choices. Clear linkage among the design, aims, hypotheses, and data analysis plan and avoidance of disconnections among these elements also strengthens applications. The authors identify multiple points to consider when constructing intervention-related grant applications. The points are presented here as questions and do not reflect institute policy or comprise a list of best practices, but rather represent points for consideration.

Cryostimulation improves recovery from oropharyngeal dysphagia after stroke

PubMed Central

Zart, Patrícia; Levy, Deborah Salle; Bolzan, Geovana de Paula; Mancopes, Renata; da Silva, Ana Maria Toniolo

2013-01-01

Summary Introduction: Stroke is considered one of the most frequent neurological causes of oropharyngeal dysphagia. Aim: To determine the effect of cryostimulation on oropharyngeal sensitivity and, subsequently, on the swallowing reaction and premature escape of food in patients with neurogenic dysphagia after stroke. Methods: Clinical and experimental study. The study enrolled 7 adult subjects, 6 men and 1 woman ranging from 28 to 64 years of age, with a diagnosis of stroke and current oropharyngeal dysphagia without any other underlying disease. The selected subjects underwent speech-language pathology evaluation and videofluoroscopic assessment of the dysphagia. The subjects were then treated with cryostimulation consisting of 10 applications to each structure (anterior faucial pillar, posterior oropharyngeal wall, soft palate, and back tongue) 3 times a day (for a total of 30 daily applications per structure) for 4 consecutive days. The patients were then re-evaluated based on the same criteria. The pre- and post-cryostimulation results of the clinical and videofluoroscopic evaluations were analyzed descriptively and statistically using Student's t-test and Fisher's exact test. Results: Cryostimulation had beneficial effects on oropharyngeal sensitivity in 6 of the 7 subjects. There was also a significant improvement in swallowing and in the premature escape in six subjects. Conclusion: Cryostimulation increased sensitivity and subsequently improved the swallowing reaction and premature escape of food in patients with neurogenic dysphagia after stroke. These effects were evident by both speech-language pathology and videofluoroscopic evaluation. PMID:25991991

Fatherhood and depression: a review of risks, effects, and clinical application.

PubMed

Spector, Aaron Z

2006-10-01

This literature review attempted to compile a complete evaluation of the presentation, risks, and subsequent effects upon a family in relation to paternal depression. Clinical applications are reviewed as well. As with women, fathers will present with a dysphoric mood, but unlike their female counterparts, depressed men often experience a change in social behavior. Withdrawal from social situations, indecisiveness, cynicism, and an irritable mood are often found as hallmark signs of depression in the adult male. Life stress, or family stress and low social support, are risk factors associated with depression among fathers. Marital difficulties may be the most common trigger for first-time depression in husbands just as divorce amplifies depressive episodes, especially when children are involved. A variety of treatments have proven effective for depressed fathers including traditional psycho-dynamic, CBT, and group therapy. Therapy is effective when it can be initiated and continued but research repeatedly showed that men seek it out far less than women. Effective outreach programs to encourage treatment among depressed fathers are recommended.

Mesenchymal stem cell-based therapy in kidney transplantation.

PubMed

Chen, Cheng; Hou, Jianquan

2016-02-07

Kidney transplantation is the best treatment for end-stage renal disease, but its implementation is limited by organ shortage and immune rejection. Side effects of current immunosuppressive drugs, such as nephrotoxicity, opportunistic infection, and tumorigenic potential, influence long-term graft outcomes. In recent years, continued research and subsequent discoveries concerning the properties and potential utilization of mesenchymal stem cells (MSCs) have aroused considerable interest and expectations. Biological characteristics of MSCs, including multi-lineage differentiation, homing potential, paracrine effect and immunomodulation, have opened new horizons for applications in kidney transplantation. However, many studies have shown that the biological activity of MSCs depends on internal inflammatory conditions, and the safety and efficacy of the clinical application of MSCs remain controversial. This review summarizes the findings of a large number of studies and aims to provide an objective viewpoint based on a comprehensive analysis of the presently established benefits and obstacles of implementing MSC-based therapy in kidney transplantation, and to promote its clinical translation.

Clinical application of a tissue-cultured skin autograft: an alternative for the treatment of non-healing or slowly healing wounds?

PubMed

Zöller, Nadja; Valesky, Eva; Butting, Manuel; Hofmann, Matthias; Kippenberger, Stefan; Bereiter-Hahn, Jürgen; Bernd, August; Kaufmann, Roland

2014-01-01

The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied. Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface. Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin. Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin. The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.

Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

NASA Astrophysics Data System (ADS)

Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

2011-03-01

Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

PubMed Central

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

User Interface Considerations for Collecting Data at the Point of Care in the Tablet PC Computing Environment

PubMed Central

Silvey, Garry M.; Lobach, David F.; Macri, Jennifer M.; Hunt, Megan; Kacmaz, Roje O.; Lee, Paul P.

2006-01-01

Collecting clinical data directly from clinicians is a challenge. Many standard development environments designed to expedite the creation of user interfaces for electronic healthcare applications do not provide acceptable components for satisfying the requirements for collecting and displaying clinical data at the point of care on the tablet computer. Through an iterative design and testing approach using think-aloud sessions in the eye care setting, we were able to identify and resolve several user interface issues. Issues that we discovered and subsequently resolved included checkboxes that were too small to be selectable with a stylus, radio buttons that could not be unselected, and font sizes that were too small to be read at arm’s length. PMID:17238715

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

PubMed

Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

2017-02-01

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Impact of Nursing Students' Free-Clinic Experiences on Subsequent Professional Nursing Practice

ERIC Educational Resources Information Center

Bell, Christina Lynn

2017-01-01

Bachelors of Science Nursing students at a small liberal arts college in the upper Midwest volunteer with an instructor at a free clinic as part of their curriculum. This study's purpose was to identify the impact of nursing students' free-clinic experiences on their subsequent professional nursing practice and their ability to attend to: (a)…

Effect of CO2 laser on Class V cavities of human molar teeth under a scanning electron microscope.

PubMed

Watanabe, I; Lopes, R A; Brugnera, A; Katayama, A Y; Gardini, A E

1996-01-01

The purpose of this study was to evaluate the effects of CO2 laser on dentin of class V cavities of extracted human molar teeth using a scanning electron microscope. SEM showed a smooth area with concentric lines formed by melting with subsequent recrystallization of dentin, areas of granulation, vitrified surface, numerous cracks, and irregular areas of descamative dentin. These data indicate that CO2 laser (4 and 6 watts) produces dentin alterations and limit its clinical applications.

Novel platinum compounds and nanoparticles as anticancer agents.

PubMed

Sarkar, Arindam

2018-01-01

Since the approval of cisplatin in 1979, platinum-based drugs have been regularly used in cancer chemotherapy as a first-line treatment or with the combination of other nonplatinum drugs. Subsequent approval of second- and third-generation drugs such as carboplatin and oxaliplatin respectively, has widened the therapeutic achievement of platinum compounds. There are few other platinum drugs approved recently and many other new drugs as well as the formulations of the old ones are going through clinical trials now. Considering the astonishing achievement of these drugs, analyses on the overall scenario of the patent applications on platinum compounds have become the priority to the scientific community. This review summarizes the published patent applications on the novel platinum anticancer compounds from 2012 to 2017 (August).

Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease*

PubMed Central

Good, David M.; Zürbig, Petra; Argilés, Àngel; Bauer, Hartwig W.; Behrens, Georg; Coon, Joshua J.; Dakna, Mohammed; Decramer, Stéphane; Delles, Christian; Dominiczak, Anna F.; Ehrich, Jochen H. H.; Eitner, Frank; Fliser, Danilo; Frommberger, Moritz; Ganser, Arnold; Girolami, Mark A.; Golovko, Igor; Gwinner, Wilfried; Haubitz, Marion; Herget-Rosenthal, Stefan; Jankowski, Joachim; Jahn, Holger; Jerums, George; Julian, Bruce A.; Kellmann, Markus; Kliem, Volker; Kolch, Walter; Krolewski, Andrzej S.; Luppi, Mario; Massy, Ziad; Melter, Michael; Neusüss, Christian; Novak, Jan; Peter, Karlheinz; Rossing, Kasper; Rupprecht, Harald; Schanstra, Joost P.; Schiffer, Eric; Stolzenburg, Jens-Uwe; Tarnow, Lise; Theodorescu, Dan; Thongboonkerd, Visith; Vanholder, Raymond; Weissinger, Eva M.; Mischak, Harald; Schmitt-Kopplin, Philippe

2010-01-01

Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. PMID:20616184

Designing informed game-based rehabilitation tasks leveraging advances in virtual reality.

PubMed

Lange, Belinda; Koenig, Sebastian; Chang, Chien-Yen; McConnell, Eric; Suma, Evan; Bolas, Mark; Rizzo, Albert

2012-01-01

This paper details a brief history and rationale for the use of virtual reality (VR) technology for clinical research and intervention, and then focuses on game-based VR applications in the area of rehabilitation. An analysis of the match between rehabilitation task requirements and the assets available with VR technology is presented. Low-cost camera-based systems capable of tracking user behavior at sufficient levels for game-based virtual rehabilitation activities are currently available for in-home use. Authoring software is now being developed that aims to provide clinicians with a usable toolkit for leveraging this technology. This will facilitate informed professional input on software design, development and application to ensure safe and effective use in the rehabilitation context. The field of rehabilitation generally stands to benefit from the continual advances in VR technology, concomitant system cost reductions and an expanding clinical research literature and knowledge base. Home-based activity within VR systems that are low-cost, easy to deploy and maintain, and meet the requirements for "good" interactive rehabilitation tasks could radically improve users' access to care, adherence to prescribed training and subsequently enhance functional activity in everyday life in clinical populations.

Emerging Opportunities for Serotypes of Botulinum Neurotoxins

PubMed Central

Peng Chen, Zhongxing; Morris, J. Glenn; Rodriguez, Ramon L.; Shukla, Aparna Wagle; Tapia-Núñez, John; Okun, Michael S.

2012-01-01

Background: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in cholinergic transmission. Despite the multiplicity of botulinal serotypes (designated as types A through G), therapeutic preparations are currently only available for BoNT types A and B. However, other BoNT serotypes are under study for possible clinical use and new clinical indications; Objective: To review the current research on botulinum neurotoxin serotypes A-G, and to analyze potential applications within basic science and clinical settings; Conclusions: The increasing understanding of botulinal neurotoxin pathophysiology, including the neurotoxin’s effects on specific neuronal populations, will help us in tailoring treatments for specific diagnoses, symptoms and patients. Scientists and clinicians should be aware of the full range of available data involving neurotoxin subtypes A-G. PMID:23202312

Application of endovascular coiling and subsequent Onyx 34 embolization in anterior communicating artery aneurysms with adjacent hematoma.

PubMed

Fang, Yi-Bin; Li, Qiang; Yang, Peng-Fei; Zhang, Qi; Wu, Yi-Na; Feng, Zheng-Zhe; Huang, Qing-Hai; Xu, Yi; Liu, Jian-Min

2014-08-01

Small anterior communicating artery aneurysms with recurrent bleeding and adjacent hematoma may have a high risk of post-operative rebleeding. This clinical study summarizes our preliminary experience with this subset of aneurysms, which were treated with endovascular coiling and subsequent Onyx 34 embolization. We retrospectively reviewed the data of 9 patients suffering from small anterior communicating artery aneurysms treated with the combination of coils and Onyx. The clinical characteristics, angiographic outcomes, and follow-up results are reviewed. Endovascular coiling and Onyx embolization were successfully accomplished in all 9 cases. The Raymond scale ratings of the treatments are all class I with the parent arteries kept patent. One patient died of severe brain edema on the 5th post-operative day. The modified Rankin scale (mRS) score for the other 8 patients at follow-ups (6m to 26m, 15.8m on average) was 0 in 5 cases, 1 in 2 cases, and 3 in 1 case. Seven of 8 patients (87.5%) underwent angiographic follow-up that demonstrated persistent durable occlusion with no recanalization. Endovascular coiling and subsequent Onyx 34 embolization may be effective in treating anterior communicating artery aneurysms with adjacent hematoma. Further studies with larger sample size and adequate follow-up are required to verify its safety and efficacy as well as to evaluate the long-term outcome. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and validation of an instrument to measure nurse educator perceived confidence in clinical teaching.

PubMed

Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

2017-12-01

Teaching nursing in clinical environments is considered complex and multi-faceted. Little is known about the role of the clinical nurse educator, specifically the challenges related to transition from clinician, or in some cases, from newly-graduated nurse to that of clinical nurse educator, as occurs in developing countries. Confidence in the clinical educator role has been associated with successful transition and the development of role competence. There is currently no valid and reliable instrument to measure clinical nurse educator confidence. This study was conducted to develop and psychometrically test an instrument to measure perceived confidence among clinical nurse educators. A multi-phase, multi-setting survey design was used. A total of 468 surveys were distributed, and 363 were returned. Data were analyzed using exploratory and confirmatory factor analyses. The instrument was successfully tested and modified in phase 1, and factorial validity was subsequently confirmed in phase 2. There was strong evidence of internal consistency, reliability, content, and convergent validity of the Clinical Nurse Educator Skill Acquisition Assessment instrument. The resulting instrument is applicable in similar contexts due to its rigorous development and validation process. © 2017 The Authors. Nursing & Health Sciences published by John Wiley & Sons Australia, Ltd.

Creating an effort tracking tool to improve therapeutic cancer clinical trials workload management and budgeting.

PubMed

James, Pam; Bebee, Patty; Beekman, Linda; Browning, David; Innes, Mathew; Kain, Jeannie; Royce-Westcott, Theresa; Waldinger, Marcy

2011-11-01

Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.

Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models.

PubMed

Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P

2012-01-01

In a phase III multi-center cancer clinical trial or a large public health study, sample size is predetermined to achieve desired power, and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date on the basis of the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment, and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B-38. The results showed that application of the proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.

Strain improvement by combined UV mutagenesis and ribosome engineering and subsequent fermentation optimization for enhanced 6'-deoxy-bleomycin Z production.

PubMed

Zhu, Xiangcheng; Kong, Jieqian; Yang, Hu; Huang, Rong; Huang, Yong; Yang, Dong; Shen, Ben; Duan, Yanwen

2018-02-01

The bleomycins (BLMs) are important clinical drugs extensively used in combination chemotherapy for the treatment of various cancers. Dose-dependent lung toxicity and the development of drug resistance have restricted their wide applications. 6'-Deoxy-BLM Z, a recently engineered BLM analogue with improved antitumor activity, has the potential to be developed into the next-generation BLM anticancer drug. However, its low titer in the recombinant strain Streptomyces flavoviridis SB9026 has hampered current efforts, which require sufficient compound, to pursue preclinical studies and subsequent clinical development. Here, we report the strain improvement by combined UV mutagenesis and ribosome engineering, as well as the fermentation optimization, for enhanced 6'-deoxy-BLM production. A high producer, named S. flavoviridis G-4F12, was successfully isolated, producing 6'-deoxy-BLM at above 70 mg/L under the optimized fermentation conditions, representing a sevenfold increase in comparison with that of the original producer. These findings demonstrated the effectiveness of combined empirical breeding methods in strain improvement and set the stage for sustainable production of 6'-deoxy-BLM via pilot-scale microbial fermentation.

7 CFR 3550.67 - Repayment period.

Code of Federal Regulations, 2010 CFR

2010-01-01

... loans, or subsequent loans made in conjunction with an assumption, if the applicant's adjusted income... repayment ability. (2) For subsequent loans not made in conjunction with an assumption if the applicant's...

20 CFR 404.2024 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 404.2022(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 416.624 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2012 CFR

2012-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 416.622(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 416.624 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2013 CFR

2013-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 416.622(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 404.2024 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2013 CFR

2013-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 404.2022(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 404.2024 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2012 CFR

2012-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 404.2022(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 416.624 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2014 CFR

2014-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 416.622(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

20 CFR 404.2024 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2014 CFR

2014-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... the payee applicant is a creditor of the beneficiary (see § 404.2022(d)). (b) Subsequent face-to-face interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews...

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

PubMed Central

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-01-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. PMID:27767027

Application of thoracic endovascular aortic repair (TEVAR) in treating dwarfism with Stanford B aortic dissection: A case report.

PubMed

Qiu, Jian; Cai, Wenwu; Shu, Chang; Li, Ming; Xiong, Qinggen; Li, Quanming; Li, Xin

2018-04-01

To apply thoracic endovascular aortic repair (TEVAR) to treat dwarfism complicated with Stanford B aortic dissection. In this report, we presented a 63-year-old male patient of dwarfism complicated with Stanford B aortic dissection successfully treated with TEVAR. He was diagnosed with dwarfism complicated with Stanford B aortic dissection. After conservative treatment, the male patient underwent TEVAR at 1 week after hospitalization. After operation, he presented with numbness and weakness of his bilateral lower extremities, and these symptoms were significantly mitigated after effective treatment. At 1- and 3-week after TEVAR, the aorta status was maintained stable and restored. The patient obtained favorable clinical prognosis and was smoothly discharged. During subsequent follow-up, he remained physically stable. TEVAR is probably an option for treating dwarfism complicated with Stanford B aortic dissection, which remains to be validated by subsequent studies with larger sample size.

Handheld single photon emission computed tomography (handheld SPECT) navigated video-assisted thoracoscopic surgery of computer tomography-guided radioactively marked pulmonary lesions.

PubMed

Müller, Joachim; Putora, Paul Martin; Schneider, Tino; Zeisel, Christoph; Brutsche, Martin; Baty, Florent; Markus, Alexander; Kick, Jochen

2016-09-01

Radioactive marking can be a valuable extension to minimally invasive surgery. The technique has been clinically applied in procedures involving sentinel lymph nodes, parathyroidectomy as well as interventions in thoracic surgery. Improvements in equipment and techniques allow one to improve the limits. Pulmonary nodules are frequently surgically removed for diagnostic or therapeutic reasons; here video-assisted thoracoscopic surgery (VATS) is the preferred technique. VATS might be impossible with nodules that are small or located deep in the lung. In this study, we examined the clinical application and safety of employing the newly developed handheld single photon emission tomography (handheld SPECT) device in combination with CT-guided radioactive marking of pulmonary nodules. In this pilot study, 10 subjects requiring surgical resection of a pulmonary nodule were included. The technique involved CT-guided marking of the target nodule with a 20-G needle, with subsequent injection of 25-30 MBq (effective: 7-14 MBq) Tc-99m MAA (Macro Albumin Aggregate). Quality control was made with conventional SPECT-CT to confirm the correct localization and exclude possible complications related to the puncture procedure. VATS was subsequently carried out using the handheld SPECT to localize the radioactivity intraoperatively and therefore the target nodule. A 3D virtual image was superimposed on the intraoperative visual image for surgical guidance. In 9 of the 10 subjects, the radioactive application was successfully placed directly in or in the immediate vicinity of the target nodule. The average size of the involved nodules was 9 mm (range 4-15). All successfully marked nodules were subsequently completely excised (R0) using VATS. The procedure was well tolerated. An asymptomatic clinically insignificant pneumothorax occurred in 5 subjects. Two subjects were found to have non-significant discrete haemorrhage in the infiltration canal of the needle. In a single subject, the radioactive marking was unsuccessful because the radioactivity spread into the pleural space. In our series of 10 patients, it was demonstrated that using handheld SPECT in conjunction with VATS to remove radioactively marked pulmonary nodules is feasible. The combination of proven surgical techniques with a novel localization device (handheld SPECT) allowed successful VATS excision of pulmonary nodules which, due to their localization and small size, would typically have required thoracotomy. ClinicalTrials.gov, NCT02050724, Public 01/29/214, Joachim Müller. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Evaluation of an integrated services program to prevent subsequent pregnancy and birth among urban teen mothers.

PubMed

Patchen, Loral; Letourneau, Kathryn; Berggren, Erica

2013-01-01

This article details the evaluation of a clinical services program for teen mothers in the District of Columbia. The program's primary objectives are to prevent unintended subsequent pregnancy and to promote contraceptive utilization. We calculated contraceptive utilization at 6, 12, 18, and 24 months after delivery, as well as occurrence of subsequent pregnancy and birth. Nearly seven in ten (69.5%) teen mothers used contraception at 24 months after delivery, and 57.1% of contraceptive users elected long-acting reversible contraception. In the 24-month follow-up period, 19.3% experienced at least one subsequent pregnancy and 8.0% experienced a subsequent birth. These results suggest that an integrated clinical services model may contribute to sustained contraceptive use and may prove beneficial in preventing subsequent teen pregnancy and birth.

Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

PubMed

Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; de Bono, Johann S; Small, Eric J; Shore, Neal D; Fizazi, Karim; Kheoh, Thian; Li, Jinhui; De Porre, Peter; Todd, Mary B; Yu, Margaret K; Ryan, Charles J

2017-07-01

In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Topical non-barrier agents for postoperative adhesion prevention in animal models.

PubMed

Imai, Atsushi; Suzuki, Noriko

2010-04-01

Pelvic adhesion can form as a result of inflammation, endometriosis or surgical trauma. Most surgical procedures performed by obstetrician-gynecologists are associated with pelvic adhesions that may cause subsequent serious sequelae, including small bowel obstruction, infertility, chronic pelvic pain, and difficulty in postoperative treatment, including complexity during subsequent surgical procedures. An increasing number of adhesion reduction agents, in the form of site-specific and broad-coverage barriers and solutions, are becoming available to surgical teams. The most widely studied strategies include placing synthetic barrier agents between the pelvic structures. Most of the adhesions in the barrier-treated patients develop in uncovered areas in the abdomen. This fact suggests that the application of liquid or gel anti-adhesive agents to cover all potential peritoneal lesions, together with the use of barrier agents, may reduce the formation of postoperative adhesions. This article introduces the topical choices available for adhesion prevention mentioned in preliminary clinical applications and animal models. To date there is no substantial evidence that their use reduces the incidence of postoperative adhesions. In combination with good surgical techniques, these non-barrier agents may play an important role in adhesion reduction. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper

PubMed Central

Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Börger, Verena; Buzas, Edit; Camussi, Giovanni; Chaput, Nathalie; Chatterjee, Devasis; Court, Felipe A.; del Portillo, Hernando A.; O'Driscoll, Lorraine; Fais, Stefano; Falcon-Perez, Juan M.; Felderhoff-Mueser, Ursula; Fraile, Lorenzo; Gho, Yong Song; Görgens, André; Gupta, Ramesh C.; Hendrix, An; Hermann, Dirk M.; Hill, Andrew F.; Hochberg, Fred; Horn, Peter A.; de Kleijn, Dominique; Kordelas, Lambros; Kramer, Boris W.; Krämer-Albers, Eva-Maria; Laner-Plamberger, Sandra; Laitinen, Saara; Leonardi, Tommaso; Lorenowicz, Magdalena J.; Lim, Sai Kiang; Lötvall, Jan; Maguire, Casey A.; Marcilla, Antonio; Nazarenko, Irina; Ochiya, Takahiro; Patel, Tushar; Pedersen, Shona; Pocsfalvi, Gabriella; Pluchino, Stefano; Quesenberry, Peter; Reischl, Ilona G.; Rivera, Francisco J.; Sanzenbacher, Ralf; Schallmoser, Katharina; Slaper-Cortenbach, Ineke; Strunk, Dirk; Tonn, Torsten; Vader, Pieter; van Balkom, Bas W. M.; Wauben, Marca; Andaloussi, Samir El; Théry, Clotilde; Rohde, Eva; Giebel, Bernd

2015-01-01

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed. PMID:26725829

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.

PubMed

Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Börger, Verena; Buzas, Edit; Camussi, Giovanni; Chaput, Nathalie; Chatterjee, Devasis; Court, Felipe A; Del Portillo, Hernando A; O'Driscoll, Lorraine; Fais, Stefano; Falcon-Perez, Juan M; Felderhoff-Mueser, Ursula; Fraile, Lorenzo; Gho, Yong Song; Görgens, André; Gupta, Ramesh C; Hendrix, An; Hermann, Dirk M; Hill, Andrew F; Hochberg, Fred; Horn, Peter A; de Kleijn, Dominique; Kordelas, Lambros; Kramer, Boris W; Krämer-Albers, Eva-Maria; Laner-Plamberger, Sandra; Laitinen, Saara; Leonardi, Tommaso; Lorenowicz, Magdalena J; Lim, Sai Kiang; Lötvall, Jan; Maguire, Casey A; Marcilla, Antonio; Nazarenko, Irina; Ochiya, Takahiro; Patel, Tushar; Pedersen, Shona; Pocsfalvi, Gabriella; Pluchino, Stefano; Quesenberry, Peter; Reischl, Ilona G; Rivera, Francisco J; Sanzenbacher, Ralf; Schallmoser, Katharina; Slaper-Cortenbach, Ineke; Strunk, Dirk; Tonn, Torsten; Vader, Pieter; van Balkom, Bas W M; Wauben, Marca; Andaloussi, Samir El; Théry, Clotilde; Rohde, Eva; Giebel, Bernd

2015-01-01

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Understanding clinical development of chimeric antigen receptor T cell therapies.

PubMed

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2017-06-01

In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype with promising efficacy in cancer treatment which are tested in many clinical trials, but have not yet received MAA. We generated an overview of the characteristics of CAR T-cell clinical development in the United States, Canada and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell products that proceeded to a subsequent clinical trial, used as a proxy for success, were compared with those that did not proceed. From the U.S. and European Union clinical trial databases, 106 CAR T-cell trials were selected, from which 49 were linked to a subsequent trial and 57 were not. The majority of the trials had an academic sponsor from which most did not proceed, whereas most commercially sponsored trials were followed by another clinical trial. Furthermore, trials with a subsequent trial more frequently recruited large patient cohorts and were more often multicenter compared with trials that were not followed up. These characteristics can be used by investigators to better design clinical trials with CAR T cells. We encourage sponsors to plan clinical development ahead for a higher efficiency of product development and thereby achieving a higher success rate of development towards MAA. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Multimodal magnetic nano-carriers for cancer treatment: Challenges and advancements

NASA Astrophysics Data System (ADS)

Aadinath, W.; Ghosh, Triroopa; Anandharamakrishnan, C.

2016-03-01

Iron oxide nanoparticles (IONPs) have been a propitious topic for cancer treatment in recent years because of its multifunctional theranostic applications under magnetic field. Two such widely used applications in cancer biology are gradient magnetic field guided targeting and alternative magnetic field (AMF) induced local hyperthermia. Gradient magnetic field guided targeting is a mode of active targeting of therapeutics conjugated with iron oxide nanoparticles. These particles also dissipate heat in presence of AMF which causes thermal injury to the cells of interest, for example tumour cells and subsequent death. Clinical trials divulge the feasibility of such magnetic nano-carrier as a promising candidate in cancer biology. However, these techniques need further investigations to curtail certain limitations manifested. Recent progresses in response have shrunken the barricade to certain extent. In this context, principles, challenges associated with these applications and recent efforts made in response will be discussed.

Experiences of engineering Grid-based medical software.

PubMed

Estrella, F; Hauer, T; McClatchey, R; Odeh, M; Rogulin, D; Solomonides, T

2007-08-01

Grid-based technologies are emerging as potential solutions for managing and collaborating distributed resources in the biomedical domain. Few examples exist, however, of successful implementations of Grid-enabled medical systems and even fewer have been deployed for evaluation in practice. The objective of this paper is to evaluate the use in clinical practice of a Grid-based imaging prototype and to establish directions for engineering future medical Grid developments and their subsequent deployment. The MammoGrid project has deployed a prototype system for clinicians using the Grid as its information infrastructure. To assist in the specification of the system requirements (and for the first time in healthgrid applications), use-case modelling has been carried out in close collaboration with clinicians and radiologists who had no prior experience of this modelling technique. A critical qualitative and, where possible, quantitative analysis of the MammoGrid prototype is presented leading to a set of recommendations from the delivery of the first deployed Grid-based medical imaging application. We report critically on the application of software engineering techniques in the specification and implementation of the MammoGrid project and show that use-case modelling is a suitable vehicle for representing medical requirements and for communicating effectively with the clinical community. This paper also discusses the practical advantages and limitations of applying the Grid to real-life clinical applications and presents the consequent lessons learned. The work presented in this paper demonstrates that given suitable commitment from collaborating radiologists it is practical to deploy in practice medical imaging analysis applications using the Grid but that standardization in and stability of the Grid software is a necessary pre-requisite for successful healthgrids. The MammoGrid prototype has therefore paved the way for further advanced Grid-based deployments in the medical and biomedical domains.

[Evaluation of the German Research Foundation's (GRF) »Clinical Trials Academy for Junior Researchers« - publications and funding profiles].

PubMed

Dahmen, Levka; Krummenauer, Frank

2016-11-01

Background | The »Clinical Trials Academy for Junior Researchers« is a strategic funding instrument of the German Research Foundation (GRF). In clinical research, this program responds to an increasing lack of qualified clinician scientists. Application for participation in the workshop is based on a self-proposed academy project; participants can furthermore apply for a GRF grant to implement this academy project. This evaluation should quantify publication and third-party-funding profiles after participation in one of the previous GRF junior researchers workshops on clinical trials. Methods | Participants of all four GRF workshops were addressed by a standardized questionnaire to consider the project related number of publications and the cumulative impact factor, as well as the cumulative project-related consequential third-party-funding. Results | 64 of 92 former participants took part in the survey. From 41 implemented projects, 32 were granted with initial financial support by the GRF. 27 publications with a cumulative impact factor of 130 impact factor points (IP) were published by 13 authors. Of the 21 persons who submitted a grant application for subsequent third-party-funding a cumulative total grant volume of 5 223 000 € was reported by 13 participants. Conclusion | Although only 13 out of 64 participants reported impact publications or third-party-funding, respectively, these junior researchers' output can be considered encouraging. © Georg Thieme Verlag KG Stuttgart · New York.

Comprehensive Psychopathological Assessment Based on the Association for Methodology and Documentation in Psychiatry (AMDP) System: Development, Methodological Foundation, Application in Clinical Routine, and Research.

PubMed

Stieglitz, Rolf-Dieter; Haug, Achim; Fähndrich, Erdmann; Rösler, Michael; Trabert, Wolfgang

2017-01-01

The documentation of psychopathology is core to the clinical practice of the psychiatrist and clinical psychologist. However, both in initial as well as further training and specialization in their fields, this particular aspect of their work receives scanty attention only. Yet, for the past 50 years, the Association for Methodology and Documentation in Psychiatry (AMDP) System has been in existence and available as a tool to serve precisely the purpose of offering a systematic introduction to the terminology and documentation of psychopathology. The motivation for its development was based on the need for an assessment procedure for the reliable documentation of the effectiveness of newly developed psychopharmacological substances. Subsequently, the AMDP-System began to be applied in the context of investigations into a number of methodological issues in psychiatry (e.g., the frequency and specificity of particular symptoms, the comparison of rating scales). The System then became increasingly important also in clinical practice and, today, represents the most used instrument for the documentation of psychopathology in the German-speaking countries of Europe. This paper intends to offer an overview of the AMDP-System, its origins, design, and functionality. After an initial account of the history and development of the AMDP-System, the discussion will in turn focus on the System's underlying methodological principles, the transfer of clinical skills and competencies in its practical application, and its use in research and clinical practice. Finally, potential future areas of development in relation to the AMDP-System are explored.

Comprehensive Psychopathological Assessment Based on the Association for Methodology and Documentation in Psychiatry (AMDP) System: Development, Methodological Foundation, Application in Clinical Routine, and Research

PubMed Central

Stieglitz, Rolf-Dieter; Haug, Achim; Fähndrich, Erdmann; Rösler, Michael; Trabert, Wolfgang

2017-01-01

The documentation of psychopathology is core to the clinical practice of the psychiatrist and clinical psychologist. However, both in initial as well as further training and specialization in their fields, this particular aspect of their work receives scanty attention only. Yet, for the past 50 years, the Association for Methodology and Documentation in Psychiatry (AMDP) System has been in existence and available as a tool to serve precisely the purpose of offering a systematic introduction to the terminology and documentation of psychopathology. The motivation for its development was based on the need for an assessment procedure for the reliable documentation of the effectiveness of newly developed psychopharmacological substances. Subsequently, the AMDP-System began to be applied in the context of investigations into a number of methodological issues in psychiatry (e.g., the frequency and specificity of particular symptoms, the comparison of rating scales). The System then became increasingly important also in clinical practice and, today, represents the most used instrument for the documentation of psychopathology in the German-speaking countries of Europe. This paper intends to offer an overview of the AMDP-System, its origins, design, and functionality. After an initial account of the history and development of the AMDP-System, the discussion will in turn focus on the System’s underlying methodological principles, the transfer of clinical skills and competencies in its practical application, and its use in research and clinical practice. Finally, potential future areas of development in relation to the AMDP-System are explored. PMID:28439242

Transportation Conditions for Prompt Use of Ex Vivo Expanded and Freshly Harvested Clinical-Grade Bone Marrow Mesenchymal Stromal/Stem Cells for Bone Regeneration

PubMed Central

Veronesi, Elena; Murgia, Alba; Caselli, Anna; Grisendi, Giulia; Piccinno, Maria Serena; Rasini, Valeria; Giordano, Rosaria; Montemurro, Tiziana; Bourin, Philippe; Sensebé, Luc; Rojewski, Markus T.; Schrezenmeier, Hubert; Layrolle, Pierre; Ginebra, Maria Pau; Panaitescu, Carmen Bunu; Gómez-Barrena, Enrique; Catani, Fabio; Paolucci, Paolo; Burns, Jorge S.

2014-01-01

Successful preliminary studies have encouraged a more translational phase for stem cell research. Nevertheless, advances in the culture of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) and osteoconductive qualities of combined biomaterials can be undermined if necessary cell transportation procedures prove unviable. We aimed at evaluating the effect of transportation conditions on cell function, including the ability to form bone in vivo, using procedures suited to clinical application. hBM-MSC expanded in current Good Manufacturing Practice (cGMP) facilities (cGMP-hBM-MSC) to numbers suitable for therapy were transported overnight within syringes and subsequently tested for viability. Scaled-down experiments mimicking shipment for 18 h at 4°C tested the influence of three different clinical-grade transportation buffers (0.9% saline alone or with 4% human serum albumin [HSA] from two independent sources) compared with cell maintenance medium. Cell viability after shipment was >80% in all cases, enabling evaluation of (1) adhesion to plastic flasks and hydroxyapatite tricalcium phosphate osteoconductive biomaterial (HA/β-TCP 3D scaffold); (2) proliferation rate; (3) ex vivo osteogenic differentiation in contexts of 2D monolayers on plastic and 3D HA/β-TCP scaffolds; and (4) in vivo ectopic bone formation after subcutaneous implantation of cells with HA/β-TCP scaffold into NOD/SCID mice. Von Kossa staining was used to assess ex vivo osteogenic differentiation in 3D cultures, providing a quantifiable test of 3D biomineralization ex vivo as a rapid, cost-effective potency assay. Near-equivalent capacities for cell survival, proliferation, and osteogenic differentiation were found for all transportation buffers. Moreover, cGMP-hBM-MSC transported from a production facility under clinical-grade conditions of 4% HSA in 0.9% saline to a destination 18 h away showed prompt adhesion to HA/β-TCP 3D scaffold and subsequent in vivo bone formation. A successfully validated transportation protocol extends the applicability of fresh stem cells involving multicentric trials for regenerative medicine. PMID:23845029

Effective progression of nuclear magnetic resonance-detected fragment hits.

PubMed

Eaton, Hugh L; Wyss, Daniel F

2011-01-01

Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrology.

PubMed

Gulati, Ashima; Somlo, Stefan

2018-05-01

The genesis of whole exome sequencing as a powerful tool for detailing the protein coding sequence of the human genome was conceptualized based on the availability of next-generation sequencing technology and knowledge of the human reference genome. The field of pediatric nephrology enriched with molecularly unsolved phenotypes is allowing the clinical and research application of whole exome sequencing to enable novel gene discovery and provide amendment of phenotypic misclassification. Recent studies in the field have informed us that newer high-throughput sequencing techniques are likely to be of high yield when applied in conjunction with conventional genomic approaches such as linkage analysis and other strategies used to focus subsequent analysis. They have also emphasized the need for the validation of novel genetic findings in large collaborative cohorts and the production of robust corroborative biological data. The well-structured application of comprehensive genomic testing in clinical and research arenas will hopefully continue to advance patient care and precision medicine, but does call for attention to be paid to its integrated challenges.

Hydrodynamic gene delivery in human skin using a hollow microneedle device.

PubMed

Dul, M; Stefanidou, M; Porta, P; Serve, J; O'Mahony, C; Malissen, B; Henri, S; Levin, Y; Kochba, E; Wong, F S; Dayan, C; Coulman, S A; Birchall, J C

2017-11-10

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Sorption of fibronectin to human root surfaces in vitro

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

Mendieta, C.; Caravana, C.; Fine, D.H.

1990-05-01

The purpose of this study was to determine the conditions that favor the sorption and retention of human plasma fibronectin to cementum. Rectangular root segments prepared from teeth extracted for orthodontic reasons were mounted on a capillary pipette and immersed in solutions of {sup 125}I fibronectin for assay of cementum sorption under various conditions. Kinetic studies showed sorption to be rapid, with 77% of the maximum fibronectin sorption occurring within 1 minute. Fibronectin sorption was reduced when added in conjunction with serum and was inhibited by monovalent ions (such as sodium), but enhanced in the presence of divalent cations (suchmore » as calcium). Exposure of cementum to serum partially blocked subsequent sorption of fibronectin, while cementum bound fibronectin was eluted by subsequent exposure to serum. Treatment of cementum with citric acid pH 1.1 (4 minutes) followed by 5% sodium hypochlorite (5 minutes) caused a significant increase in fibronectin sorption with maximum retention upon subsequent exposure to serum (P less than 0.05). Fibronectin sorption to cementum was: rapid, electrostatic in nature, competitive, reversible, Ca+(+)-facilitated, and maximized by prior treatment of the root with citric acid and sodium hypochlorite. It is concluded that sorption of fibronectin to cementum can be achieved for clinical gain; however, conditions of application can significantly influence both accumulation and subsequent release of root sorbed material.« less

Pressure application measurement (PAM): a novel behavioural technique for measuring hypersensitivity in a rat model of joint pain.

PubMed

Barton, Nicola J; Strickland, Iain T; Bond, Susan M; Brash, Harry M; Bate, Simon T; Wilson, Alex W; Chessell, Iain P; Reeve, Alison J; McQueen, Daniel S

2007-06-15

Chronic joint pain affects physical well being and can lead to severe psychological and social problems, therefore successful long-term management is highly sought-after. No current behavioural measures of pain used in pre-clinical models mimic the clinical dolorimeter, which provides an objective measure of joint hypersensitivity. In this study we aim to use a novel behavioural readout alongside an established measure to mimic the multifactorial measurements taken in the clinic. Using the pressure application measurement (PAM) device a gradually increasing squeeze was applied across the knee joint of rats until the animal gave an indication of pain or discomfort. PAM and the incapacitance tester were used to detect joint hypersensitivity in a well-established rodent model of adjuvant-induced arthritis. Subsequently, the analgesic effects of prednisolone (1, 3 or 10 mg kg(-1)), morphine (3 mg kg(-1)) and celecoxib (15 mg kg(-1)) were assessed. Both PAM and the incapacitance tester detected a reversal of hypersensitivity 1h post-drug administration. Furthermore, the two readouts were highly correlated, and power analysis indicated that PAM was highly reproducible. In conclusion, PAM provides a novel, accurate behavioural tool for detecting a primary mechanical hypersensitivity in a rat model of chronic inflammatory joint pain.

The emerging role of exercise testing and stress echocardiography in valvular heart disease.

PubMed

Picano, Eugenio; Pibarot, Philippe; Lancellotti, Patrizio; Monin, Jean Luc; Bonow, Robert O

2009-12-08

Exercise testing has an established role in the evaluation of patients with valvular heart disease and can aid clinical decision making. Because symptoms may develop slowly and indolently in chronic valve diseases and are often not recognized by patients and their physicians, the symptomatic, blood pressure, and electrocardiographic responses to exercise can help identify patients who would benefit from early valve repair or replacement. In addition, stress echocardiography has emerged as an important component of stress testing in patients with valvular heart disease, with relevant established and potential applications. Stress echocardiography has the advantages of its wide availability, low cost, and versatility for the assessment of disease severity. The versatile applications of stress echocardiography can be tailored to the individual patient with aortic or mitral valve disease, both before and after valve replacement or repair. Hence, exercise-induced changes in valve hemodynamics, ventricular function, and pulmonary artery pressure, together with exercise capacity and symptomatic responses to exercise, provide the clinician with diagnostic and prognostic information that can contribute to subsequent clinical decisions. Nevertheless, there is a lack of convincing evidence that the results of stress echocardiography lead to clinical decisions that result in better outcomes, and therefore large-scale prospective randomized studies focusing on patient outcomes are needed in the future.

A review of people who did not attend an epilepsy clinic and their clinical outcomes.

PubMed

Minshall, I; Neligan, A

2017-08-01

To review the clinical outcomes of people who failed to attend or failed subsequent follow up in a Primary Care based specialist epilepsy service. The case notes of 200 people who had failed to initially attend the service or subsequent follow up from 2005 to 2013 were reviewed. Clinical outcomes were determined for 152 people, with the remaining 48 having left the area. For those not attending at all, 64% had no further recorded events, a further 22% came under alternative specialist care and were managed appropriately, 6% were already in remission at the time of referral or at follow up and stayed seizure free. For people attending, but were subsequently lost to follow up, 78% were in remission, had improved seizure frequency, and normal pregnancies. In total 6% of those with poor control came under subsequent Neurological care. This study suggests that for the majority of people who fail to attend or are lost to follow up in a primary care specialist epilepsy clinic, the primary reasons appear to be that they had no further events, improved seizure control or that seizure remission has been achieved. The majority with persistent poor control came under Neurological care. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

PubMed Central

Hoffman, Michael D.

2015-01-01

Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

Recent advances in the application of metabolomics to Alzheimer's Disease.

PubMed

Trushina, Eugenia; Mielke, Michelle M

2014-08-01

The pathophysiological changes associated with Alzheimer's Disease (AD) begin decades before the emergence of clinical symptoms. Understanding the early mechanisms associated with AD pathology is, therefore, especially important for identifying disease-modifying therapeutic targets. While the majority of AD clinical trials to date have focused on anti-amyloid-beta (Aβ) treatments, other therapeutic approaches may be necessary. The ability to monitor changes in cellular networks that include both Aβ and non-Aβ pathways is essential to advance our understanding of the etiopathogenesis of AD and subsequent development of cognitive symptoms and dementia. Metabolomics is a powerful tool that detects perturbations in the metabolome, a pool of metabolites that reflects changes downstream of genomic, transcriptomic and proteomic fluctuations, and represents an accurate biochemical profile of the organism in health and disease. The application of metabolomics could help to identify biomarkers for early AD diagnosis, to discover novel therapeutic targets, and to monitor therapeutic response and disease progression. Moreover, given the considerable parallel between mouse and human metabolism, the use of metabolomics provides ready translation of animal research into human studies for accelerated drug design. In this review, we will summarize current progress in the application of metabolomics in both animal models and in humans to further understanding of the mechanisms involved in AD pathogenesis. © 2013.

Acute closed radial nerve injury

PubMed Central

Tuncel, Umut; Turan, Aydin; Kostakoglu, Naci

2011-01-01

We present a 45-year-old patient who had acute radial nerve palsy following a blunt trauma without any fracture or dislocation. He was injured by strucking in a combat three months ago. The patient has been followed by application of a long-arm plaster cast before referred to our clinic. Preoperative electromyoneurography and magnetic resonance imaging (MRI) indicated that there was a radial nerve injury on humeral groove. The British Medical Research Council (MRC) grade was 2/5 on his wrist preoperatively. The patient underwent an operation under general anesthesia. It was seen to be a second-degree nerve injury. The patient has subsequently regained full movement on his wrist and finger extension in six months. We suggest that a detailed clinical and electrodiagnostical evaluation is necessary in patients who have radial nerve injury when deciding the treatment, conservative or surgical. PMID:22347334

Clinical trial shows lasting function of a new moisturizing cream against vaginal dryness.

PubMed

Henneicke-von Zepelin, Hans-Heinrich; Williams, Ragna; Havemeister, Wiebke; Wigger-Alberti, Walter; Nolte, Klaus-Ulrich

2017-05-01

Vaginal dryness and associated symptoms may occur in women of any age and are a frequent burden after menopause. The North American Menopause Society recommends long-acting non-hormonal vaginal creams as first-line therapy. A new type of such creams was developed (Remifemin® FeuchtCreme in Austria and Germany). This hormone-free cream contains hamamelis virginiana distillate and well-established vaginal cream ingredients. We explored its physical function and tolerability in an open interventional clinical trial. 20 postmenopausal women (54 to 76 years, median 60) treated their vaginal dryness using this cream once daily for 7 days and reported about their symptoms before, 4 to 8 h after first and 14 to 22 h after last application. A physician assessed tolerability and local physical function. All patients completed the study. Local physical function significantly improved from dryness at baseline (mean 4.0 ± SD 1.8) to a normal moisture level, on average (6.3 ± 2.1 after first, 6.7 ± 2.1 after last application, p = 0.0001). Subjective assessment of a feeling vaginal dryness showed a significant improvement at both times (p = 0.0001). Onset and duration of feeling moisturized were reported to be 0 to 2 min and 11.3 ± 6.9 h after application. All women reported vaginal dryness at baseline. 55 and 80% of patients reported no dryness after first application and at the end of the investigation. The cream was seen at the application site for up to 21 h. Tolerability assessments did not reveal any relevant change over time. There were four adverse events in 4 patients, all not serious and of mild intensity: urinary urgency (2), diarrhoea (1) and mild spotting after first application (1). The latter was caused by the dry surface of the applicator and was avoided by moisturizing the surface of the applicator at subsequent applications. In conclusion, these study results indicate a well-tolerated and long-acting function of this new vaginal moisturizing cream. Further clinical research in more patients will follow.

Studies and applications of NiTi shape memory alloys in the medical field in China.

PubMed

Dai, K; Chu, Y

1996-01-01

The biomedical study of NiTi shape memory alloys has been undertaken in China since 1978. A series of stimulating corrosion tests, histological observations, toxicity tests, carcinogenicity tests, trace nickel elements analysis and a number of clinical trials have been conducted. The results showed that the NiTi shape memory alloy is a good biomaterial with good biocompatibility and no obvious local tissue reaction, carcinogenesis or erosion of implants were found experimentally or clinically. In 1981, on the basis of fundamental studies, a shape memory staple was used for the first time inside the human body. Subsequently, various shape memory devices were designed and applied clinically for internal fixation of fractures, spine surgery, endoprostheses, gynaecological and craniofacial surgery. Since 1990, a series of internal stents have been developed for the management of biliary, tracheal and esophageal strictures and urethrostenosis as well as vascular obturator for tumour management. Several thousand cases have been treated and had a 1-10 year follow-up and good clinical results with a rather low complication rate were obtained.

Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

PubMed Central

Sampaio, Hugo; Mowat, David; Roscioli, Tony

2017-01-01

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. PMID:28634552

Is tapentadol different from classical opioids? A review of the evidence

PubMed Central

Langford, Richard M; Knaggs, Roger; Farquhar-Smith, Paul; Dickenson, Anthony H

2016-01-01

Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids. PMID:27867511

Is tapentadol different from classical opioids? A review of the evidence.

PubMed

Langford, Richard M; Knaggs, Roger; Farquhar-Smith, Paul; Dickenson, Anthony H

2016-11-01

Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids.

Students' learning of clinical sonography: use of computer-assisted instruction and practical class.

PubMed

Wood, A K; Dadd, M J; Lublin, J R

1996-08-01

The application of information technology to teaching radiology will profoundly change the way learning is mediated to students. In this project, the integration of veterinary medical students' knowledge of sonography was promoted by a computer-assisted instruction program and a subsequent practical class. The computer-assisted instruction program emphasized the physical principles of clinical sonography and contained simulations and user-active experiments. In the practical class, the students used an actual sonographic machine for the first time and made images of a tissue-equivalent phantom. Students' responses to questionnaires were analyzed. On completing the overall project, 96% of the students said that they now understood sonographic concepts very or reasonably well, and 98% had become very or moderately interested in clinical sonography. The teaching and learning initiatives enhanced an integrated approach to learning, stimulated student interest and curiosity, improved understanding of sonographic principles, and contributed to an increased confidence and skill in using sonographic equipment.

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.

PubMed

Wetmore, James B; Mahnken, Jonathan D; Phadnis, Milind A

2016-09-21

Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis. We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified. Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved. Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.

Edited course of biomedical research: leaping forward with CRISPR.

PubMed

Collins, Patrick J; Hale, Christopher M; Xu, Han

2017-11-01

Within the short few years since the report of its application in precise genome editing, CRISPR technology has become the method of choice to modify and modulate gene expression in biomedical research and therapeutic development. Subsequently, a variety of research, diagnostic, and therapeutic tools have been developed based upon CRISPR's mechanism of action. Such tools have helped to deepen the understanding of fundamental biology and broaden the horizon in the search for treatments for diseases that have been considered hard or impossible to cure. As CRISPR technology advances closer to clinical applications, its short comings are becoming more apparent, thus creating opportunities to improve the technology's efficacy, specificity, and safety profile in this setting. We will summarize the current status of CRISPR technology and discuss its future impact in this review. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species.

PubMed

Springer, Jan; Goldenberger, Daniel; Schmidt, Friderike; Weisser, Maja; Wehrle-Wieland, Elisabeth; Einsele, Hermann; Frei, Reno; Löffler, Jürgen

2016-03-01

PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n = 17). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n = 10). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

A statistical metadata model for clinical trials' data management.

PubMed

Vardaki, Maria; Papageorgiou, Haralambos; Pentaris, Fragkiskos

2009-08-01

We introduce a statistical, process-oriented metadata model to describe the process of medical research data collection, management, results analysis and dissemination. Our approach explicitly provides a structure for pieces of information used in Clinical Study Data Management Systems, enabling a more active role for any associated metadata. Using the object-oriented paradigm, we describe the classes of our model that participate during the design of a clinical trial and the subsequent collection and management of the relevant data. The advantage of our approach is that we focus on presenting the structural inter-relation of these classes when used during datasets manipulation by proposing certain transformations that model the simultaneous processing of both data and metadata. Our solution reduces the possibility of human errors and allows for the tracking of all changes made during datasets lifecycle. The explicit modeling of processing steps improves data quality and assists in the problem of handling data collected in different clinical trials. The case study illustrates the applicability of the proposed framework demonstrating conceptually the simultaneous handling of datasets collected during two randomized clinical studies. Finally, we provide the main considerations for implementing the proposed framework into a modern Metadata-enabled Information System.

Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting

PubMed Central

Tschulik, Claudia; Piossek, Christine; Bet, Jeannette; Yamamoto, Tori N.; Schiemann, Matthias; Neuenhahn, Michael; Martin, Klaus; Schlapschy, Martin; Skerra, Arne; Schmidt, Thomas; Edinger, Matthias; Riddell, Stanley R.; Germeroth, Lothar; Busch, Dirk H.

2012-01-01

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research. PMID:22545138

Application of thoracic endovascular aortic repair (TEVAR) in treating dwarfism with Stanford B aortic dissection

PubMed Central

Qiu, Jian; Cai, Wenwu; Shu, Chang; Li, Ming; Xiong, Qinggen; Li, Quanming; Li, Xin

2018-01-01

Abstract Rationale: To apply thoracic endovascular aortic repair (TEVAR) to treat dwarfism complicated with Stanford B aortic dissection. Patient concerns: In this report, we presented a 63-year-old male patient of dwarfism complicated with Stanford B aortic dissection successfully treated with TEVAR. Diagnoses: He was diagnosed with dwarfism complicated with Stanford B aortic dissection. Interventions: After conservative treatment, the male patient underwent TEVAR at 1 week after hospitalization. After operation, he presented with numbness and weakness of his bilateral lower extremities, and these symptoms were significantly mitigated after effective treatment. At 1- and 3-week after TEVAR, the aorta status was maintained stable and restored. Outcomes: The patient obtained favorable clinical prognosis and was smoothly discharged. During subsequent follow-up, he remained physically stable. Lessons: TEVAR is probably an option for treating dwarfism complicated with Stanford B aortic dissection, which remains to be validated by subsequent studies with larger sample size. PMID:29703033

Personalized medicine: is it a pharmacogenetic mirage?

PubMed Central

Shah, Rashmi R; Shah, Devron R

2012-01-01

The notion of personalized medicine has developed from the application of the discipline of pharmacogenetics to clinical medicine. Although the clinical relevance of genetically-determined inter-individual differences in pharmacokinetics is poorly understood, and the genotype-phenotype association data on clinical outcomes often inconsistent, officially approved drug labels frequently include pharmacogenetic information concerning the safety and/or efficacy of a number of drugs and refer to the availability of the pharmacogenetic test concerned. Regulatory authorities differ in their approach to these issues. Evidence emerging subsequently has generally revealed the pharmacogenetic information included in the label to be premature. Revised drugs labels, together with a flurry of other collateral activities, have raised public expectations of personalized medicine, promoted as ‘the right drug at the right dose the first time.’ These expectations place the prescribing physician in a dilemma and at risk of litigation, especially when evidence-based information on genotype-related dosing schedules is to all intent and purposes non-existent and guidelines, intended to improve the clinical utility of available pharmacogenetic information or tests, distance themselves from any responsibility. Lack of efficacy or an adverse drug reaction is frequently related to non-genetic factors. Phenoconversion, arising from drug interactions, poses another often neglected challenge to any potential success of personalized medicine by mimicking genetically-determined enzyme deficiency. A more realistic promotion of personalized medicine should acknowledge current limitations and emphasize that pharmacogenetic testing can only improve the likelihood of diminishing a specific toxic effect or increasing the likelihood of a beneficial effect and that application of pharmacogenetics to clinical medicine cannot adequately predict drug response in individual patients. PMID:22591598

What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.

PubMed

Bakker, J L; Wever, K; van Waesberghe, J H; Beeker, A; Meijers-Heijboer, H; Konings, I R; Verheul, H M W

2015-12-01

Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line. Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data. Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit. The clinical benefit at first evaluation from systemic treatment in MBC does not predict for subsequent treatment benefit in this retrospective analysis. The fact that 61% of patients did not receive subsequent treatment after previous treatment failure suggests that either clinical judgement is of critical value in selection of patients to prevent them from unnecessary toxicity or, alternatively indicates that based on the assumption that prior treatment failure predicts for lack of benefit undertreatment of patients occurs. Therefore, a more adequate clinical judgement tool or predictive biomarkers for response are urgently needed to improve treatment outcome. Copyright © 2015. Published by Elsevier Ltd.

Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.

PubMed

Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

2015-09-25

Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects.

Clinical Application and Pharmacodynamic Monitoring of Apixaban in a Patient with End-Stage Renal Disease Requiring Chronic Hemodialysis.

PubMed

Kufel, Wesley D; Zayac, Adam S; Lehmann, David F; Miller, Christopher D

2016-11-01

Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy. © 2016 Pharmacotherapy Publications, Inc.

Capture and Genetic Analysis of Circulating Tumor Cells Using a Magnetic Separation Device (Magnetic Sifter).

PubMed

Ooi, Chin Chun; Park, Seung-Min; Wong, Dawson J; Gambhir, Sanjiv S; Wang, Shan X

2017-01-01

Circulating tumor cells (CTCs) are currently widely studied for their potential application as part of a liquid biopsy. These cells are shed from the primary tumor into the circulation, and are postulated to provide insight into the molecular makeup of the actual tumor in a minimally invasive manner. However, they are extremely rare in blood, with typical concentrations of 1-100 in a milliliter of blood; hence, a need exists for a rapid and high-purity method for isolating CTCs from whole blood. Here, we describe the application of a microfabricated magnetic sifter toward isolation of CTCs from whole blood at volumetric flow rates of 10 mL/h, along with the use of a PDMS-based nanowell system for single-cell gene expression profiling. This method allows rapid isolation of CTCs and subsequent integration with downstream genetic profiling methods for clinical applications such as targeted therapy, therapy monitoring, or further biological studies.

Cryopreservation of animal oocytes and embryos: Current progress and future prospects.

PubMed

Mandawala, A A; Harvey, S C; Roy, T K; Fowler, K E

2016-10-15

Cryopreservation describes techniques that permit freezing and subsequent warming of biological samples without loss of viability. The application of cryopreservation in assisted reproductive technology encompasses the freezing of gametes, embryos, and primordial germ cells. Whilst some protocols still rely on slow-freezing techniques, most now use vitrification, or ultra-rapid freezing, for both oocytes and embryos due to an associated decreased risk of damage caused by the lack of ice crystal formation, unlike in slow-freezing techniques. Vitrification has demonstrated its use in many applications, not only following IVF procedures in human embryology clinics but also following in vitro production of embryos in agriculturally important, or endangered animal species, before embryo transfer. Here, we review the various cryopreservation and vitrification technologies that are used in both humans and other animals and discuss the most recent innovations in vitrification with a particular emphasis on their applicability to animal embryology. Copyright © 2016 Elsevier Inc. All rights reserved.

Subsequent surgery rates after cervical total disc replacement using a Mobi-C Cervical Disc Prosthesis versus anterior cervical discectomy and fusion: a prospective randomized clinical trial with 5-year follow-up.

PubMed

Jackson, Robert J; Davis, Reginald J; Hoffman, Gregory A; Bae, Hyun W; Hisey, Michael S; Kim, Kee D; Gaede, Steven E; Nunley, Pierce Dalton

2016-05-01

OBJECTIVE Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion. The goal of this study was to evaluate subsequent surgery rates up to 5 years in patients treated with TDR or ACDF at 1 or 2 contiguous levels between C-3 and C-7. METHODS This was a prospective, multicenter, randomized, unblinded clinical trial. Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment. There were 260 patients in the 1-level study (179 TDR and 81 ACDF patients) and 339 patients in the 2-level study (234 TDR and 105 ACDF patients). RESULTS At 5 years, the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level (TDR, 4.5% [8/179]; ACDF, 17.3% [14/81]; p = 0.0012) and 2-level (TDR, 7.3% [17/234]; ACDF, 21.0% [22/105], p = 0.0007) treatment. The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts. CONCLUSIONS Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment. Clinical trial registration no.: NCT00389597 ( clinicaltrials.gov ).

[Advances of portable electrocardiogram monitor design].

PubMed

Ding, Shenping; Wang, Yinghai; Wu, Weirong; Deng, Lingli; Lu, Jidong

2014-06-01

Portable electrocardiogram monitor is an important equipment in the clinical diagnosis of cardiovascular diseases due to its portable, real-time features. It has a broad application and development prospects in China. In the present review, previous researches on the portable electrocardiogram monitors have been arranged, analyzed and summarized. According to the characteristics of the electrocardiogram (ECG), this paper discusses the ergonomic design of the portable electrocardiogram monitor, including hardware and software. The circuit components and software modules were parsed from the ECG features and system functions. Finally, the development trend and reference are provided for the portable electrocardiogram monitors and for the subsequent research and product design.

Evaluation of a deformable registration algorithm for subsequent lung computed tomography imaging during radiochemotherapy

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

Stützer, Kristin; Haase, Robert; Exner, Florian

2016-09-15

Purpose: Rating both a lung segmentation algorithm and a deformable image registration (DIR) algorithm for subsequent lung computed tomography (CT) images by different evaluation techniques. Furthermore, investigating the relative performance and the correlation of the different evaluation techniques to address their potential value in a clinical setting. Methods: Two to seven subsequent CT images (69 in total) of 15 lung cancer patients were acquired prior, during, and after radiochemotherapy. Automated lung segmentations were compared to manually adapted contours. DIR between the first and all following CT images was performed with a fast algorithm specialized for lung tissue registration, requiring themore » lung segmentation as input. DIR results were evaluated based on landmark distances, lung contour metrics, and vector field inconsistencies in different subvolumes defined by eroding the lung contour. Correlations between the results from the three methods were evaluated. Results: Automated lung contour segmentation was satisfactory in 18 cases (26%), failed in 6 cases (9%), and required manual correction in 45 cases (66%). Initial and corrected contours had large overlap but showed strong local deviations. Landmark-based DIR evaluation revealed high accuracy compared to CT resolution with an average error of 2.9 mm. Contour metrics of deformed contours were largely satisfactory. The median vector length of inconsistency vector fields was 0.9 mm in the lung volume and slightly smaller for the eroded volumes. There was no clear correlation between the three evaluation approaches. Conclusions: Automatic lung segmentation remains challenging but can assist the manual delineation process. Proven by three techniques, the inspected DIR algorithm delivers reliable results for the lung CT data sets acquired at different time points. Clinical application of DIR demands a fast DIR evaluation to identify unacceptable results, for instance, by combining different automated DIR evaluation methods.« less

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development.

PubMed

Heslop, Emma; Csimma, Cristina; Straub, Volker; McCall, John; Nagaraju, Kanneboyina; Wagner, Kathryn R; Caizergues, Didier; Korinthenberg, Rudolf; Flanigan, Kevin M; Kaufmann, Petra; McNeil, Elizabeth; Mendell, Jerry; Hesterlee, Sharon; Wells, Dominic J; Bushby, Kate

2015-04-23

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD.We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme.To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics.Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to market.

Application of best practice guidelines for OSCEs-An Australian evaluation of their feasibility and value.

PubMed

Mitchell, Marion L; Henderson, Amanda; Jeffrey, Carol; Nulty, Duncan; Groves, Michele; Kelly, Michelle; Knight, Sabina; Glover, Pauline

2015-05-01

Objective Structured Clinical Examinations (OSCEs) are widely used in health professional education and should be based on sound pedagogical foundations. The aim of this study is to evaluate the feasibility and utility of using Best Practice Guidelines (BPGs) within an OSCE format in a broad range of tertiary education settings with under-graduate and post-graduate nursing and midwifery students. We evaluated how feasible it was to apply the BPGs to modify OSCEs in a course; students' perspective of the OSCE; and finally, if the BPG-revised OSCEs better prepared students for clinical practice when compared with the original OSCEs. A mixed method with surveys, focus groups and semi-structured interviews evaluated the BPGs within an OSCE. Four maximally different contexts across four sites in Australia were used. Participants included lecturers and undergraduate nursing students in high and low fidelity simulation settings; under-graduate midwifery students; and post-graduate rural and remote area nursing students. 691 students participated in revised OSCEs. Surveys were completed by 557 students; 91 students gave further feedback through focus groups and 14 lecturers participated in interviews. At all sites the BPGs were successfully used to modify and implement OSCEs. Students valued the realistic nature of the modified OSCEs which contributed to students' confidence and preparation for clinical practice. The lecturers considered the revised OSCEs enhanced student preparedness for their clinical placements. The BPGs have a broad applicability to OSCEs in a wide range of educational contexts with improved student outcomes. Students and lecturers identified the revised OSCEs enhanced student preparation for clinical practice. Subsequent examination of the BPGs saw further refinement to a set of eight BPGs that provide a sequential guide to their application in a way that is consistent with best practice curriculum design principles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ultra-high definition (8K UHD) endoscope: our first clinical success.

PubMed

Yamashita, Hiromasa; Aoki, Hisae; Tanioka, Kenkichi; Mori, Toshiyuki; Chiba, Toshio

2016-01-01

We have started clinical application of 8K ultra-high definition (UHD; 7680 × 4320 pixels) imaging technology, which is a 16-fold higher resolution than the current 2K high-definition (HD; 1920 × 1080 pixels) technology, to an endoscope for advanced laparoscopic surgery. Based on preliminary testing experience and with subsequent technical and system improvements, we then proceeded to perform two cases of cholecystectomy and were able to achieve clinical success with an 8K UHD endoscopic system, which consisted of an 8K camera, a 30-degrees angled rigid endoscope with a lens adapter, a pair of 300-W xenon light sources, an 85-inch 8K LCD and an 8K video recorder. These experimental and clinical studies revealed the engineering and clinical feasibility of the 8K UHD endoscope, enabling us to have a positive outlook on its prospective use in clinical practice. The 8K UHD endoscopy promises to open up new possibilities for intricate procedures including anastomoses of thin nerves and blood vessels as well as more confident surgical resections of a diversity of cancer tissues. 8K endoscopic imaging, compared to imaging by the current 2K imaging technology, is very likely to lead to major changes in the future of medical practice.

An 'inflammatory' variant of solar purpura: a simulant of leukocytoclastic vasculitis and neutrophilic dermatoses.

PubMed

Wood, Benjamin A; LeBoit, Philip E

2013-08-01

To study the clinical and pathological features of cases of apparent solar purpura, with attention to the recently described phenomenon of inflammatory changes within otherwise typical lesions. We studied 95 cases diagnosed as solar purpura and identified 10 cases (10.5%) in which significant neutrophilic inflammation was present, potentially simulating a leukocytoclastic vasculitis or neutrophilic dermatosis. An additional three cases were identified in subsequent routine practice. The clinical features, including follow-up for subsequent development of vasculitis and histological features were studied. In all cases the histological features were typical of solar purpura, with the exception of inflammatory changes, typically associated with clefting of elastotic stroma. Clinical follow-up information was available for all patients and none developed subsequent evidence of a cutaneous or systemic vasculitis or neutrophilic dermatosis. Inflammatory changes appear to be more frequent in solar purpura than is generally recognised. Awareness of this histological variation and correlation with the clinical findings and evolution is important in avoiding misdiagnosis.

Current Concepts in Gastrointestinal Photodynamic Therapy

PubMed Central

Webber, John; Herman, Mark; Kessel, David; Fromm, David

1999-01-01

Objective To review current concepts of photodynamic therapy (PDT) applied to the treatment of tumors of the gastrointestinal tract. Summary Background Data PDT initially involves the uptake or production of a photosensitive compound by tumor cells. Subsequent activation of the photoreactive compound by a specific wavelength of light results in cell death, either directly or as a result of vascular compromise and/or apoptosis. Methods The authors selectively review current concepts relating to photosensitization, photoactivation, time of PDT application, tissue selectivity, sites of photodynamic action, PDT effects on normal tissue, limitations of PDT, toxicity of photosensitizers, application of principles of PDT to tumor detection, and current applications of PDT to tumors of the gastrointestinal tract. Results PDT is clearly effective for small cancers, but it is not yet clear in which cases such treatment is more effective than other currently acceptable approaches. The major side effect of PDT is cutaneous photosensitization. The major limitation of PDT is depth of tumor kill. As data from current and future clinical trials become available, a clearer perspective of where PDT fits in the treatment of cancers will be gained. Many issues regarding pharmacokinetic data of photosensitizers, newer technology involved in light sources, optimal treatment regimens that take advantage of the pharmacophysiology of photoablation, and light dosimetry still require solution. One can foresee application of differing sensitizers and light sources depending on the specific clinical situation. As technologic advances occur, interstitial PDT may have significant application. Conclusions PDT has a potentially important role either as a primary or adjuvant mode of treatment of tumors of the gastrointestinal tract. PMID:10400031

Thickened Endometrium in Postmenopausal Women With an Initial Biopsy of Limited, Benign, Surface Endometrium: Clinical Outcome and Subsequent Pathologic Diagnosis.

PubMed

Dermawan, Josephine K T; Hur, Christine; Uberti, Maria G; Flyckt, Rebecca; Falcone, Tommaso; Brainard, Jennifer; Abdul-Karim, Fadi W

2018-05-10

Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.

Regulatory considerations on new adjuvants and delivery systems.

PubMed

Sesardic, D

2006-04-12

New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

Technology support to a telehealth in the home service: Qualitative observations.

PubMed

Taylor, Alan; Wade, Victoria; Morris, Greg; Pech, Joanne; Rechter, Stuart; Kidd, Michael; Carati, Colin

2016-07-01

The Flinders University Telehealth in the Home (FTH) trial was an action research initiative that introduced and evaluated the impact of telehealth services on palliative care patients living in the community, home-based rehabilitation services for the elderly, and services to the elderly in residential aged care. The aim of this study was to understand the issues encountered during the provision of technology services that supported this trial. A mixed methods approach was undertaken to analyse the roles of information and communication technology (ICT) and clinical staff in design, technology management and training. The data sources were staff observations and documents including job logs, meetings, emails and technology descriptions. Use of consumer technology for telehealth required customisation of applications and services. Clinicians played a key role in definition of applications and the embedding of workflow into applications. Usability of applications was key to their subsequent use. Management of design creep and technology services, coupled with support and training for clinicians were important to maintenance of a telehealth service. In the setting described, an iterative approach to the development of telehealth services to the home using consumer technologies was needed. The efficient management of consumer devices in multiple settings will become critical as telehealth services grow in scale. Effective collaboration between clinical and technical stakeholders and further workforce education in telehealth can be key enablers for the transition of face-to-face care to a telehealth mode of delivery. © The Author(s) 2015.

From morphology to clinical pathophysiology: multiphoton fluorescence lifetime imaging at patients' bedside

NASA Astrophysics Data System (ADS)

Mess, Christian; Zens, Katharina; Gorzelanny, Christian; Metze, Dieter; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.; Huck, Volker

2017-02-01

Application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of skin diseases. By means of multiphoton excitation, endogenous biomolecules like NADH, collagen or elastin show autofluorescence or second harmonic generation. Thus, these molecules provide information about the subcellular morphology, epidermal architecture and physiological condition of the skin. To gain a deeper understanding of the linkage between cellular structure and physiological processes, non-invasive multiphotonbased intravital tomography (MPT) and fluorescence lifetime imaging (FLIM) were combined within the scopes of inflammatory skin, chronic wounds and drug delivery in clinical application. The optical biopsies generated via MPT were morphologically analyzed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Independent morphometric algorithms reliably showed a perinuclear accumulation in lesional skin in contrast to an even distribution in healthy skin. Confirmatively, MPT-FLIM showed an obvious metabolic shift in lesions. Moreover, detection of the onset and progression of inflammatory processes could be achieved. The feasibility of primary in vivo tracking of applied therapeutic agents further broadened our scope: We examined the permeation and subsequent distribution of agents directly visualized in patientś skin in short-term repetitive measurements. Furthermore, we performed MPT-FLIM follow-up investigations in the long-term course of therapy. Therefore, clinical MPT-FLIM application offers new insights into the pathophysiology and the individual therapeutic course of skin diseases, facilitating a better understanding of the processes of inflammation and wound healing.

The Doris Duke Clinical Scientist Development Award: implications for early-career physician scientists.

PubMed

Escobar-Alvarez, Sindy N; Myers, Elizabeth R

2013-11-01

The Doris Duke Charitable Foundation Clinical Scientist Development Award (CSDA) supports early-career physician scientists in their transition to independent research funding. The authors aimed to analyze the characteristics associated with success in CSDA competitions, determine whether attainment of a CSDA is associated with receiving subsequent research funding, and assess whether alumni remain in research. In 2011, the authors tested for associations between gender, age, race/ethnicity, academic degree, National Institutes of Health (NIH) funding rank of the applicant's institution, and success in CSDA competitions. They compared NIH R01 grant attainment, defined as the percentage of individuals who received at least one R01 grant, between CSDA alumni and highly ranked but unsuccessful CSDA applicants (1998-2007). Finally, the authors surveyed alumni to learn more about their professional activities. Demographic factors were not predictors of success in CSDA competitions; academic degree and funding rank of the applicant's institution, however, were. A greater percentage of CSDA alumni than nonalumni received at least one R01 grant (62% [74/120] versus 42% [44/105]). For CSDA alumni who were 10 or more years from the start of their award, their median percent effort toward research activities was 68%. The factors associated with success in a CSDA competition included a combined clinical and doctoral research degree and affiliation with a well-funded institution. More alumni received NIH independent research funding than those who applied but did not receive the award. Thus, the CSDA is associated with physicians establishing independent and recognized research careers.

Multiple mini-interview as a predictor of performance in the objective structured clinical examination among Physician Associates in the United Kingdom: a cohort study

PubMed Central

Kumar, Narendra; Bhardwaj, Shailaja; Rahman, Eqram

2018-01-01

Introduction Patient satisfaction and health care outcomes are directly linked to useful communication skills. Therefore, excellent interpersonal skills are imperative for health care professionals. Multiple mini-interview (MMI) is designed as a selection tool to assess the communication skills of applicants in medical schools during the admission process. However, objective structured clinical examination (OSCE) assesses students’ communication and clinical skills at the end of their academic terms. Recently, Anglia Ruskin University, Chelmsford, UK, adopted MMI in the selection process for the first cohort of MSc Physician Associate trainees for the academic year 2015–2016. This study aimed to determine the likelihood of MMI as a predictor of future performance of communication skills in the OSCE. Materials and methods The anonymous data of the average scores of communication skills attained in MMI and OSCE at the end of year 1 were collected for 30 students from the Physician Associate program team. Subsequently, Pearson’s correlation was computed to determine the relationship between the average scores of communication skills attained in MMI, and OSCE during trimester 2 and trimester 3 by the Physician Associate trainees. Results The study showed positive correlation between the scores of communication skills attained in MMI and OSCE during trimester 2 (r=0.956, n=30, p<0.001) and trimester 3 (r=0.966, n=30, p<0.001). Conclusion The study provides empirical evidence for the validity of MMI as a predictor of future performance of Physician Associate trainees’ communication skills during subsequent OSCEs. PMID:29695944

Multiple mini-interview as a predictor of performance in the objective structured clinical examination among Physician Associates in the United Kingdom: a cohort study.

PubMed

Kumar, Narendra; Bhardwaj, Shailaja; Rahman, Eqram

2018-01-01

Patient satisfaction and health care outcomes are directly linked to useful communication skills. Therefore, excellent interpersonal skills are imperative for health care professionals. Multiple mini-interview (MMI) is designed as a selection tool to assess the communication skills of applicants in medical schools during the admission process. However, objective structured clinical examination (OSCE) assesses students' communication and clinical skills at the end of their academic terms. Recently, Anglia Ruskin University, Chelmsford, UK, adopted MMI in the selection process for the first cohort of MSc Physician Associate trainees for the academic year 2015-2016. This study aimed to determine the likelihood of MMI as a predictor of future performance of communication skills in the OSCE. The anonymous data of the average scores of communication skills attained in MMI and OSCE at the end of year 1 were collected for 30 students from the Physician Associate program team. Subsequently, Pearson's correlation was computed to determine the relationship between the average scores of communication skills attained in MMI, and OSCE during trimester 2 and trimester 3 by the Physician Associate trainees. The study showed positive correlation between the scores of communication skills attained in MMI and OSCE during trimester 2 ( r =0.956, n=30, p <0.001) and trimester 3 ( r =0.966, n=30, p <0.001). The study provides empirical evidence for the validity of MMI as a predictor of future performance of Physician Associate trainees' communication skills during subsequent OSCEs.

[How to prevent tissue overgrowth and incrustation of metal stents in the urinary tract in patients with pelvic malignancy] b ].

PubMed

Marković, Z; Masulović, D; Markovic, B; Anojcić, P; Mladenović, A

2009-01-01

At the current level of stent application in urology each irreversible urostasis contraindicated for surgical therapy implies consideration of indications for metal stent insertion. Stent incrustation which leads directly into a new uroobstruction is a characteristic complication of this method. Available experience in different uroobstructive conditions has shown that very different clinical aspects of stent usage may directly determine the possibility of their incrustation. Stent incrustation may occur in the early postprocedural course or several months later. After that, prevention of stent incrustation starts with postprocedural evaluation, selection of the stent type, and it is subsequently continued by insertion technique and lasts practically permanently after the insertion (infection control, promotion of diuresis and maintenance of normal urodynamics). Authors present own experianse in clinical aplication of metal stents in uroradiology strictures for period of last 15 years.

Ceramic dental biomaterials and CAD/CAM technology: state of the art.

PubMed

Li, Raymond Wai Kim; Chow, Tak Wah; Matinlinna, Jukka Pekka

2014-10-01

Ceramics are widely used as indirect restorative materials in dentistry because of their high biocompatibility and pleasing aesthetics. The objective is to review the state of the arts of CAD/CAM all-ceramic biomaterials. CAD/CAM all-ceramic biomaterials are highlighted and a subsequent literature search was conducted for the relevant subjects using PubMed followed by manual search. Developments in CAD/CAM technology have catalyzed researches in all-ceramic biomaterials and their applications. Feldspathic glass ceramic and glass infiltrated ceramic can be fabricated by traditional laboratory methods or CAD/CAM. The advent of polycrystalline ceramics is a direct result of CAD/CAM technology without which the fabrication would not have been possible. The clinical uses of these ceramics have met with variable clinical success. Multiple options are now available to the clinicians for the fabrication of aesthetic all ceramic restorations. Copyright © 2014 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

The efficacy of two-stage titanium implants as orthodontic anchorage in the preprosthodontic correction of third molars in adults--a report of three cases.

PubMed

Haanaes, H R; Stenvik, A; Beyer-Olsen, E S; Tryti, T; Faehn, O

1991-08-01

Orthodontic movement of teeth is often required to satisfactorily treat a variety of oral rehabilitation problems. Considerable limitations in the clinical application of orthodontic treatment may result from the lack of teeth suitable for anchorage. Three patients with edentulous posterior segments are presented illustrating how implants can be utilized for preprosthodontic correction of impacted third molars rendering them suitable as bridge abutments. The patients have been followed for 8-10 years. Two-stage titanium implants were used as orthodontic anchorage as no dental anchorage was available. Edgewise orthodontic mechanics were used to move the third molars mesially with forces up to 2.5 N (about 250 g). No movement of the implants occurred and they were radiologically and clinically intact at the end of the orthodontic loading and were, therefore, subsequently used as bridge abutments.

An audit of inpatient case records and suggestions for improvements.

PubMed

Arshad, A R; Ganesananthan, S; Ajik, S

2000-09-01

A study was carried out in Kuala Lumpur Hospital to review the adequacy of documentation of bio-data and clinical data including clinical examination, progress review, discharge process and doctor's identification in ten of our clinical departments. Twenty criteria were assessed in a retrospective manner to scrutinize the contents of medical notes and subsequently two prospective evaluations were conducted to see improvement in case notes documentation. Deficiencies were revealed in all the criteria selected. However there was a statistically significant improvement in the eleven clinical data criteria in the subsequent two evaluations. Illegibility of case note entries and an excessive usage of abbreviations were noted during this audit. All clinical departments and hospitals should carry out detailed studies into the contents of their medical notes.

Institutionalizing telemedicine applications: the challenge of legitimizing decision-making.

PubMed

Zanaboni, Paolo; Lettieri, Emanuele

2011-09-28

During the last decades a variety of telemedicine applications have been trialed worldwide. However, telemedicine is still an example of major potential benefits that have not been fully attained. Health care regulators are still debating why institutionalizing telemedicine applications on a large scale has been so difficult and why health care professionals are often averse or indifferent to telemedicine applications, thus preventing them from becoming part of everyday clinical routines. We believe that the lack of consolidated procedures for supporting decision making by health care regulators is a major weakness. We aim to further the current debate on how to legitimize decision making about the institutionalization of telemedicine applications on a large scale. We discuss (1) three main requirements--rationality, fairness, and efficiency--that should underpin decision making so that the relevant stakeholders perceive them as being legitimate, and (2) the domains and criteria for comparing and assessing telemedicine applications--benefits and sustainability. According to these requirements and criteria, we illustrate a possible reference process for legitimate decision making about which telemedicine applications to implement on a large scale. This process adopts the health care regulators' perspective and is made up of 2 subsequent stages, in which a preliminary proposal and then a full proposal are reviewed.

CONGESTIVE HEART FAILURE ASSOCIATED WITH PREGNANCY IN OKAPI (OKAPIA JOHNSTONI).

PubMed

Warren, Joshua D; Aitken-Palmer, Copper; Weldon, Alan D; Flanagan, Joseph P; Howard, Lauren L; Garner, Michael M; Citino, Scott B

2017-03-01

Acute signs associated with cardiovascular disease occurred in three pregnant okapi ( Okapia johnstoni ) during early to midgestation and progressed to congestive heart failure. Congestive heart failure was diagnosed antemortem using echocardiography and plasma cardiac troponin levels. Clinical signs included decreased activity, hyporexia, tachypnea, dyspnea, flared nostrils, and productive coughing with copious amounts of foamy nasal discharge. Parenteral and oral treatment with furosemide, enalapril, and spironolactone controlled clinical signs in the three okapi allowing each to carry out one pregnancy to term. Two okapi carried the first pregnancy to term after showing signs, while one okapi aborted the first calf and gave birth to a healthy calf in a subsequent pregnancy. Subsequent pregnancy in one okapi ended with abortion and associated dystocia and endometritis. Following parturition, clinical signs associated with heart failure resolved in all three individuals; serial echocardiography in two individuals showed improvement in fractional shortening and left atrial size and all three okapi showed markedly decreased pleural effusion and resolution of pulmonary edema. However, subsequent pregnancies in all three okapi induced respiratory distress and recurrence of congestive heart failure; one okapi died from congestive heart failure associated with subsequent pregnancy. This case series describes the clinical presentation and pathologic findings of congestive heart failure during pregnancy in adult okapi.

Tissue engineering in urothelium regeneration.

PubMed

Vaegler, Martin; Maurer, Sabine; Toomey, Patricia; Amend, Bastian; Sievert, Karl-Dietrich

2015-03-01

The development of therapeutic treatments to regenerate urothelium, manufacture tissue equivalents or neourethras for in-vivo application is a significant challenge in the field of tissue engineering. Many studies have focused on urethral defects that, in most cases, inadequately address current therapies. This article reviews the primary tissue engineering strategies aimed at the clinical requirements for urothelium regeneration while concentrating on promising investigations in the use of grafts, cellular preparations, as well as seeded or unseeded natural and synthetic materials. Despite significant progress being made in the development of scaffolds and matrices, buccal mucosa transplants have not been replaced. Recently, graft tissues appear to have an advantage over the use of matrices. These therapies depend on cell isolation and propagation in vitro that require, not only substantial laboratory resources, but also subsequent surgical implant procedures. The choice of the correct cell source is crucial when determining an in-vivo application because of the risks of tissue changes and abnormalities that may result in donor site morbidity. Addressing an appropriately-designed animal model and relevant regulatory issues is of fundamental importance for the principal investigators when a therapy using cellular components has been developed for clinical use. Copyright © 2014 Elsevier B.V. All rights reserved.

Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

PubMed Central

Park, Soo-Jin; Im, Dong-Soon

2017-01-01

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P1–5. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications. PMID:28035084

How to adapt existing evidence-based clinical practice guidelines: a case example with smoking cessation guidelines in Canada

PubMed Central

Selby, Peter; Hunter, Katie; Rogers, Jess; Lang-Robertson, Kelly; Soklaridis, Sophie; Chow, Virginia; Tremblay, Michèle; Koubanioudakis, Denise; Dragonetti, Rosa; Hussain, Sarwar; Zawertailo, Laurie

2017-01-01

Objective To develop and encourage the adoption of clinical practice guidelines (CPGs) for smoking cessation in Canada by engaging stakeholders in the adaptation of existing high-quality CPGs using principles of the ADAPTE framework. Methods An independent expert body in guideline review conducted a review and identified six existing CPGs, which met a priori criteria for quality and potential applicability to the local context. Summary statements were extracted and assigned a grade of recommendation and level of evidence by a second expert panel. Regional knowledge exchange brokers recruited additional stakeholders to build a multidisciplinary network of over 800 clinicians, researchers and decision-makers from across Canada. This interprofessional network and other stakeholders were offered various opportunities to provide input on the guideline both online and in person. We actively encouraged end-user input into the development and adaptation of the guidelines to ensure applicability to various practice settings and to promote adoption. Results The final guideline contained 24 summary statements along with supporting clinical considerations, across six topic area sections. The guideline was adopted by various provincial/territorial and national government and non-governmental organisations. Conclusions This method can be applied in other jurisdictions to adapt existing high-quality smoking cessation CPGs to the local context and to facilitate subsequent adoption by various stakeholders. PMID:29102984

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis.

PubMed

Frost, Adaani E; Badesch, David B; Miller, Dave P; Benza, Raymond L; Meltzer, Leslie A; McGoon, Michael D

2013-11-01

Time to clinical worsening has been proposed as a primary end point in clinical trials of pulmonary arterial hypertension (PAH); however, neither standardized nor validated definitions of clinical worsening across PAH trials exist. This study aims to evaluate a proposed definition of clinical worsening within a large prospective, observational registry of patients with PAH with respect to its value as a predictor of proximate (within 1 year) risk for subsequent major events (ie, death, transplantation, or atrial septostomy). We assessed overall 2-year survival and survival free from major events to determine the relationship between clinical worsening and major events among adults with hemodynamically defined PAH (N = 3,001). Freedom from clinical worsening was defined as freedom from worsening functional class (FC), a ≥ 15% reduction in 6-min walk distance (6MWD), all-cause hospitalization, or the introduction of parenteral prostacyclin analog therapy. In the 2 years of follow-up, 583 patients died. Four hundred twenty-six died after a documented clinical worsening event, including FC worsening (n = 128), a ≥ 15% reduction in 6MWD (n = 118), all-cause hospitalization (n = 370), or introduction of a prostacyclin analog (n = 91). Patients who experienced clinical worsening had significantly poorer subsequent 1-year survival postworsening than patients who did not worsen (P < .001). Clinical worsening was highly predictive of subsequent proximate mortality in this analysis from an observational study. These results validate the use of clinical worsening as a meaningful prognostic tool in clinical practice and as a primary end point in clinical trial design. ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Identifying Opportunities for Vertical Integration of Biochemistry and Clinical Medicine.

PubMed

Wendelberger, Karen J.; Burke, Rebecca; Haas, Arthur L.; Harenwattananon, Marisa; Simpson, Deborah

1998-01-01

Objectives: Retention of basic science knowledge, as judged by National Board of Medical Examiners' (NBME) data, suffers due to lack of apparent relevance and isolation of instruction from clinical application, especially in biochemistry. However, the literature reveals no systematic process for identifying key biochemical concepts and associated clinical conditions. This study systematically identified difficult biochemical concepts and their common clinical conditions as a critical step towards enhancing relevance and retention of biochemistry.Methods: A multi-step/ multiple stakeholder process was used to: (1) identify important biochemistry concepts; (2) determine students' perceptions of concept difficulty; (3) assess biochemistry faculty, student, and clinical teaching scholars' perceived relevance of identified concepts; and (4) identify associated common clinical conditions for relevant and difficult concepts. Surveys and a modified Delphi process were used to gather data, subsequently analyzed using SPSS for Windows.Results: Sixteen key biochemical concepts were identified. Second year medical students rated 14/16 concepts as extremely difficult while fourth year students rated nine concepts as moderately to extremely difficult. On average, each teaching scholar generated common clinical conditions for 6.2 of the 16 concepts, yielding a set of seven critical concepts and associated clinical conditions.Conclusions: Key stakeholders in the instructional process struggle to identify biochemistry concepts that are critical, difficult to learn and associated with common clinical conditions. However, through a systematic process beginning with identification of concepts and associated clinical conditions, relevance of basic science instruction can be enhanced.

Clinical stages in patients with primary and subsequent cancers based on the czech cancer registry 1976-2005.

PubMed

Geryk, Edvard; Stampach, Radim; Dítě, Petr; Kozel, Jiří; Horváth, Teodor; Kubíček, Petr

2013-01-01

Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3-6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms.

Microtiter format for simultaneous multianalyte detection and development of a PCR-chemiluminescent enzyme immunoassay for typing human papillomavirus DNAs.

PubMed

Roda, Aldo; Mirasoli, Mara; Venturoli, Simona; Cricca, Monica; Bonvicini, Francesca; Baraldini, Mario; Pasini, Patrizia; Zerbini, Marialuisa; Musiani, Monica

2002-10-01

To allow multianalyte binding assays, we have developed a novel polystyrene microtiter plate containing 24 main wells, each divided into 7 subwells. We explored its clinical potential by developing a PCR-chemiluminescent immunoassay (PCR-CLEIA) for simultaneous detection and typing of seven high oncogenic risk human papillomavirus (HPV) DNAs in one well. Seven different oligonucleotide probes, each specific for a high-risk HPV genotype, were separately immobilized in the subwells. Subsequently, a digoxigenin-labeled consensus PCR amplification product was added to the main well. The PCR product hybridized to the immobilized probe corresponding to its genotype and was subsequently detected by use of a peroxidase-labeled anti-digoxigenin antibody and chemiluminescence imaging with an ultrasensitive charge-coupled device camera. Results obtained for 50 cytologic samples were compared with those obtained with a conventional colorimetric PCR-ELISA. The method was specific and allowed detection of 50 genome copies of HPV 16, 18, 33, and 58, and 100 genome copies of HPV 31, 35, and 45. Intra- and interassay CVs for the method were 5.6% and 7.9%, respectively. All results obtained for clinical samples were confirmed by the conventional PCR-ELISA. PCR-CLEIA allows rapid, single-tube simultaneous detection and typing of seven high-risk HPV DNAs with small reagent volumes. The principle appears applicable to the development of other single-tube panels of tests.

The burned ear; possibilities and challenges in framework reconstruction and coverage.

PubMed

Bos, E J; Doerga, P; Breugem, C C; van Zuijlen, P P

2016-11-01

Ear reconstruction remains a challenging procedure, especially in burn victims. The ear is particularly vulnerable to thermal injury because of its location and the thin integument. The thermal injury could subsequently include skin and the deeper located auricular cartilage framework. This type of injury could have long lasting mutilating effect not only because the ear's morphology is mainly related to this framework but also because it will not recover or regenerate once injured. Grafts of costal cartilage or synthetic materials might replace missing cartilage. However, the poor quality of the adjacent skin and subcutaneous tissues makes the reconstruction of a burned ear an even more daunting procedure than congenital or many oncologic indications. As such, regeneration of the skin will be the next step in reconstruction of the burned ear. There is still much development and research to be done, but encouraging results have been shown in tissue engineering of skin and cartilage. Furthermore, 3D (bio)printing of cartilage to facilitate reproduction of the ear's complex shape certainly has potential and might find an interesting role in ear reconstruction. In this review, different clinical challenges and options for ear reconstruction in burn patients are described. Subsequently, although still far from large scale clinical application, state of the art developments in the field of tissue engineering and 3D (bio)printing are also discussed. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Automatic Calculation of Hydrostatic Pressure Gradient in Patients with Head Injury: A Pilot Study.

PubMed

Moss, Laura; Shaw, Martin; Piper, Ian; Arvind, D K; Hawthorne, Christopher

2016-01-01

The non-surgical management of patients with traumatic brain injury is the treatment and prevention of secondary insults, such as low cerebral perfusion pressure (CPP). Most clinical pressure monitoring systems measure pressure relative to atmospheric pressure. If a patient is managed with their head tilted up, relative to their arterial pressure transducer, then a hydrostatic pressure gradient (HPG) can act against arterial pressure and cause significant errors in calculated CPP.To correct for HPG, the arterial pressure transducer should be placed level with the intracranial pressure transducer. However, this is not always achieved. In this chapter, we describe a pilot study investigating the application of speckled computing (or "specks") for the automatic monitoring of the patient's head tilt and subsequent automatic calculation of HPG. In future applications this will allow us to automatically correct CPP to take into account any HPG.

Circulating Tumor Cells: Moving Biological Insights into Detection

PubMed Central

Chen, Lichan; Bode, Ann M; Dong, Zigang

2017-01-01

Circulating tumor cells (CTCs) have shown promising potential as liquid biopsies that facilitate early detection, prognosis, therapeutic target selection and monitoring treatment response. CTCs in most cancer patients are low in abundance and heterogeneous in morphological and phenotypic profiles, which complicate their enrichment and subsequent characterization. Several methodologies for CTC enrichment and characterization have been developed over the past few years. However, integrating recent advances in CTC biology into these methodologies and the selection of appropriate enrichment and characterization methods for specific applications are needed to improve the reliability of CTC biopsies. In this review, we summarize recent advances in the studies of CTC biology, including the mechanisms of their generation and their potential forms of existence in blood, as well as the current CTC enrichment technologies. We then critically examine the selection of methods for appropriately enriching CTCs for further investigation of their clinical applications. PMID:28819450

[Current teaching, learning and examination methods in medical education and potential applications in rehabilitative issues].

PubMed

Schwarzkopf, S R; Morfeld, M; Gülich, M; Lay, W; Horn, K; Mau, W

2007-04-01

With introduction of the new Federal Medical Licensing Regulations (Approbationsordnung) in Germany, integrated teaching in "Rehabilitation, Physical Medicine, Naturopathic Treatment" (Querschnittsbereich Q12) has become obligatory for the first time. Furthermore, the new Regulations require the medical faculties in Germany to realize an innovative didactic orientation in teaching. This paper provides an overview of recent applications of teaching techniques and examination methods in medical education with special consideration of the new integrated course Q12 and further teaching methods related to rehabilitative issues. Problem-oriented learning (POL), problem-based learning (PBL), bedside teaching, eLearning, and the examination methods Objective Structured Clinical Examination (OSCE) and Triple Jump are in the focus. This overview is intended as the basis for subsequent publications of the Commission for Undergraduate and Postgraduate Training of the German Society of Rehabilitation Science (DGRW), which will present examples of innovative teaching material.

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

PubMed Central

Traina, Tiffany A.; Dugan, Ute; Higgins, Brian; Kolinsky, Kenneth; Theodoulou, Maria; Hudis, Clifford A.; Norton, Larry

2011-01-01

Background To hasten and improve anticancer drug development, we created a novel approach to generating and analyzing preclinical dose-scheduling data so as to optimize benefit-to-toxicity ratios. Methods We applied mathematical methods based upon Norton-Simon growth kinetic modeling to tumor-volume data from breast cancer xenografts treated with capecitabine (Xeloda®, Roche) at the conventional schedule of 14 days of treatment followed by a 7-day rest (14 - 7). Results The model predicted that 7 days of treatment followed by a 7-day rest (7 - 7) would be superior. Subsequent preclinical studies demonstrated that this biweekly capecitabine schedule allowed for safe delivery of higher daily doses, improved tumor response, and prolonged animal survival. Conclusions We demonstrated that the application of Norton-Simon modeling to the design and analysis of preclinical data predicts an improved capecitabine dosing schedule in xenograft models. This method warrants further investigation and application in clinical drug development. PMID:20519801

hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine.

PubMed

Falgreen, Steffen; Ellern Bilgrau, Anders; Brøndum, Rasmus Froberg; Hjort Jakobsen, Lasse; Have, Jonas; Lindblad Nielsen, Kasper; El-Galaly, Tarec Christoffer; Bødker, Julie Støve; Schmitz, Alexander; H Young, Ken; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2016-01-01

Dozens of omics based cancer classification systems have been introduced with prognostic, diagnostic, and predictive capabilities. However, they often employ complex algorithms and are only applicable on whole cohorts of patients, making them difficult to apply in a personalized clinical setting. This prompted us to create hemaClass.org, an online web application providing an easy interface to one-by-one RMA normalization of microarrays and subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin and chemotherapeutic sensitivity classes. Classification results for one-by-one array pre-processing with and without a laboratory specific RMA reference dataset were compared to cohort based classifiers in 4 publicly available datasets. Classifications showed high agreement between one-by-one and whole cohort pre-processsed data when a laboratory specific reference set was supplied. The website is essentially the R-package hemaClass accompanied by a Shiny web application. The well-documented package can be used to run the website locally or to use the developed methods programmatically. The website and R-package is relevant for biological and clinical lymphoma researchers using affymetrix U-133 Plus 2 arrays, as it provides reliable and swift methods for calculation of disease subclasses. The proposed one-by-one pre-processing method is relevant for all researchers using microarrays.

Pathologically Diagnosed Placenta Accreta and Hemorrhagic Morbidity in a Subsequent Pregnancy.

PubMed

Roeca, Cassandra; Little, Sarah E; Carusi, Daniela A

2017-02-01

To identify the relationship between pathologically diagnosed placenta accreta and risk of major morbidity in a subsequent pregnancy. We conducted a retrospective cohort study of patients with pathologically diagnosed placenta accreta in an index pregnancy who returned with a subsequent pregnancy at our academic center from 2007 to 2015. Subsequent delivery outcomes included minor, major, or no morbidity. Minor morbidity included estimated blood loss 500-1,500 cc for vaginal and 1,000-1,500 cc for cesarean delivery, transfusion of one to three units of red cells, and minor surgical procedures. Major morbidity included estimated blood loss greater than 1,500 cc, transfusion of greater than three units of red cells, uterine artery embolization, unplanned laparotomy, or hysterectomy. Three hundred thirty-nine patients with pathologically diagnosed accreta did not undergo hysterectomy, and 39 (11.5%) of these returned for subsequent delivery. Of these, 14 (36%) had accretas that had been identified clinically in the index pregnancy. Twenty-one (54%) experienced morbidity in the index pregnancy, 16 of these (76%) minor and five (24%) major. Of patients without morbidity in the first pregnancy, none experienced major morbidity in a subsequent pregnancy, whereas 6 of 21 (29%) with any index morbidity had a subsequent major morbid outcome (P=.02). Of those with a morbid index delivery, 25% had either a clinical or pathologic accreta diagnosis at follow-up compared with none of those who index accreta was nonmorbid (P=.05). Risk for major hemorrhagic morbidity after a prior pathologically diagnosed accreta depends on the clinical context. Preparation for major blood loss is indicated after any prior pregnancy complicated by hemorrhage or treatment of retained placenta with a pathologic accreta.

Frugal Chemoprevention: Targeting Nrf2 with Foods Rich in Sulforaphane

PubMed Central

Yang, Li; Palliyaguru, Dushani L.; Kensler, Thomas W.

2015-01-01

With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder carcinogenesis, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, pre-clinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2- Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention. PMID:26970133

Is speckle tracking actually helpful for cardiac resynchronization therapy?

PubMed

Tanaka, Hidekazu; Hirata, Ken-Ichi

2016-06-01

What is the specific role of echocardiography in cardiac resynchronization therapy (CRT)? CRT has proven to be highly effective for improving symptoms and survival of patients with advanced heart failure (HF) and wide QRS. However, a significant minority of patients do not respond favorably to CRT on the basis of standard clinical selection criteria, including the electrocardiographic QRS width. Subsequently, echocardiographic assessment of left ventricular (LV) dyssynchrony has been considered useful for CRT for selected responders, but findings by multicenter studies suggest that its predictive value was not sufficiently robust to replace routine selection criteria for CRT. A more recent approach, however, using speckle-tracking echocardiography yields more accurate quantification of regional wall contraction. Speckle-tracking approaches have therefore generated a great deal of interest about their clinical applications for CRT. Although reports on speckle tracking have not been included in any recommendations as to whether patients should undergo CRT based on the current guidelines, speckle tracking can play an important supplementary part in CRT on the basis of a case-by-case clinical decision for challenging cases. Here, we review the strengths of speckle-tracking methods, and their current potential for clinical use in CRT.

Improving public health by improving clinical trial guidelines and their application

PubMed Central

Landray, Martin J.; Bax, Jeroen J.; Alliot, Laurence; Buyse, Marc; Cohen, Adam; Collins, Rory; Hindricks, Gerhard; James, Stefan K.; Lane, Sile; Maggioni, Aldo P.; Meeker-O'Connell, Ann; Olsson, Gunnar; Pocock, Stuart J.; Rawlins, Michael; Sellors, Jonathan; Shinagawa, Kaori; Sipido, Karin R.; Smeeth, Liam; Stephens, Richard; Stewart, Murray W.; Stough, Wendy Gattis; Sweeney, Fergus; Van de Werf, Frans; Woods, Kerrie; Casadei, Barbara

2017-01-01

Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research. PMID:28329235

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

Participatory design methods for the development of a clinical telehealth service for neonatal homecare.

PubMed

Garne Holm, Kristina; Brødsgaard, Anne; Zachariassen, Gitte; Smith, Anthony C; Clemensen, Jane

2017-01-01

Neonatal homecare delivered during home visits by neonatal nurses is a common method for supporting families of preterm infants following discharge. Telehealth has been introduced for the provision of neonatal homecare, resulting in positive feedback from parents of preterm infants. While the benefits are beginning to be realised, widespread uptake of telehealth has been limited due to a range of logistical challenges. Understanding user requirements is important when planning and developing a clinical telehealth service. We therefore used participatory design to develop a clinical telehealth service for neonatal homecare. The study adopted a participatory design approach to engage users in the development and design of a new telehealth service. Participatory design embraces qualitative research methods. Creative and technical workshops were conducted as part of the study. Tests of the telehealth service were conducted in the neonatal unit. Participants in this study were former and current parents of preterm infants eligible for neonatal homecare, and clinical staff (medical and nursing) from the neonatal unit. Preterm infants accompanied their parents. Based on the results obtained during the workshops and subsequent testing, we developed an application (app), which was integrated into the medical record at the neonatal unit. The app was used to initiate videoconferences and chat messages between the family at home and the neonatal unit, and to share information regarding infant growth and well-being. Results obtained from the workshops and testing demonstrated the importance of involving users when developing new telehealth applications. The workshops helped identify the challenges associated with delivery of the service, and helped instruct the design of a new telehealth service for neonatal homecare based on the needs of parents and clinical staff.

Institutionalizing Telemedicine Applications: The Challenge of Legitimizing Decision-Making

PubMed Central

Lettieri, Emanuele

2011-01-01

During the last decades a variety of telemedicine applications have been trialed worldwide. However, telemedicine is still an example of major potential benefits that have not been fully attained. Health care regulators are still debating why institutionalizing telemedicine applications on a large scale has been so difficult and why health care professionals are often averse or indifferent to telemedicine applications, thus preventing them from becoming part of everyday clinical routines. We believe that the lack of consolidated procedures for supporting decision making by health care regulators is a major weakness. We aim to further the current debate on how to legitimize decision making about the institutionalization of telemedicine applications on a large scale. We discuss (1) three main requirements— rationality, fairness, and efficiency—that should underpin decision making so that the relevant stakeholders perceive them as being legitimate, and (2) the domains and criteria for comparing and assessing telemedicine applications—benefits and sustainability. According to these requirements and criteria, we illustrate a possible reference process for legitimate decision making about which telemedicine applications to implement on a large scale. This process adopts the health care regulators’ perspective and is made up of 2 subsequent stages, in which a preliminary proposal and then a full proposal are reviewed. PMID:21955510

Evaluation of a Clinical Pharmacist Intervention on Clinical and Drug-Related Problems Among Coronary Heart Disease Inpatients: A pre-experimental prospective study at a general hospital in Indonesia.

PubMed

Sagita, Vina A; Bahtiar, Anton; Andrajati, Retnosari

2018-02-01

This study aimed to evaluate the role of a clinical pharmacist intervention in decreasing subsequent clinical and drug-related problems (DRPs) among coronary heart disease (CHD) inpatients with at least one previous DRP. This pre-experimental study with a pre-post design was carried out from January to April 2017 among inpatients with at least one previous DRP at a general hospital in Tangerang District, Banten, Indonesia. Clinical and DRPs were documented prospectively by a clinical pharmacist, with DRPs classified using Version 6.2 of the DRP classification scheme of the Pharmaceutical Care Network Europe Foundation. The intervention consisted of a discussion of identified DRPs with physicians, patients, pharmaceutical logistics clerks, nurses and nutritionists. Following this, any subsequent clinical and DRPs were re-identified and further interventions were conducted as necessary. A total of 75 inpatients were included in the study. Pre-intervention, there were 443 DRPs and 202 clinical problems. The most frequent DRPs were adverse drug reactions (52.6%), followed by drug effects (41.8%). Most DRPs were of moderate severity and would have resulted in moderate consequences had the pharmacist not intervened. The interventions resulted in a significant reduction in the number of DRPs, type of DRPs and number of clinical problems ( P <0.05 each). Patients with complications were 26.047 times more likely to have no reduction or an increased number of clinical problems compared to patients without complications ( P <0.05). Clinical pharmacist interventions were found to reduce subsequent DRPs and clinical problems among CHD patients with at least one previous DRP.

Nursing students' intentions to use research as a predictor of use one year post graduation: a prospective study.

PubMed

Forsman, Henrietta; Wallin, Lars; Gustavsson, Petter; Rudman, Ann

2012-09-01

Graduating nursing students are expected to have acquired the necessary skills to provide research-based care to patients. However, recent studies have shown that new graduate nurses report their extent of research use as relatively low. Because behavior intention is a well-known predictor of subsequent behavior, this gives reasons to further investigate graduating nursing students' intentions to use research in clinical practice after undergraduate study. To investigate graduating nursing students' intentions to use research in clinical practice and, furthermore, to investigate whether intention in itself and as a mediating variable can predict subsequent research use behavior in clinical practice one year post graduation. A follow-up study was performed of graduating nursing students in their final semester of undergraduate study (2006) and at one year post graduation (2008). Data were collected within the larger national survey LANE (Longitudinal Analysis of Nursing Education). A sample of 1319 respondents was prospectively followed. Graduating nursing students' intentions to use research instrumentally were studied as a predictor of their subsequent instrumental research use one year post graduation. A statistical full mediation model was tested to evaluate the effects of intention and factors from undergraduate study on subsequent research use in daily care. Thirty-four percent of the nursing students intended to use research on more than half or almost every working shift in their future clinical practice. Intention showed a direct effect on research use behavior. In addition, significant indirect effects on research use were shown for capability beliefs (regarding practicing the principles of evidence-based practice) and perceived support for research use (from campus and clinical education), where intention acted as a mediating factor for those effects. Students rated a modest level of intention to use research evidence. Intentions close to graduation acted as an essential predictor of subsequent research use behavior, both through a direct effect and as a mediating variable. These findings give support for designing future interventions aiming at influencing students' intention to use research to improve subsequent behavior. Focusing on strengthening students' capability beliefs and providing support for research use appear as promising target activities. Copyright © 2012 Elsevier Ltd. All rights reserved.

The C-reactive protein.

PubMed

Clyne, B; Olshaker, J S

1999-01-01

C-reactive protein (CRP) was identified in 1930 and was subsequently considered to be an "acute phase protein," an early indicator of infectious or inflammatory conditions. Since its discovery, CRP has been studied as a screening device for inflammation, a marker for disease activity, and as a diagnostic adjunct. Improved methods of quantifying CRP have led to increased application to clinical medicine. In the emergency department (ED), CRP must be interpreted in the clinical context; no single value can be used to rule in or rule out a specific diagnosis. We conclude that CRP has limited utility in the ED. It may be a useful adjunct to serial examinations in equivocal presentations of appendicitis in those centers without ready access to computed tomography (CT) scan. It may be elevated with complications or treatment failures in patients with pneumonia, pancreatitis, pelvic inflammatory disease (PID), and urinary tract infections. In patients with meningitis, neonatal sepsis, and occult bacteremia, CRP is usually elevated. However, CRP has no role in diagnosing these clinical entities, and a normal CRP level should never delay antibiotic coverage.

Nanoparticles for Cardiovascular Imaging and Therapeutic Delivery, Part 1: Compositions and Features.

PubMed

Stendahl, John C; Sinusas, Albert J

2015-10-01

Imaging agents made from nanoparticles are functionally versatile and have unique properties that may translate to clinical utility in several key cardiovascular imaging niches. Nanoparticles exhibit size-based circulation, biodistribution, and elimination properties different from those of small molecules and microparticles. In addition, nanoparticles provide versatile platforms that can be engineered to create both multimodal and multifunctional imaging agents with tunable properties. With these features, nanoparticulate imaging agents can facilitate fusion of high-sensitivity and high-resolution imaging modalities and selectively bind tissues for targeted molecular imaging and therapeutic delivery. Despite their intriguing attributes, nanoparticulate imaging agents have thus far achieved only limited clinical use. The reasons for this restricted advancement include an evolving scope of applications, the simplicity and effectiveness of existing small-molecule agents, pharmacokinetic limitations, safety concerns, and a complex regulatory environment. This review describes general features of nanoparticulate imaging agents and therapeutics and discusses challenges associated with clinical translation. A second, related review to appear in a subsequent issue of JNM highlights nuclear-based nanoparticulate probes in preclinical cardiovascular imaging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection.

PubMed

Portugal, Silvia; Tran, Tuan M; Ongoiba, Aissata; Bathily, Aboudramane; Li, Shanping; Doumbo, Safiatou; Skinner, Jeff; Doumtabe, Didier; Kone, Younoussou; Sangala, Jules; Jain, Aarti; Davies, D Huw; Hung, Christopher; Liang, Li; Ricklefs, Stacy; Homann, Manijeh Vafa; Felgner, Philip L; Porcella, Stephen F; Färnert, Anna; Doumbo, Ogobara K; Kayentao, Kassoum; Greenwood, Brian M; Traore, Boubacar; Crompton, Peter D

2017-03-01

Chronic asymptomatic Plasmodium falciparum infections are common in endemic areas and are thought to contribute to the maintenance of malaria immunity. Whether treatment of these infections increases the subsequent risk of clinical episodes of malaria is unclear. In a 3-year study in Mali, asymptomatic individuals with or without P. falciparum infection at the end of the 6-month dry season were identified by polymerase chain reaction (PCR), and clinical malaria risk was compared during the ensuing 6-month malaria transmission season. At the end of the second dry season, 3 groups of asymptomatic children were identified: (1) children infected with P. falciparum as detected by rapid diagnostic testing (RDT) who were treated with antimalarials (n = 104), (2) RDT-negative children whose untreated P. falciparum infections were detected retrospectively by PCR (n = 55), and (3) uninfected children (RDT/PCR negative) (n = 434). Clinical malaria risk during 2 subsequent malaria seasons was compared. Plasmodium falciparum-specific antibody kinetics during the dry season were compared in children who did or did not harbor asymptomatic P. falciparum infections. Chronic asymptomatic P. falciparum infection predicted decreased clinical malaria risk during the subsequent malaria season(s); treatment of these infections did not alter this reduced risk. Plasmodium falciparum-specific antibodies declined similarly in children who did or did not harbor chronic asymptomatic P. falciparum infection during the dry season. These findings challenge the notion that chronic asymptomatic P. falciparum infection maintains malaria immunity and suggest that mass drug administration during the dry season should not increase the subsequent risk of clinical malaria. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies.

PubMed

Barata, Pedro C; Gopalakrishnan, Dhrmesh; Koshkin, Vadim S; Mendiratta, Prateek; Karafa, Matt; Allman, Kimberly; Martin, Allison; Beach, Jennifer; Profusek, Pam; Tyler, Allison; Wood, Laura; Ornstein, Moshe; Gilligan, Timothy; Rini, Brian I; Garcia, Jorge A; Grivas, Petros

2018-04-06

Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials. The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials. This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017. Seventy-nine patients, median age 72 years (range 29-93), 71% men and 76% ECOG PS 0-1, were identified. Most patients (79%) had primary cancer in the bladder, 62% had prior surgery, and 75% received at least one prior line of treatment (34 patients had prior cisplatin-based chemotherapy). Best response included 18% partial response, 29% stable disease, and 53% progressive disease. Patients were on atezolizumab for a median of 2.7 months (95%CI, 1.8-3.6) and median PFS was 3.2 months (95%CI, 1.6-4.8). A total of 33 (42%) patients had significant (any cause) AEs, including grade 4 hyperbilirubinemia in two patients; no toxic deaths were reported. At time of data analysis, only 18% of patients received at least one subsequent line of treatment for a median of 1.8 months (95%CI, 0.0-5.0) while 42% were referred to palliative care/hospice or died. Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.

NK-92: an 'off-the-shelf therapeutic' for adoptive natural killer cell-based cancer immunotherapy.

PubMed

Suck, Garnet; Odendahl, Marcus; Nowakowska, Paulina; Seidl, Christian; Wels, Winfried S; Klingemann, Hans G; Tonn, Torsten

2016-04-01

Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however always remain variable due to individual differences of donors or patients. Long-term storage of clinical NK cell lots to allow repeated clinical applications remains an additional challenge. In contrast, the established and well-characterized cell line NK-92 can be easily and reproducibly expanded from a good manufacturing practice (GMP)-compliant cryopreserved master cell bank. Moreover, no cost-intensive cell purification methods are required. To date, NK-92 has been intensively studied. The cells displayed superior cytotoxicity against a number of tumor types tested, which was confirmed in preclinical mouse studies. Subsequent clinical testing demonstrated safety of NK-92 infusions even at high doses. Despite the phase I nature of the trials conducted so far, some efficacy was noted, particularly against lung tumors. Furthermore, to overcome tumor resistance and for specific targeting, NK-92 has been engineered to express a number of different chimeric antigen receptors (CARs), including targeting, for example, CD19 or CD20 (anti-B cell malignancies), CD38 (anti-myeloma) or human epidermal growth factor receptor 2 (HER2; ErbB2; anti-epithelial cancers). The concept of an NK cell line as an allogeneic cell therapeutic produced 'off-the-shelf' on demand holds great promise for the development of effective treatments.

Influence of Rapeseed Cake on Heavy Metal Uptake by a Subsequent Rice Crop After Phytoextraction Using Sedum plumbizincicola.

PubMed

Zhou, Liqiang; Wu, Longhua; Li, Zhu; Yang, Bingfan; Yin, Bin; Luo, Yongming; Christie, Peter

2015-01-01

A glasshouse pot experiment was conducted to study the effects of phytoextraction by Sedum plumbizincicola and application of rapeseed cake (RSC) on heavy metal accumulation by a subsequent rice (Oryza sativa L.) crop in a contaminated paddy soil collected from east China. After phytoextraction by S. plumbizincicola the soil and brown rice Cd concentrations effectively declined. After phytoextraction, RSC application reduced brown rice Cd concentrations in the subsequent rice crop to 0.23-0.28 mg kg(-1), almost down to the standard limit (0.2 mg kg(-1)). After phytoextraction and then application of RSC, the soil solution pH, dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) concentrations increased during early stages of rice growth resulting directly and indirectly in lowering the bioavailability of the heavy metals. Thus the grain yield of the subsequent rice crop increased and the heavy metals in the brown rice declined significantly. In this contaminated acid soil, growing the hyperaccumulator S. plumbizincicola and rice in rotation together with RSC application may therefore be regarded as a viable strategy for safe grain production and bioremediation.

Developing a knowledge base to support the annotation of ultrasound images of ectopic pregnancy.

PubMed

Dhombres, Ferdinand; Maurice, Paul; Friszer, Stéphanie; Guilbaud, Lucie; Lelong, Nathalie; Khoshnood, Babak; Charlet, Jean; Perrot, Nicolas; Jauniaux, Eric; Jurkovic, Davor; Jouannic, Jean-Marie

2017-01-31

Ectopic pregnancy is a frequent early complication of pregnancy associated with significant rates of morbidly and mortality. The positive diagnosis of this condition is established through transvaginal ultrasound scanning. The timing of diagnosis depends on the operator expertise in identifying the signs of ectopic pregnancy, which varies dramatically among medical staff with heterogeneous training. Developing decision support systems in this context is expected to improve the identification of these signs and subsequently improve the quality of care. In this article, we present a new knowledge base for ectopic pregnancy, and we demonstrate its use on the annotation of clinical images. The knowledge base is supported by an application ontology, which provides the taxonomy, the vocabulary and definitions for 24 types and 81 signs of ectopic pregnancy, 484 anatomical structures and 32 technical elements for image acquisition. The knowledge base provides a sign-centric model of the domain, with the relations of signs to ectopic pregnancy types, anatomical structures and the technical elements. The evaluation of the ontology and knowledge base demonstrated a positive feedback from a panel of 17 medical users. Leveraging these semantic resources, we developed an application for the annotation of ultrasound images. Using this application, 6 operators achieved a precision of 0.83 for the identification of signs in 208 ultrasound images corresponding to 35 clinical cases of ectopic pregnancy. We developed a new ectopic pregnancy knowledge base for the annotation of ultrasound images. The use of this knowledge base for the annotation of ultrasound images of ectopic pregnancy showed promising results from the perspective of clinical decision support system development. Other gynecological disorders and fetal anomalies may benefit from our approach.

SERA -- An advanced treatment planning system for neutron therapy and BNCT

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

Nigg, D.W.; Wemple, C.A.; Wessol, D.E.

1999-09-01

Detailed treatment planning calculations on a patient-specific basis are required for boron neutron capture therapy (BNCT). Two integrated treatment planning systems developed specifically for BNCT have been in clinical use in the United States over the past few years. The MacNCTPLAN BNCT treatment planning system is used in the clinical BNCT trials that are underway at the Massachusetts Institute of Technology. A second system, BNCT{_}rtpe (BNCT radiation therapy planning environment), developed independently by the Idaho national Engineering and Environmental Laboratory (INEEL) in collaboration with Montana State University (MSU), is used for treatment planning in the current series of BNCT clinicalmore » trials for glioblastoma at Brookhaven National Laboratory (BNL). This latter system is also licensed for use at several other BNCT research facilities worldwide. Although the currently available BNCT planning systems have served their purpose well, they suffer from somewhat long computation times (2 to 3 CPU-hours or more per field) relative to standard photon therapy planning software. This is largely due to the need for explicit three-dimensional solutions to the relevant transport equations. The simplifying approximations that work well for photon transport computations are not generally applicable to neutron transport computations. Greater computational speeds for BNCT treatment planning must therefore generally be achieved through the application of improved numerical techniques rather than by simplification of the governing equations. Recent efforts at INEEL and MSU have been directed toward this goal. This has resulted in a new paradigm for this type of calculation and the subsequent creation of the new simulation environment for radiotherapy applications (SERA) treatment planning system for BNCT. SERA is currently in initial clinical testing in connection with the trials at BNL, and it is expected to replace the present BNCT{_}rtpe system upon general release during 1999.« less

Nanoparticle Enhancement Cascade for Sensitive Multiplex Measurements of Biomarkers in Complex Fluids with Surface Plasmon Resonance Imaging.

PubMed

Hendriks, Jan; Stojanovic, Ivan; Schasfoort, Richard B M; Saris, Daniël B F; Karperien, Marcel

2018-06-05

There is a large unmet need for reliable biomarker measurement systems for clinical application. Such systems should meet challenging requirements for large scale use, including a large dynamic detection range, multiplexing capacity, and both high specificity and sensitivity. More importantly, these requirements need to apply to complex biological samples, which require extensive quality control. In this paper, we present the development of an enhancement detection cascade for surface plasmon resonance imaging (SPRi). The cascade applies an antibody sandwich assay, followed by neutravidin and a gold nanoparticle enhancement for quantitative biomarker measurements in small volumes of complex fluids. We present a feasibility study both in simple buffers and in spiked equine synovial fluid with four cytokines, IL-1β, IL-6, IFN-γ, and TNF-α. Our enhancement cascade leads to an antibody dependent improvement in sensitivity up to 40 000 times, resulting in a limit of detection as low as 50 fg/mL and a dynamic detection range of more than 7 logs. Additionally, measurements at these low concentrations are highly reliable with intra- and interassay CVs between 2% and 20%. We subsequently showed this assay is suitable for multiplex measurements with good specificity and limited cross-reactivity. Moreover, we demonstrated robust detection of IL-6 and IL-1β in spiked undiluted equine synovial fluid with small variation compared to buffer controls. In addition, the availability of real time measurements provides extensive quality control opportunities, essential for clinical applications. Therefore, we consider this method is suitable for broad application in SPRi for multiplex biomarker detection in both research and clinical settings.

Design and Development of a New Multi-Projection X-Ray System for Chest Imaging

NASA Astrophysics Data System (ADS)

Chawla, Amarpreet S.; Boyce, Sarah; Washington, Lacey; McAdams, H. Page; Samei, Ehsan

2009-02-01

Overlapping anatomical structures may confound the detection of abnormal pathology, including lung nodules, in conventional single-projection chest radiography. To minimize this fundamental limiting factor, a dedicated digital multi-projection system for chest imaging was recently developed at the Radiology Department of Duke University. We are reporting the design of the multi-projection imaging system and its initial performance in an ongoing clinical trial. The system is capable of acquiring multiple full-field projections of the same patient along both the horizontal and vertical axes at variable speeds and acquisition frame rates. These images acquired in rapid succession from slightly different angles about the posterior-anterior (PA) orientation can be correlated to minimize the influence of overlying anatomy. The developed system has been tested for repeatability and motion blur artifacts to investigate its robustness for clinical trials. Excellent geometrical consistency was found in the tube motion, with positional errors for clinical settings within 1%. The effect of tube-motion on the image quality measured in terms of impact on the modulation transfer function (MTF) was found to be minimal. The system was deemed clinic-ready and a clinical trial was subsequently launched. The flexibility of image acquisition built into the system provides a unique opportunity to easily modify it for different clinical applications, including tomosynthesis, correlation imaging (CI), and stereoscopic imaging.

Strategies for Isolation and Molecular Profiling of Circulating Tumor Cells.

PubMed

Chen, Jia-Yang; Chang, Ying-Chih

2017-01-01

Cancer is the leading cause of death by disease worldwide, and metastasis is responsible for more than 90% of the mortality of cancer patients. Metastasis occurs when tumor cells leave the primary tumor, travel through the blood stream as circulating tumor cells (CTCs), and then colonize secondary tumors at sites distant from the primary tumor. The capture, identification, and analysis of CTCs offer both scientific and clinical benefits. On the scientific side, the analysis of CTCs could help elucidate possible genetic alterations and signaling pathway aberrations during cancer progression, which could then be used to find new methods to stop cancer progression. On the clinical side, non-invasive testing of a patient's blood for CTCs can be used for patient diagnosis and prognosis, as well as subsequent monitoring of treatment efficacy in routine clinical practice. Additionally, investigation of CTCs early in the progression of cancer may reveal targets for initial cancer detection and for anti-cancer treatment. This chapter will evaluate strategies and devices used for the isolation and identification of CTCs directly from clinical samples of blood. Recent progress in the understanding of the significance of both single CTCs and circulating tumor microemboli will be discussed. Also, advancements in the use of CTC-based liquid biopsy in clinical diagnosis and the potential of CTC-based molecular characterization for use in clinical applications will be summarized.

Preliminary application of hybrid operation in the treatment of carotid artery stenosis in patients with complex ischemic cerebrovascular diseases

PubMed Central

Zhang, Liyong; Xing, Tao; Geng, Fenyang; Du, Lixin; Wang, Jiyue

2014-01-01

Along with the recent development of intraluminal interventional techniques and correlated imaging methods, one-stop hybrid operation has become a new focus in clinical settings. The aim of this study is to discuss the clinical significance of the one-stop hybrid endarterectomy surgery in the treatment of complex ischemic cerebrovascular diseases. In this study, clinical data from 10 patients with complex ischemic cerebrovascular diseases (including multi-vessel severe stenosis of the internal extracranial carotid artery, single vessel series stenosis of the internal extracranial carotid artery, in-stent restenosis, complete occlusion of the common carotid or the internal carotid artery) admitted to Beijing Xuanwu Hospital and Liaocheng Brain Hospital, were retrospectively analyzed. All enrolled subjects underwent three types of hybrid operations. The clinical efficacy of this surgery was subsequently assessed in this clinical trial. The results indicated that no related surgical complications were noted during the perioperative period. Intraoperative and postoperative imaging revealed no signs of vascular stenosis, the blood supply recovered, and clinical symptoms were alleviated. The follow-up lasted for 6 to 12 months. Imaging re-examination showed no evidence of re-stenosis and good blood circulation was present in the recanalized blood vessels. Favorable treatment efficacy was achieved. The intracranial blood supply was significantly improved postoperatively. In conclusion, one-stop hybrid operation plays an important role in treating complex stenosis cerebrovascular diseases. PMID:25197423

Intralesional Infiltration with Meglumine Antimoniate for the Treatment of Leishmaniasis Recidiva Cutis in Ecuador.

PubMed

Calvopiña, Manuel; Cevallos, William; Paredes, Yolanda; Puebla, Edison; Flores, Jessica; Loor, Richard; Padilla, José

2017-11-01

Meglumine Antimoniate (MA), administered intramuscularly for 21 continuous days is the recommended treatment of leishmaniases in Ecuador. However, because of its toxicity and requirement for intramuscular injections, treatment is frequently abandoned before completion. In addition, therapeutic failure and reactivation are not uncommon. Here we evaluate the efficacy and safety of MA administered intralesionally (IL) in leishmaniasis recidiva cutis (LRC). LRC is a special clinical variant of cutaneous leishmaniasis, characterized by reactivation at the edges of a primary cured lesion, presenting with active papules around the scar. Twenty-one patients were included in the study. All were diagnosed parasitologically by one of three diagnostic methods (smear, culture, and Leishmanin skin test). Each patient received MA intralesionally weekly for 4 weeks. Each papule was infiltrated until complete saturation. On average, patients received 1 mL of MA per administration. The criterion of cure was the complete resolution of the papules. Follow up was performed at 30, 90, and 180 days after treatment. At day 30 after treatment, 19 (90.5%) of 21 patients were clinically cured. The two patients, who did not heal by the fourth application, were cured on the seventh and eighth dose, achieving a clinical cure of 100% without subsequent reactivation. Mild to moderate local pain during infiltration was the only adverse reaction experienced by 81% of patients. In one case, subsequent infiltrations were discontinued because of a local allergic reaction. Complete compliance of patients to treatment and the small volume of drug administered make this method of administering MA an effective, safe, and inexpensive alternative. Consequently, IL could replace intramuscular administration in the treatment of LRC in Ecuador.

Clinical Diagnosis of Dental Caries in the 21st Century: Introductory Paper - ORCA Saturday Afternoon Symposium, 2016.

PubMed

Machiulskiene, Vita; Carvalho, Joana Christina

2018-03-05

Classifications employed to measure dental caries should first of all reflect the dynamics of the disease, in order to provide a solid basis for subsequent treatment decisions and for further monitoring of dental health of individual patients and populations. The contemporary philosophy of dental caries management implies that nonoperative treatment of caries lesions should be implemented whenever possible, limiting operative interventions to the severe and irreversible cases. The ORCA Saturday Afternoon Symposium 2016, held back-to-back to the 63rd ORCA Congress in Athens, Greece, was intended to provide an update on general requirements for clinical caries diagnosis and to overview caries diagnostic classifications including their rationale, validation, advantages, and limitations. Clinical caries diagnostic criteria and caries management outcomes are interrelated, and any diagnostic classification disregarding this concept is outdated, according to the current understanding of oral health care. Choosing clinical caries diagnostic classifications that assess the activity status of detected lesions should be a priority for dental professionals since these classifications favor the best clinical practice directed towards nonoperative interventions. The choice of clinical caries diagnostic classifications in research, in clinical practice, and in public health services should be guided by the best available scientific evidence. The clinical caries diagnostic classifications should be universally applicable in all these fields. Policy making in oral health care and the underlying policy analyses should follow the same standards. Any clinical caries diagnostic classification disregarding the universality of its use is of limited or no interest in the context of the clinical caries diagnosis of today. © 2018 S. Karger AG, Basel.

Clinical application of real-time PCR to screening critically ill and emergency-care surgical patients for methicillin-resistant Staphylococcus aureus: a quantitative analytical study.

PubMed

Herdman, M Trent; Wyncoll, Duncan; Halligan, Eugene; Cliff, Penelope R; French, Gary; Edgeworth, Jonathan D

2009-12-01

The clinical utility of real-time PCR screening assays for methicillin (methicillin)-resistant Staphylococcus aureus (MRSA) colonization is constrained by the predictive values of their results: as MRSA prevalence falls, the assay's positive predictive value (PPV) drops, and a rising proportion of positive PCR assays will not be confirmed by culture. We provide a quantitative analysis of universal PCR screening of critical care and emergency surgical patients using the BD GeneOhm MRSA PCR system, involving 3,294 assays over six months. A total of 248 PCR assays (7.7%) were positive; however, 88 failed to be confirmed by culture, giving a PPV of 65%. Multivariate analysis was performed to compare PCR-positive culture-positive (P+C+) and PCR-positive culture-negative (P+C-) assays. P+C- results were positively associated with a history of methicillin-sensitive Staphylococcus aureus infection or colonization (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.32 to 7.54) and high PCR thresholds of signal intensity, indicative of a low concentration of target DNA (OR, 1.19 per cycle; 95% CI, 1.11 to 1.26). P+C- results were negatively associated with a history of MRSA infection or colonization (OR, 0.19; 95% CI, 0.09 to 0.42) and male sex (OR, 0.40; 95% CI, 0.20 to 0.81). P+C+ patients were significantly more likely to have subsequent positive MRSA culture assays and microbiological evidence of clinical MRSA infection. The risk of subsequent MRSA infection in P+C- patients was not significantly different from that in case-matched PCR-negative controls. We conclude that, given the low PPV and poor correlation between a PCR-positive assay and the clinical outcome, it would be prudent to await culture confirmation before altering infection control measures on the basis of a positive PCR result.

Mindfulness Meditation in Clinical Practice

ERIC Educational Resources Information Center

Salmon, Paul; Sephton, Sandra; Weissbecker, Inka; Hoover, Katherine; Ulmer, Christi; Studts, Jamie L.

2004-01-01

The practice of mindfulness is increasingly being integrated into contemporary clinical psychology. Based in Buddhist philosophy and subsequently integrated into Western health care in the contexts of psychotherapy and stress management, mindfulness meditation is evolving as a systematic clinical intervention. This article describes…

Femoral artery blood flow and microcirculatory perfusion during acute, low-level functional electrical stimulation in spinal cord injury.

PubMed

Barton, Thomas J; Low, David A; Janssen, Thomas W J; Sloots, Maurits; Smit, Christof A J; Thijssen, Dick H J

2018-04-19

Functional electrical stimulation (FES) may help to reduce the risk of developing macro- and microvascular complications in people with SCI. Low-intensity FES has significant clinical potential since this can be applied continuously throughout the day. This study examines the acute effects of low intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with SCI. Cross-sectional observation study METHODS: Eight participants with a motor complete SCI received 4x3 minutes of unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Femoral artery blood flow increased by 18.1% with the application of FES (P=0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P=0.004). Skin perfusion did not change during an individual block of stimulation (P=0.66). Skin perfusion progressively increased with each subsequent bout (P<0.001). There was no change in femoral or skin perfusion across time in the non-stimulated leg (all P>0.05). Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications.

Clinical application of laser treatment for cardiovascular surgery

PubMed Central

Okada, Masayoshi; Yoshida, Masato; Tsuji, Yoshihiko; Horii, Hiroyuki

2011-01-01

Background: Recently, several kinds of lasers have been widely employed in the field of medicine and surgery. However, laser applications are very rare in the field of cardiovascular surgery throughout the world. So, we have experimentally tried to use lasers in the field of cardiovascular surgery. There were three categories: 1) Transmyocardial laser revascularization (TMLR), 2) Laser vascular anastomosis, and 3) Laser angioplasty in the peripheral arterial diseases. By the way, surgery for ischemic heart disease has been widely performed in Japan. Especially coronary artery bypass grafting (CABG) for these patients has been done as a popular surgical method. Among these patients there are a few cases for whom CABG and percutaneous coronary intervention (PCI) could not be carried out, because of diffuse stenosis and small caliber of coronary arteries. Materials and methods of TMLR: A new method of tranasmyocardial revascularization by CO2 laser (output 100 W, irradiation time 0.2 sec) was experimentally performed to save severely ill patients. In this study, a feasibility of transmyocardial laser revascularization from left ventricular cavity through artificially created channels by laser was precisely evaluated. Results: In trials on dogs laser holes 0.2mm in diameter have been shown microscopically to be patent even 3 years after their creation, thus this procedure could be used as a new method of transmyocardial laser revascularization. Clinical application of TMLR: Subsequently, transmyocardial laser revascularization was employed in a 55-year-old male patient with severe angina pectoris who had undergone pericardiectomy 7 years before. He was completely recovered from severe chest pain. Conclusions of TMLR: This patient was the first successful case in the world with TMLR alone. This method might be done for the patients who percutaneous coronary intervention and coronary artery bypass grafting could be carried out. Laser vascular anastomosis: At present time, in vascular surgery there are some problems to keep long-term patency after anastomosis of the conventional suture method, especially for small-caliber vessels. Materials and methods of Laser vascular anastomosis: From these standpoints, a low energy CO2 laser was employed experimentally in vascular anastomosis for small-caliber vessels. Resullts of Laser vascular anastomosis: From preliminary experiments it could be concluded that the optimal laser output was 20–40 mW and irradiation time was 6–12 sec/mm for vascular anastomosis of small-caliber vessels in the extremities. And then, histologic findings and intensity of the laser anastomotic sites were investigated thereafter. Subseqently, good enough intensity and good healing of laser anastomotic sites as well as the conventional suture method could be observed. There were no statistic differences between laser and suture methods. A feasibility of laser anastomosis could be considered and clinical application could be recognized. Clinical applications of Laser vascular anastomosis: On February 21, 1985, arterio-venous laser anastomosis for the patient with renal failure was smoothly done and she could accept hemodialysis. Conclusions of Laser vascular anastomosis: This patient was the first clinical successful case in the world. Thereafter, Laser vascular anastomosis were in 111 patients with intermittent claudication, refractory crural ulcer, and coronary disorders. Thereafter, they are going well. Laser angioplasty: Laser angioplasty for peripheral arterial diseases. There are many methods to treat peripheral arterial diseases such as balloon method, atherectomy, laser technique and stenting graft in the field of endovascular treatment. Recent years, minimal invasive treatment should be employed even in the surgical treatment. However, there are different images between these methods. Materials and methods of Laser angioplasty: We have chosen to use laser for endovascular treatment for peripheral arterial diseases. We have tried to check between laser energy and vessel wall. Results of Laser angioplasty: Subsequently, it could be concluded that optimal conditions for laser angioplasty were 6 W in output and irradiation time was 5 sec. And with another method of feedback control system, temperature of metal tip probe was 200°C and irradiation time was 5 sec for each shot. And histological study and feasibility of angioscopic guidance could be done and clinical application was started. Until now, 115 patients were successfully treated with their life longevity. Conclusions of Laser angioplasty: Thus, laser applications were useful methods to treat a lot of patients with some ischemic problems. PMID:24155531

Reducing symptoms of major depressive disorder through a systematic training of general emotion regulation skills: protocol of a randomized controlled trial.

PubMed

Ehret, Anna M; Kowalsky, Judith; Rief, Winfried; Hiller, Wolfgang; Berking, Matthias

2014-01-27

Major Depressive Disorder is one of the most challenging mental health problems of our time. Although effective psychotherapeutic treatments are available, many patients fail to demonstrate clinically significant improvements. Difficulties in emotion regulation have been identified as putative risk and maintaining factors for Major Depressive Disorder. Systematically enhancing adaptive emotion regulation skills should thus help reduce depressive symptom severity. However, at this point, no study has systematically evaluated effects of increasing adaptive emotion regulation skills application on symptoms of Major Depressive Disorder. In the intended study, we aim to evaluate stand-alone effects of a group-based training explicitly and exclusively targeting general emotion regulation skills on depressive symptom severity and assess whether this training augments the outcome of subsequent individual cognitive behavioral therapy for depression. In the evaluation of the Affect Regulation Training, we will conduct a prospective randomized-controlled trial. Effects of the Affect Regulation Training on depressive symptom severity and outcomes of subsequent individual therapy for depression will be compared with an active, common factor based treatment and a waitlist control condition. The study sample will include 120 outpatients meeting criteria for Major Depressive Disorder. Depressive symptom severity as assessed by the Hamilton Rating Scale will serve as our primary study outcome. Secondary outcomes will include further indicators of mental health and changes in adaptive emotion regulation skills application. All outcomes will be assessed at intake and at 10 points in time over the course of the 15-month study period. Measures will include self-reports, observer ratings, momentary ecological assessments, and will be complemented in subsamples by experimental investigations and the analysis of hair steroids. If findings should support the hypothesis that enhancing regulation skills reduces symptom severity in Major Depressive Disorder, systematic emotion regulation skills training can enhance the efficacy and efficiency of current treatments for this severe and highly prevalent disorder. This study is registered with ClinicalTrials.gov, number NCT01330485.

Selective disulfide reduction for labeling and enhancement of Fab antibody fragments

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

Kirley, Terence L., E-mail: terry.kirley@uc.edu; Greis, Kenneth D.; Norman, Andrew B.

Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab’){sub 2} fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab’){sub 2} fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neithermore » homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. - Highlights: • TCEP agarose is effective for selective reduction of a single Fab disulfide bond. • This disulfide is solvent accessible and distant from the antigen binding site. • A variety of buffers of varying pHs can be used, simplifying subsequent steps. • The methods used are simple, easily verifiable, reproducible, and quantitative. • The selectively reduced Fab has many experimental and clinical applications.« less

Abortions: Does It Affect Subsequent Pregnancies?

MedlinePlus

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Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery.

PubMed

Mohammed, Leena; Ragab, Doaa; Gomaa, Hassan

2016-01-01

Engineered magnetic nanoparticles (MNPs) possess unique properties and hold great potential in biomedicine and clinical applications. With their magnetic properties and their ability to work at cellular and molecular level, MNP have been applied both in-vitro and in-vivo in targeted drug delivery and imaging. Focusing on Iron Oxide Superparamagnetic nanoparticles (SPIONs), this paper elaborates on the recent advances in development of hybrid polymeric-magnetic nanoparticles. Their main applications in drug delivery include Chemotherapeutics, Hyperthermia treatment, Radio-therapeutics, Gene delivary, and Biotheraputics. Physiochemical properties such as size, shape, surface and magnetic properties are key factors in determining their behavior. Additionally tailoring SPIONs surface is often vital for desired cell targetting and improved efficiency. Polymer coating is specifically reviewed with brief discussion of SPIONs administration routes. Commonly used drug release models for describing release mechanisms and the nanotoxicity aspects are also discussed. This review focus on superparamagnetic nanoparticles coated with different types of polymers starting with the key physiochemical features that dominate their behavior. The importance of surface modification is addressed. Subsequently, the major classes of polymer modified iron oxide nanoparticles is demonstrated according to their clinical use and application. Clinically approved nanoparticles are then addressed and the different routes of administration are mentioned. Lastly, mathematical models of drug release profile of the common used nanoparticles are addressed. MNPs emerging in recent medicine are remarkable for both imaging and therapeutics, particularly, as drug carriers for their great potential in targeted delivery and cancer treatment. Targeting ability and biocompatibility can be improved though surface coating which provides a mean to alter the surface features including physical characteristics and chemical functionality. The use of biocompatible polymers can prevent aggregation, increase colloidal stability, evades nanoparticles uptake by RES, and can provide a surface for conjugation of targeting ligands such as peptide and biomolecules with high affinity to target cells. Great efforts to bring MNPs from lab testing stage to clinic are needed to understand their physicochemical properties and how they behave in vivo, which resulted in few of them to exist in the market today. Although magnetic nanoparticles have not yet fully reached their optimal safety and efficiency due to the challenges they face in vivo, their shortcomings can be overcome through improvement of magnetictargeted carrier by pre-clinical trials and continuous studies.

Seal Technology in Gas Turbine Engines

DTIC Science & Technology

1978-08-01

ambient temperatures and 427*C (800*F). 3. Application as a part of the normal manufacturing sequence without subsequent finishing operations...of demonstrable hardnless with sharp, cutting edges. 4. The coating must be applied to a finish dimmsion without subsequent processing. 5. Application...The JC1-Iii 3.4 coating had a surface finish of 11 V metre (425 mioroinches). Both materials appeared to be adequately rough for the proposed

Bridging the Gap Between Scientists and Practitioners: The Challenge Before Us - Republished Article.

PubMed

Sobell, Linda Carter

2016-11-01

The need to develop effective and efficient strategies for the dissemination of evidence-based health care has been recognized by governments, researchers, and clinicians alike. However, recognition and implementation are separate issues. If scientists are to have a significant impact on clinical practice, they will have to learn a new way of "doing business." Lessons from the business community and from the field of diffusion of innovations research (dissemination research) have direct applicability to disseminating science-based clinical procedures. This paper presents two examples of the successful integration of science and clinical practice. The goal in each case was to address problems fundamental to dissemination research, specifically for addictions treatment. The first example demonstrates how scientists and practitioners successfully worked hand-in-hand to integrate science and practice, by creating a clinical protocol that subsequently served almost 300 clients. The second example describes the successful dissemination of a clinical research intervention into community settings. The key to effective dissemination was to make practitioners true partners in the research, development, and dissemination process. For the effective wedding of clinical science and practice on a wide scale, dissemination must be adopted as a value and become a major objective of health care organizations. Current health care emphasis on evidence-based practice suggests that alliances between practitioners and scientists will point the way to clinical standards of practice for the next millennium. Copyright © 2016. Published by Elsevier Ltd.

Validation of DWI pre-processing procedures for reliable differentiation between human brain gliomas.

PubMed

Vellmer, Sebastian; Tonoyan, Aram S; Suter, Dieter; Pronin, Igor N; Maximov, Ivan I

2018-02-01

Diffusion magnetic resonance imaging (dMRI) is a powerful tool in clinical applications, in particular, in oncology screening. dMRI demonstrated its benefit and efficiency in the localisation and detection of different types of human brain tumours. Clinical dMRI data suffer from multiple artefacts such as motion and eddy-current distortions, contamination by noise, outliers etc. In order to increase the image quality of the derived diffusion scalar metrics and the accuracy of the subsequent data analysis, various pre-processing approaches are actively developed and used. In the present work we assess the effect of different pre-processing procedures such as a noise correction, different smoothing algorithms and spatial interpolation of raw diffusion data, with respect to the accuracy of brain glioma differentiation. As a set of sensitive biomarkers of the glioma malignancy grades we chose the derived scalar metrics from diffusion and kurtosis tensor imaging as well as the neurite orientation dispersion and density imaging (NODDI) biophysical model. Our results show that the application of noise correction, anisotropic diffusion filtering, and cubic-order spline interpolation resulted in the highest sensitivity and specificity for glioma malignancy grading. Thus, these pre-processing steps are recommended for the statistical analysis in brain tumour studies. Copyright © 2017. Published by Elsevier GmbH.

Bioactivity of freeze-dried platelet-rich plasma in an adsorbed form on a biodegradable polymer material.

PubMed

Nakajima, Yu; Kawase, Tomoyuki; Kobayashi, Mito; Okuda, Kazuhiro; Wolff, Larry F; Yoshie, Hiromasa

2012-01-01

Owing to the necessity for the immediate preparation from patients' blood, autologous platelet-rich plasma (PRP) limits its clinical applicability. To address this concern and respond to emergency care and other unpredictable uses, we have developed a freeze-dried PRP in an adsorbed form on a biodegradable polymer material (Polyglactin 910). On the polymer filaments of PRP mesh, which was prepared by coating the polymer mesh with human fresh PRP and subsequent freeze-drying, platelets were incorporated, and related growth factors were preserved at high levels. This new PRP mesh preparation significantly and reproducibly stimulated the proliferation of human periodontal ligament cells in vitro and neovascularization in a chorioallantoic membrane assay. A full-thickness skin defect model in a diabetic mouse demonstrated the PRP mesh, although prepared from human blood, substantially facilitated angiogenesis, granulation tissue formation, and re-epithelialization without inducing severe inflammation in vivo. These data demonstrate that our new PRP mesh preparation functions as a bioactive material to facilitate tissue repair/regeneration. Therefore, we suggest that this bioactive material, composed of allogeneic PRP, could be clinically used as a promising alternative in emergency care or at times when autologous PRP is not prepared immediately before application.

Phase-transition thresholds and vaporization phenomena for ultrasound phase-change nanoemulsions assessed via high speed optical microscopy

PubMed Central

Sheeran, Paul S.; Matsunaga, Terry O.; Dayton, Paul A.

2015-01-01

Ultrasonically activated phase-change contrast agents (PCCAs) based on perfluorocarbon droplets have been proposed for a variety of therapeutic and diagnostic clinical applications. When generated at the nanoscale, droplets may be small enough to exit the vascular space and then be induced to vaporize with high spatial and temporal specificity by externally-applied ultrasound. The use of acoustical techniques for optimizing ultrasound parameters for given applications can be a significant challenge for nanoscale PCCAs due to the contributions of larger outlier droplets. Similarly, optical techniques can be a challenge due to the sub-micron size of nanodroplet agents and resolution limits of optical microscopy. In this study, an optical method for determining activation thresholds of nanoscale emulsions based on the in vitro distribution of bubbles resulting from vaporization of PCCAs after single, short (<10 cycles) ultrasound pulses is evaluated. Through ultra-high-speed microscopy it is shown that the bubbles produced early in the pulse from vaporized droplets are strongly affected by subsequent cycles of the vaporization pulse, and these effects increase with pulse length. Results show that decafluorobutane nanoemulsions with peak diameters on the order of 200 nm can be optimally vaporized with short pulses using pressures amenable to clinical diagnostic ultrasound machines. PMID:23760161

Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?

PubMed

Thompson, Andrew; Nelson, Barnaby; Bruxner, Annie; O'Connor, Karen; Mossaheb, Nilufar; Simmons, Magenta B; Yung, Alison

2013-04-01

Studies have attempted to identify additional risk factors within the group identified as 'ultra high risk' (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. A retrospective 'case-control' methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.

Do Patients Who Access Clinical Information on Patient Internet Portals Have More Primary Care Visits?

PubMed

Leveille, Suzanne G; Mejilla, Roanne; Ngo, Long; Fossa, Alan; Elmore, Joann G; Darer, Jonathan; Ralston, James D; Delbanco, Tom; Walker, Jan

2016-01-01

As health care costs alarm the nation and the debate increases about the impact of health information technologies, patients are reviewing their medical records increasingly through secure Internet portals. Important questions remain about the impact of portal use on office visits. To evaluate whether use of patient Internet portals to access records is associated with increased primary care utilization. A prospective cohort study. Primary care patients registered on patient Internet portals, within an integrated health system serving rural Pennsylvania and an academic medical center in Boston. Frequency of "clinical portal use" (days/2 mo intervals over 2 y) included secure messaging about clinical issues and viewing laboratory and radiology findings. In year 2, a subset of patients also gained access to their primary care doctor's visit notes. The main outcome was number of primary care office visits. In the first 2 months of the 2-year period, 14% of 44,951 primary care patients engaged in clinical portal use 2 or more days per month, 31% did so 1 day per month, and the remainder had no clinical portal use. Overall, adjusted for age, sex, and chronic conditions, clinical portal use was not associated with subsequent office visits. Fewer than 0.1% of patients engaged in high levels of clinical portal use (31 or more login days in 2 mo) that were associated with 1 or more additional visits in the subsequent 2 months (months 3 and 4). However, the reverse was true: office visits led to subsequent clinical portal use. Similar trends were observed among patients with or without access to visit notes. Patients turn to their portals following visits, but clinical portal use does not contribute to an increase in primary care visits.

Retail clinic visits and receipt of primary care.

PubMed

Reid, Rachel O; Ashwood, J Scott; Friedberg, Mark W; Weber, Ellerie S; Setodji, Claude M; Mehrotra, Ateev

2013-04-01

An increasing number of patients are visiting retail clinics for simple acute conditions. Physicians worry that visits to retail clinics will interfere with primary care relationships. No prior study has evaluated the impact of retail clinics on receipt of primary care. To assess the association between retail clinic use and receipt of key primary care functions. We performed a retrospective cohort analysis using commercial insurance claims from 2007 to 2009. We identified patients who had a visit for a simple acute condition in 2008, the "index visit". We divided these 127,358 patients into two cohorts according to the location of that index visit: primary care provider (PCP) versus retail clinic. We evaluated three functions of primary care: (1) where patients first sought care for subsequent simple acute conditions; (2) continuity of care using the Bice-Boxerman index; and (3) preventive care and diabetes management. Using a difference-in-differences approach, we compared care received in the 365 days following the index visit to care received in the 365 days prior, using propensity score weights to account for selection bias. Visiting a retail clinic instead of a PCP for the index visit was associated with a 27.7 visits per 100 patients differential reduction (p < 0 .001) in subsequent PCP visits for new simple acute conditions. Visiting a retail clinic instead of a PCP was also associated with decreased subsequent continuity of care (10.9 percentage-point differential reduction in Bice-Boxerman index, p < 0 .001). There was no differential change between the cohorts in receipt of preventive care or diabetes management. Retail clinics may disrupt two aspects of primary care: whether patients go to a PCP first for new conditions and continuity of care. However, they do not negatively impact preventive care or diabetes management.

A Pragmatic Approach to HIV-1 Drug Resistance Determination in Resource-Limited Settings by Use of a Novel Genotyping Assay Targeting the Reverse Transcriptase-Encoding Region Only

PubMed Central

Bronze, Michelle; Wallis, Carole L.; Stuyver, Lieven; Steegen, Kim; Balinda, Sheila; Kityo, Cissy; Stevens, Wendy; Rinke de Wit, Tobias F.; Schuurman, Rob

2013-01-01

In resource-limited settings (RLS), reverse transcriptase (RT) inhibitors form the backbone of first-line treatment regimens. We have developed a simplified HIV-1 drug resistance genotyping assay targeting the region of RT harboring all major RT inhibitor resistance mutation positions, thus providing all relevant susceptibility data for first-line failures, coupled with minimal cost and labor. The assay comprises a one-step RT-PCR amplification reaction, followed by sequencing using one forward and one reverse primer, generating double-stranded coverage of RT amino acids (aa) 41 to 238. The assay was optimized for all major HIV-1 group M subtypes in plasma and dried blood spot (DBS) samples using a panel of reference viruses for HIV-1 subtypes A to D, F to H, and circulating recombinant form 01_AE (CRF01_AE) and applied to 212 clinical plasma samples and 25 DBS samples from HIV-1-infected individuals from Africa and Europe. The assay was subsequently transferred to Uganda and applied locally on clinical plasma samples. All major HIV-1 subtypes could be detected with an analytical sensitivity of 5.00E+3 RNA copies/ml for plasma and DBS. Application of the assay on 212 clinical samples from African subjects comprising subtypes A to D, F to H (rare), CRF01_AE, and CRF02_AG at a viral load (VL) range of 6.71E+2 to 1.00E+7 (median, 1.48E+5) RNA copies/ml was 94.8% (n = 201) successful. Application on clinical samples in Uganda demonstrated a comparable success rate. Genotyping of clinical DBS samples, all subtype C with a VL range of 1.02E+3 to 4.49E+5 (median, 1.42E+4) RNA copies/ml, was 84.0% successful. The described assay greatly reduces hands-on time and the costs required for genotyping and is ideal for use in RLS, as demonstrated in a reference laboratory in Uganda and its successful application on DBS samples. PMID:23536405

Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

PubMed Central

Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.

2014-01-01

Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

The Mexican consensus on the treatment of hepatitis C.

PubMed

Aiza-Haddad, I; Ballesteros-Amozurrutia, A; Borjas-Almaguer, O D; Castillo-Barradas, M; Castro-Narro, G; Chávez-Tapia, N; Chirino-Sprung, R A; Cisneros-Garza, L; Dehesa-Violante, M; Flores-Calderón, J; Flores-Gaxiola, A; García-Juárez, I; González-Huezo, M S; González-Moreno, E I; Higuera-de la Tijera, F; Kershenobich-Stalnikowitz, D; López-Méndez, E; Malé-Velázquez, R; Marín-López, E; Mata-Marín, J A; Méndez-Sánchez, N; Monreal-Robles, R; Moreno-Alcántar, R; Muñoz-Espinosa, L; Navarro-Alvarez, S; Pavia-Ruz, N; Pérez-Ríos, A M; Poo-Ramírez, J L; Rizo-Robles, M T; Sánchez-Ávila, J F; Sandoval-Salas, R; Torre, A; Torres-Ibarra, R; Trejo-Estrada, R; Velarde-Ruiz Velasco, J A; Wolpert-Barraza, E; Bosques-Padilla, F

2018-05-23

The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Retinal dystrophies, genomic applications in diagnosis and prospects for therapy

PubMed Central

Nash, Benjamin M.; Wright, Dale C.; Grigg, John R.; Bennetts, Bruce

2015-01-01

Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. This review aims to demonstrate the high degree of genetic complexity in both the causative disease genes and their associated phenotypes, highlighting the more common clinical manifestation of retinitis pigmentosa (RP). The review also provides insight to recent advances in genomic molecular diagnosis and gene and cell-based therapies for the RDs. PMID:26835369

The Interaction Between Child Behavioral Inhibition and Parenting Behaviors: Effects on Internalizing and Externalizing Symptomology.

PubMed

Ryan, Sarah M; Ollendick, Thomas H

2018-02-20

Both child temperament and parenting have been extensively researched as predictors of child outcomes. However, theoretical models suggest that specific combinations of temperament styles and parenting behaviors are better predictors of certain child outcomes such as internalizing and externalizing symptoms than either temperament or parenting alone. The current qualitative review examines the interaction between one childhood temperamental characteristic (child behavioral inhibition) and parenting behaviors, and their subsequent impact on child psychopathology. Specifically, the moderating role of parenting on the relationship between child behavioral inhibition and both internalizing and externalizing psychopathology is examined, and the methodological variations which may contribute to inconsistent findings are explored. Additionally, support for the bidirectional relations between behavioral inhibition and parenting behaviors, as well as for the moderating role of temperament on the relationships between parenting and child outcomes, is briefly discussed. Finally, the clinical applicability of this overall conceptual model, specifically in regard to future research directions and potential clinical interventions, is considered.

Enhanced chemotherapeutic efficacy of apigenin liposomes in colorectal cancer based on flavone-membrane interactions.

PubMed

Banerjee, Kacoli; Banerjee, Shubhadeep; Mandal, Mahitosh

2017-04-01

Recent endeavors in exploiting vast array of natural phytochemicals to ameliorate colorectal cancer led us to investigate apigenin, a naturally occurring dietary flavone as a potential chemo-therapeutic agent. The present study focuses on establishing apigenin as a potential chemotherapeutic agent for alleviating colorectal cancer and reports the development of a stable liposomal nanocarrier with high encapsulation of the hydrophobic flavone apigenin for enhanced chemotherapeutic effects. The enhanced pharmacological activity of apigenin has been assigned to its ability to interact and subsequently influence membrane properties which also resulted in optimal yield of a stable, rigidified, non-leaky nano-carrier with ideal release kinetics. Extensive testing of drug and its liposomal counterpart for potential clinical chemotherapeutic applications yielded hemocompatibility and cytocompatibility with normal fibroblast cells while enhanced antineoplastic activity was observed in tumor xenograft model. The increased chemotherapeutic potential of liposomal apigenin highlights the clinical potential of apigenin-based vesicles. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of Magnetic Resonance Imaging and Three-Dimensional Treatment Planning in the Treatment of Orbital Lymphoma

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

Rudoltz, Marc S.; Ayyangar, Komanduri; Mohiuddin, Mohammed

Radiotherapy for lymphoma of the orbit must be individualized for each patient and clinical setting. Most techniques focus on optimizing the dose to the tumor while sparing the lens. This study describes a technique utilizing magnetic resonance imaging (MRI) and three dimensional (3D) planning in the treatment of orbital lymphoma. A patient presented with an intermediate grade lymphoma of the right orbit. The prescribed tumor dose was 4050 cGy in 18 fractions. Three D planning was carried out and tumor volumes, retina, and lens were subsequently outlined. Dose calculations including dose volume histograms of the target, retina, and lens weremore » then performed. Part of the retina was outside of the treatment volume while 50% of the retina received 90% or more of the prescribed dose. The patient was clinically NED when last seen 2 years following therapy with no treatment-related morbidity. Patients with lymphomas of the orbit can be optimally treated using MRI based 3D treatment planning.« less

Development of nonhuman adenoviruses as vaccine vectors

PubMed Central

Bangari, Dinesh S.; Mittal, Suresh K.

2006-01-01

Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclinical and clinical studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clinical use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addition to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination. PMID:16297508

Implant-supported Oral Rehabilitation in Child with Ectodermal Dysplasia - 4-year Follow-up.

PubMed

Cezária Triches, Thaisa; Ximenes, Marcos; Oliveira de Souza, João Gustavo; Rodrigues Lopes Pereira Neto, Armando; Cardoso, Antônio Carlos; Bolan, Michele

2017-01-01

Ectodermal dysplasia (ED) is an anomaly determined by genetic factors that alter ectodermal structures such as skin, hair, nails, glands, and teeth. Children affected by this condition require extensive, comprehensive, and multidisciplinary treatment. An 8-year-old female patient visited the Dentistry Clinic of the Federal University of Santa Catarina with the chief complaint of multiple missing teeth. The mother reported that the patient had ED. Clinical and radiographic examination revealed the congenital absence of several primary and permanent teeth and tooth germs. Subsequent oral rehabilitation comprised the application of a maxillary denture and mandibular implant-supported fixed prosthesis. The child was also supplied with a wig for further enhancement of esthetics aimed at improving her emotional wellbeing. Psychological follow-up and speech therapy were also provided. After 4 years of follow-up, implant-supported oral rehabilitation has proved to be a satisfactory treatment option, allowing restoration of masticatory, phonetic, and esthetic function, as well as an improvement in the patient's self-esteem and social wellbeing.

47 CFR 73.3518 - Inconsistent or conflicting applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Inconsistent or conflicting applications. 73... SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.3518 Inconsistent or conflicting applications. While an application is pending and undecided, no subsequent inconsistent or...

42 CFR 495.102 - Incentive payments to EPs.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) For 2018 and subsequent years, 97 percent, except as provided in paragraph (d)(3) of this section. (3) Decrease in applicable percent in certain circumstances. If, beginning CY 2018 and for each subsequent year...

Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice.

PubMed

Link, Jason M; Rich, Cathleen M; Korat, Maya; Burrows, Gregory G; Offner, Halina; Vandenbark, Arthur A

2007-04-01

Treatment of human autoimmune diseases such as multiple sclerosis (MS) will likely require agents that can prevent or reverse the inflammatory process that results in clinical relapses and disease progression. We evaluated the ability of a newly designed monomeric recombinant TCR ligand (RTL342M) containing HLA-DR2 peptide-binding domains covalently linked to MOG-35-55 peptide to prevent and treat both the initial episode and subsequent relapses of experimental autoimmune encephalomyelitis (EAE) in HLA-DR2 transgenic mice. Single doses of RTL342M given either i.v. or s.c. to HLA-DR2 mice produced a rapid (within 24 h) and dose-dependent reversal of clinical signs of paralytic EAE, and even a single dose < or = 2 microg could produce a significant treatment effect. Multiple daily doses were even more effective than the same total amount of RTL given as a single dose. By establishing the minimal effective dose, we determined that RTLs may be 50 times more potent than molar equivalent doses of myelin peptide alone. RTL342M given prior to induction of EAE prevented disease in most mice, and the remainder could be successfully retreated with RTL. Most important for clinical application, RTL342M was highly effective for treating EAE relapses when given periodically prior to the relapse or even after relapses had occurred. These data demonstrate the rapid and potent clinical effects of RTL342M at disease onset and during relapses in EAE and establish important principles governing the application of this novel approach as a possible therapy for patients with MS.

[(68)Ga-labeled peptides for clinical trials - production according to the German Drug Act: the Göttingen experience].

PubMed

Meller, Birgit; Angerstein, C; Liersch, T; Ghadimi, M; Sahlmann, C-O; Meller, J

2012-01-01

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.

A data-rich recruitment core to support translational clinical research.

PubMed

Kost, Rhonda G; Corregano, Lauren M; Rainer, Tyler-Lauren; Melendez, Caroline; Coller, Barry S

2015-04-01

Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. For protocols receiving recruitment services during 2009-2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first-time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real-time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. © 2014 Wiley Periodicals, Inc.

A Data‐Rich Recruitment Core to Support Translational Clinical Research

PubMed Central

Corregano, Lauren M.; Rainer, Tyler‐Lauren; Melendez, Caroline; Coller, Barry S.

2014-01-01

Abstract Background Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. Methods The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. Results For protocols receiving recruitment services during 2009–2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first‐time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Conclusions Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real‐time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. PMID:25381717

Fully automatized renal parenchyma volumetry using a support vector machine based recognition system for subject-specific probability map generation in native MR volume data

NASA Astrophysics Data System (ADS)

Gloger, Oliver; Tönnies, Klaus; Mensel, Birger; Völzke, Henry

2015-11-01

In epidemiological studies as well as in clinical practice the amount of produced medical image data strongly increased in the last decade. In this context organ segmentation in MR volume data gained increasing attention for medical applications. Especially in large-scale population-based studies organ volumetry is highly relevant requiring exact organ segmentation. Since manual segmentation is time-consuming and prone to reader variability, large-scale studies need automatized methods to perform organ segmentation. Fully automatic organ segmentation in native MR image data has proven to be a very challenging task. Imaging artifacts as well as inter- and intrasubject MR-intensity differences complicate the application of supervised learning strategies. Thus, we propose a modularized framework of a two-stepped probabilistic approach that generates subject-specific probability maps for renal parenchyma tissue, which are refined subsequently by using several, extended segmentation strategies. We present a three class-based support vector machine recognition system that incorporates Fourier descriptors as shape features to recognize and segment characteristic parenchyma parts. Probabilistic methods use the segmented characteristic parenchyma parts to generate high quality subject-specific parenchyma probability maps. Several refinement strategies including a final shape-based 3D level set segmentation technique are used in subsequent processing modules to segment renal parenchyma. Furthermore, our framework recognizes and excludes renal cysts from parenchymal volume, which is important to analyze renal functions. Volume errors and Dice coefficients show that our presented framework outperforms existing approaches.

A threshold dose distribution approach for the study of PDT resistance development: A threshold distribution approach for the study of PDT resistance.

PubMed

de Faria, Clara Maria Gonçalves; Inada, Natalia Mayumi; Vollet-Filho, José Dirceu; Bagnato, Vanderlei Salvador

2018-05-01

Photodynamic therapy (PDT) is a technique with well-established principles that often demands repeated applications for sequential elimination of tumor cells. An important question concerns the way surviving cells from a treatment behave in the subsequent one. Threshold dose is a core concept in PDT dosimetry, as the minimum amount of energy to be delivered for cell destruction via PDT. Concepts of threshold distribution have shown to be an important tool for PDT results analysis in vitro. In this study, we used some of these concepts for demonstrating subsequent treatments with partial elimination of cells modify the distribution, which represents an increased resistance of the cells to the photodynamic action. HepG2 and HepaRG were used as models of tumor and normal liver cells and a protocol to induce resistance, consisted of repeated PDT sessions using Photogem® as a photosensitizer, was applied to the tumor ones. The response of these cells to PDT was assessed using a standard viability assay and the dose response curves were used for deriving the threshold distributions. The changes in the distribution revealed that the resistance protocol effectively eliminated the most sensitive cells. Nevertheless, HepaRG cell line was the most resistant one among the cells analyzed, which indicates a specificity in clinical applications that enables the use of high doses and drug concentrations with minimal damage to the surrounding normal tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Fully automatized renal parenchyma volumetry using a support vector machine based recognition system for subject-specific probability map generation in native MR volume data.

PubMed

Gloger, Oliver; Tönnies, Klaus; Mensel, Birger; Völzke, Henry

2015-11-21

In epidemiological studies as well as in clinical practice the amount of produced medical image data strongly increased in the last decade. In this context organ segmentation in MR volume data gained increasing attention for medical applications. Especially in large-scale population-based studies organ volumetry is highly relevant requiring exact organ segmentation. Since manual segmentation is time-consuming and prone to reader variability, large-scale studies need automatized methods to perform organ segmentation. Fully automatic organ segmentation in native MR image data has proven to be a very challenging task. Imaging artifacts as well as inter- and intrasubject MR-intensity differences complicate the application of supervised learning strategies. Thus, we propose a modularized framework of a two-stepped probabilistic approach that generates subject-specific probability maps for renal parenchyma tissue, which are refined subsequently by using several, extended segmentation strategies. We present a three class-based support vector machine recognition system that incorporates Fourier descriptors as shape features to recognize and segment characteristic parenchyma parts. Probabilistic methods use the segmented characteristic parenchyma parts to generate high quality subject-specific parenchyma probability maps. Several refinement strategies including a final shape-based 3D level set segmentation technique are used in subsequent processing modules to segment renal parenchyma. Furthermore, our framework recognizes and excludes renal cysts from parenchymal volume, which is important to analyze renal functions. Volume errors and Dice coefficients show that our presented framework outperforms existing approaches.

Novel tool for deprescribing in chronic patients with multimorbidity: List of Evidence-Based Deprescribing for Chronic Patients criteria.

PubMed

Rodríguez-Pérez, Aitana; Alfaro-Lara, Eva Rocío; Albiñana-Perez, Sandra; Nieto-Martín, María Dolores; Díez-Manglano, Jesús; Pérez-Guerrero, Concepción; Santos-Ramos, Bernardo

2017-11-01

To create a tool to identify drugs and clinical situations that offers an opportunity of deprescribing in patients with multimorbidity. A literature review completed with electronic brainstorming, and subsequently, a panel of experts using the Delphi methodology were applied. The experts assessed the criteria identified in the literature and brainstorming as possible situations for deprescribing. They were also asked to assess the influence of life prognosis in each criterion. A tool was composed of the most appropriate criteria according to the strength of their evidence, usefulness in patients with multimorbidity and applicability in clinical practice. Out of a total of 100, 27 criteria were selected to be included in the final list. It was named the LESS-CHRON criteria (List of Evidence-baSed depreScribing for CHRONic patients), and was organized by the anatomical group of the Anatomical, Therapeutic, Chemical (ATC) classification system of the drug to be deprescribed. Each criterion contains: drug indication for which it is prescribed, clinical situation that offers an opportunity to deprescribe, clinical variable to be monitored and the minimum time to follow up the patient after deprescribing. The "LESS-CHRON criteria" are the result of a comprehensive and standardized methodology to identify clinical situations for deprescribing drugs in chronic patients with multimorbidity. Geriatr Gerontol Int 2017; 17: 2200-2207. © 2017 Japan Geriatrics Society.

Oncolytic Virus Therapy of Glioblastoma Multiforme – Concepts and Candidates

PubMed Central

Wollmann, Guido; Ozduman, Koray; van den Pol, Anthony N.

2012-01-01

Twenty years of oncolytic virus (OV) development have created a field that is driven by the potential promise of lasting impact on our cancer treatment repertoire. With the field constantly expanding – over 20 viruses have been recognized as potential OVs – new virus candidates continue to emerge even as established viruses reach clinical trials. They all share the defining commonalities of selective replication in tumors, subsequent tumor cell lysis, and dispersion within the tumor. Members from diverse virus classes with distinctly different biologies and host species have been identified. Of these viruses, 15 have been tested on human glioblastoma multiforme (GBM). So far, 20 clinical trials have been conducted or initiated using attenuated strains of 7 different oncolytic viruses against GBM. In this review, we present an overview of viruses that have been developed or considered for GBM treatment. We outline the principles of tumor targeting and selective viral replication, which include mechanisms of tumor-selective binding, and molecular elements usurping cellular biosynthetic machinery in transformed cells. Results from clinical trials have clearly established the proof of concept and have confirmed the general safety of OV application in the brain. The moderate clinical efficacy has not yet matched the promising preclinical lab results; next-generation OVs that are either “armed” with therapeutic genes or that are embedded in a multimodality treatment regimen should enhance the clinical results. PMID:22290260

Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery.

PubMed

Carlson, Brett L; Pokorny, Jenny L; Schroeder, Mark A; Sarkaria, Jann N

2011-03-01

Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important for advancement of basic and translational biology. One model that has gained wide acceptance in the neuro-oncology community is the primary xenograft model. This model entails the engraftment of patient tumor specimens into the flank of nude mice and subsequent serial passage of these tumors in the flank of mice. These tumors are then used to establish short-term explant cultures or intracranial xenografts. This unit describes detailed procedures for establishment, maintenance, and utilization of a primary GBM xenograft panel for the purpose of using them as tumor models for basic or translational studies.

Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry: In Situ Molecular Mapping

PubMed Central

Angel, Peggi M.; Caprioli, Richard M.

2013-01-01

Matrix-assisted laser desorption ionization imaging mass spectrometry (IMS) is a relatively new imaging modality that allows mapping of a wide range of biomolecules within a thin tissue section. The technology uses a laser beam to directly desorb and ionize molecules from discrete locations on the tissue that are subsequently recorded in a mass spectrometer. IMS is distinguished by the ability to directly measure molecules in situ ranging from small metabolites to proteins, reporting hundreds to thousands of expression patterns from a single imaging experiment. This article reviews recent advances in IMS technology, applications, and experimental strategies that allow it to significantly aid in the discovery and understanding of molecular processes in biological and clinical samples. PMID:23259809

Germline genome-editing research and its socioethical implications.

PubMed

Ishii, Tetsuya

2015-08-01

Genetically modifying eggs, sperm, and zygotes ('germline' modification) can impact on the entire body of the resulting individual and on subsequent generations. With the advent of genome-editing technology, human germline gene modification is no longer theoretical. Owing to increasing concerns about human germline gene modification, a voluntary moratorium on human genome-editing research and/or the clinical application of human germline genome editing has recently been called for. However, whether such research should be suspended or encouraged warrants careful consideration. The present article reviews recent research on mammalian germline genome editing, discusses the importance of public dialogue on the socioethical implications of human germline genome-editing research, and considers the relevant guidelines and legislation in different countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: are two applications better than one?

PubMed

Smith, Marshall E; Elstad, Mark

2009-02-01

Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short-term improvement, is often associated with long-term relapse. Mitomycin-C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3-6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application. A randomized, prospective, double-blind, placebo-controlled clinical trial. Twenty-six patients with laryngotracheal stenosis due to idiopathic subglottic stenosis, postintubation stenosis, or Wegener's granulomatosis entered a protocol to receive three endoscopic CO(2) laser and dilation procedures over a 3-month interval. At the first procedure, after radial CO(2) laser incision and airway dilation, all patients received topical application of MMC (0.5 mg/mL) to the airway lesion. One month later, a second endoscopic incision and dilation was performed and the patients were randomized to either a second application of mitomycin-C or to application of saline placebo. A third dilation procedure was performed 2 months later, without MMC application. Patients were followed for up to 5 years for relapse of airway stenosis with clinical symptoms sufficient to require a subsequent procedure. The relapse rates at 1, 3, and 5 years were 7%, 36%, and 69% for patients treated with two applications of MMC compared to 33%, 58%, and 70% for patients treated with one application of MMC. The median interval to relapse was 3.8 years in the two-application group, compared with 2.4 years in the one-application group. This prospective randomized double-blind placebo-controlled trial suggests that, in the endoscopic management of laryngotracheal stenosis, two applications of MMC given 3-4 weeks apart after airway radial incision and dilation reduces the restenosis rate for 2 to 3 years after treatment when compared to a single application. However, restenosis and delayed symptom recurrence continues so that at 5 years the relapse rates are the same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic stenosis in the majority of patients.

Measurement standards for interdisciplinary medical rehabilitation.

PubMed

Johnston, M V; Keith, R A; Hinderer, S R

1992-12-01

Rehabilitation must address problems inherent in the measurement of human function and health-related quality of life, as well as problems in diagnosis and measurement of impairment. This educational document presents an initial set of standards to be used as guidelines for development and use of measurement and evaluation procedures and instruments for interdisciplinary, health-related rehabilitation. Part I covers general measurement principles and technical standards, beginning with validity, the central consideration for use of measures. Subsequent sections focus on reliability and errors of measurement, norms and scaling, development of measures, and technical manuals and guides. Part II covers principles and standards for use of measures. General principles of application of measures in practice are discussed first, followed by standards to protect persons being measured and then by standards for administrative applications. Many explanations, examples, and references are provided to help professionals understand measurement principles. Improved measurement will ensure the basis of rehabilitation as a science and nourish its success as a clinical service.

Comparison between multislice and cone-beam computerized tomography in the volumetric assessment of cleft palate.

PubMed

Albuquerque, Marco Antonio; Gaia, Bruno Felipe; Cavalcanti, Marcelo Gusmão Paraíso

2011-08-01

The aim of this study was to determine the applicability of multislice and cone-beam computerized tomography (CT) in the assessment of bone defects in patients with oral clefts. Bone defects were produced in 9 dry skulls to mimic oral clefts. All defects were modeled with wax. The skulls were submitted to multislice and cone-beam CT. Subsequently, physical measurements were obtained by the Archimedes principle of water displacement of wax models. The results demonstrated that multislice and cone-beam CT showed a high efficiency rate and were considered to be effective for volumetric assessment of bone defects. It was also observed that both CT modalities showed excellent results with high reliability in the study of the volume of bone defects, with no difference in performance between them. The clinical applicability of our research has shown these CT modalities to be immediate and direct, and they is important for the diagnosis and therapeutic process of patients with oral cleft. Copyright © 2011 Mosby, Inc. All rights reserved.

77 FR 1917 - Madrid Protocol

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... an International Registration) using the Trademark Electronic Application System (TEAS), which is... hours Application for International Registration (PTO- 15 minutes 3,900 975 2131 TEAS). Application for... minutes 400 100 2132 TEAS). Application for Subsequent Designation (paper, 20 minutes 5 2 no form...

Resilience Mediates the Longitudinal Relationships Between Social Support and Mental Health Outcomes in Multiple Sclerosis.

PubMed

Koelmel, Emily; Hughes, Abbey J; Alschuler, Kevin N; Ehde, Dawn M

2017-06-01

To investigate the longitudinal relationships between social support and subsequent mental health outcomes in individuals with multiple sclerosis (MS), and to examine resilience as a mediator between social support and subsequent mental health outcomes in this population. Observational, longitudinal cohort study. Participants were assessed at 4 time points over 12 months in the context of a previously reported randomized controlled trial. Telephone-based measures administered to community-based participants. Individuals (N=163) with MS and 1 or more of the following symptoms: depression, fatigue, and pain. Not applicable. Mental health outcomes included (1) depressive symptomatology, assessed using the Patient Health Questionnaire-9; (2) anxious symptomatology, assessed using the short form of the Emotional Distress-Anxiety Scale from the Patient-Reported Outcomes Measurement Information System; and (3) general mental health status, assessed using the Mental Component Summary score from the Short Form-8 Health Survey. Resilience was assessed using the Connor-Davidson Resilience Scale. At any given time, social support from significant others, family members, and friends was significantly associated with subsequent mental health outcomes for all 3 measures assessed (all P values <.05). Resilience measured concomitantly with social support significantly mediated the relationships between social support and subsequent mental health outcomes. After controlling for resilience, most of the direct relationships between social support and mental health outcomes were no longer significant. There are significant longitudinal relationships between social support, resilience, and mental health outcomes for people with MS. Given the mediating role of resilience in supporting better mental health outcomes, future clinical research and practice may benefit from an emphasis on resilience-focused psychological interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. All rights reserved.

Diagnostic application of clinical exome sequencing in Leber congenital amaurosis.

PubMed

Han, Jinu; Rim, John Hoon; Hwang, In Sik; Kim, Jieun; Shin, Saeam; Lee, Seung-Tae; Choi, Jong Rak

2017-01-01

Leber congenital amaurosis (LCA) is a hereditary retinal dystrophy with wide genetic heterogeneity. Next-generation sequencing (NGS) targeting multiple genes can be a good option for the diagnosis of LCA, and we tested a clinical exome panel in patients with LCA. A total of nine unrelated Korean patients with LCA were sequenced using the Illumina TruSight One panel, which targets 4,813 clinically associated genes, followed by confirmation using Sanger sequencing. Patients' clinical information and familial study results were obtained and used for comprehensive interpretation. In all nine patients, we identified pathogenic variations in LCA-associated genes: NMNAT1 (n=3), GUCY2D (n=2), RPGRIP1 (n=2), CRX (n=1), and CEP290 or SPATA7 . Six patients had one or two mutations in accordance with inheritance patterns, all consistent with clinical phenotypes. Two patients had only one pathogenic mutation in recessive genes ( NMNAT1 and RPGRIP1 ), and the clinical features were specific to disorders associated with those genes. Six patients were solved for genetic causes, and it remains unclear for three patients with the clinical exome panel. With subsequent targeted panel sequencing with 113 genes associated with infantile nystagmus syndrome, a likely pathogenic allele in CEP290 was detected in one patient. Interestingly, one pathogenic variant (p.Arg237Cys) in NMNAT1 was present in three patients, and it had a high allele frequency (0.24%) in the general Korean population, suggesting that NMNAT1 could be a major gene responsible for LCA in Koreans. We confirmed that a commercial clinical exome panel can be effectively used in the diagnosis of LCA. Careful interpretation and clinical correlation could promote the successful implementation of clinical exome panels in routine diagnoses of retinal dystrophies, including LCA.

Clinical evaluation of the Novacor totally implantable ventricular assist system. Current status.

PubMed

Daniel, M A; Lee, J; LaForge, D H; Chen, H; Billich, J; Miller, P J; Ramasamy, N; Strauss, L R; Jassawalla, J S; Portner, P M

1991-01-01

The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH-sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application-specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval.

Development and future perspectives of behavioral medicine in Japan.

PubMed

Nomura, Shinobu

2016-01-01

Development and Future Perspectives of Behavioral Medicine in Japan The study of the "Type A behavior pattern and myocardial infarction" was one of the main themes in the early stage of Behavioral Medicine. After that, behavior modification came to be widely applied to the treatment of various kinds of chronic diseases, and a general concept of Behavioral Medicine was subsequently formed. The Japanese Society of Behavioral Medicine was established in 1992 and is comprised of researchers in the fields of clinical medicine, social medicine, and psycho-behavioral science. Recently, we devised a core curriculum for behavioral science and behavioral medicine and have published a Japanese version of the "Textbook of Behavioral Medicine" in conformity with it. It is a primer that includes all of the basics and clinical applications of Behavioral Medicine and is edited as a manual that can be utilized in clinical practice. We hope this book will contribute to the development of Behavioral Medicine in Japan, to a more healthy life for our people, and to the improvement of the QOL of our patients. In this paper, I discuss the future perspectives from my personal opinion while looking back on the history of Behavioral Medicine in Japan.

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

Translational Challenges in Cardiovascular Tissue Engineering.

PubMed

Emmert, Maximilian Y; Fioretta, Emanuela S; Hoerstrup, Simon P

2017-04-01

Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions. To overcome this problem, the concept of tissue engineering (TE) has been repeatedly suggested as a potential technology to enable native-like cardiovascular replacements with regenerative and growth capacities, suitable for young adults and children. However, despite promising data from pre-clinical and first clinical pilot trials, the translation and clinical relevance of such TE technologies is still very limited. The reasons that currently limit broad clinical adoption are multifaceted and comprise of scientific, clinical, logistical, technical, and regulatory challenges which need to be overcome. The aim of this review is to provide an overview about the translational problems and challenges in current TE approaches. It further suggests directions and potential solutions on how these issues may be efficiently addressed in the future to accelerate clinical translation. In addition, a particular focus is put on the current regulatory guidelines and the associated challenges for these promising TE technologies.

Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program.

PubMed

Jones, Craig A; Clement, Loran T; Morphew, Tricia; Kwong, Kenny Yat Choi; Hanley-Lopez, Jean; Lifson, Francene; Opas, Lawrence; Guterman, Jeffrey J

2007-06-01

National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.

Chronic histiocytic intervillositis - Clinical, biochemical and radiological findings: An observational study.

PubMed

Koby, Lawrence; Keating, Sarah; Malinowski, Ann Kinga; D'Souza, Rohan

2018-04-01

Chronic histiocytic intervillositis (CHI) of the placenta although rare, has a high recurrence rate, is associated with serious adverse pregnancy outcomes and has no available treatment. This study aims to determine clinical, biochemical and radiological factors associated with CHI, to guide management of subsequent pregnancies. This retrospective observational study included consecutive cases with a histopathologic diagnosis of CHI after 18 weeks of gestation, between 2001 and 2014, and no controls. Clinical (maternal, fetal and delivery outcomes), biochemical (first- and second-trimester biomarkers for fetal aneuploidy and serum alkaline phosphatase) and radiological (second- and third-trimester fetal, placental and Doppler ultrasound) factors associated with a histopathological diagnosis of CHI were identified and results presented as percentages. Outcomes of subsequent pregnancies were described. Of 231 identified cases of 'intervillositis', 33 were confirmed to have CHI, of which only 4/33 (12.1%) had prior uncomplicated term deliveries. During pregnancy, 10/18 (55.5%) had abnormal first-trimester screening, 4/16 (25%) had abnormal second-trimester screening, 6/19 (31.6%) had at least one elevated alkaline phosphatase level, and 15/20 (75%) had at least one abnormal feature on mid-trimester placental ultrasound. In subsequent pregnancies that were closely followed with a combination of biochemical and radiologic tests, there were no cases of fetal loss, and lower incidence of fetal growth restriction and preterm birth. No clinical, biochemical or radiological finding is consistently associated with CHI and adverse outcomes thereof. Whether the incorporation of these tests in individualized care-plans could improve outcomes in subsequent pregnancies needs to be studied further. Copyright © 2018 Elsevier Ltd. All rights reserved.

Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

PubMed

de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

2017-04-01

Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (<75 yr) patient subgroups. Data were collected at the final OS analysis (96% of expected death events). Subsequent therapy data were prospectively collected, while response and discontinuation data were collected retrospectively following discontinuation of the study drug. At the discretion of the investigator, 67% (365/546) of patients from the AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced prostate cancer whose disease progressed after treatment with abiraterone acetate. Older patients were less likely to be treated with subsequent therapy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prevention of oral food allergy sensitization via skin application of food allergen in a mouse model.

PubMed

Li, W; Zhang, Z; Saxon, A; Zhang, K

2012-05-01

Treatment options for food allergy remain limited. Development of novel approaches for the prevention and/or treatment of severe peanut allergy and other food allergies is urgently needed. The objective of this study was to test whether skin application of food allergen can be used as a prophylactic and/or therapeutic intervention for food allergy. Balb/C mice were given 5 weekly cutaneous application of complete peanut extract (CPE) or ovalbumin (OVA) ranging from 10 to 1000 μg on the shaved back skin, followed by 5 weekly treatments with oral CPE or OVA plus cholera toxin to induce allergic reactivity to the food. At various time points, the immunologic responses and allergic clinical manifestations to allergens were examined. Skin application of a 10-1000 μg dose of CPE or OVA to structurally intact skin did not lead to allergic sensitization to peanut or OVA. Rather, cutaneous allergen application blocked, in a dose-dependent fashion, the subsequent induction of the oral sensitization including inhibiting oral sensitization-induced CPE-specific IgE, IgG1, and IgG2a production, suppressing the peanut anaphylaxis, and modulating the oral sensitization-promoted cytokine production. The cutaneous OVA application also resulted in similar results as seen with CPE application. Cutaneous application of intact skin with peanut or OVA can block the development of orally induced corresponding food allergies, suggesting that allergic tolerance to peanuts and OVA might be achieved via allergen cutaneous application. © 2012 John Wiley & Sons A/S.

An mHealth App for Decision-Making Support in Wound Dressing Selection (WounDS): Protocol for a User-Centered Feasibility Study.

PubMed

Jordan, Scott; McSwiggan, Jane; Parker, Joanne; Halas, Gayle A; Friesen, Marcia

2018-04-24

Primary care health professionals, especially family physicians, see a variety of wounds, and yet-despite the frequency of providing wound care-many family physicians do not feel confident in wound care management. This is partly due to a lack of formal wound education in Family Medicine programs. While there are numerous electronic wound care resources available in the UK and North America, none were identified that address the specific need in supporting clinical decision-making in wound dressing selection. At the same time, healthcare providers are increasingly using technology in personal and professional contexts, and a logical extension is to use technology for knowledge translation strategies. This work developed a prototype mobile health software application named WounDS, designed to support clinical decision-making in selecting wound dressings. This article presents the development and evaluation plan for the WounDS app. WounDS has been developed on the iOS platform. The primary specification included ease of use, in that one of the primary influences in user adoption would be the ability to receive a wound dressing recommendation in under 30 seconds and under 5 taps on the screen. The WounDS app guides users through a series of binary decisions for assessing the wound and provides a wound dressing recommendation. The selection algorithm is based in best practices using the Wound Bed Preparation Paradigm. Current work is underway to examine the implementation needs for WounDS to be most effectively utilized and to pilot test its feasibility and use in clinical care. Data will be collected through user trials, focus groups, and user metadata will be collected within the app. Optimizing these preconditions will enable a subsequent phase of study to determine effects on clinical decision-making and clinical outcomes. WounDS is designed for knowledge translation, use of technology in clinical decision-making, and continuity of care. The benefits of WounDS include the potential to improve healthcare providers' competency in wound management and to improve wound healing through better alignment with evidence-based best practices in wound dressing selection, consistency in care from primary to community care, and subsequent downstream impacts in quality of life for patients. ©Scott Jordan, Jane McSwiggan, Joanne Parker, Gayle A. Halas, Marcia Friesen. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 24.04.2018.

In vivo characterization of structural changes after topical application of glucocorticoids in healthy human skin

NASA Astrophysics Data System (ADS)

Jung, Sora; Lademann, Jürgen; Darvin, Maxim E.; Richter, Claudia; Pedersen, Claus Bang; Richter, Heike; Schanzer, Sabine; Kottner, Jan; Blume-Peytavi, Ulrike; Røpke, Mads Almose

2017-07-01

Topical glucocorticoids (GC) are known to induce changes in human skin with the potential to develop skin atrophy. Here, atrophogenic effects and subsequent structural changes in the skin after topical application of GC were investigated in vivo. Sixteen healthy volunteers were topically treated daily on the forearms with clobetasol propionate, betamethasone dipropionate, and the petrolatum vehicle for 4 weeks. All treated skin areas and a nontreated control area were examined by ultrasound, optical coherence tomography, confocal laser scanning microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at baseline 1 day after last application and 1 week after last application. Investigated parameters included stratum corneum thickness, epidermal, and full skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm ratio, skin surface classification, relative collagen and elastin signal intensity, second-harmonic generation-to-autofluorescence aging index of dermis (SAAID), and the antioxidant status of the skin. A reduction in epidermal and dermal skin thickness was observed in GC treated as well as in vehicle-treated and untreated skin areas on the volar forearm. MPT analysis showed an increased epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a significant increase of SAAID after GC treatment indicating a restructuring or compression of collagen fibers clinically being observed as atrophic changes.

Improving efficiency and saving money in an otolaryngology urgent referral clinic.

PubMed

Ibrahim, Nader; Virk, Jagdeep; George, Jason; Elmiyeh, Behrad; Singh, Arvind

2015-06-16

A closed loop audit of the ear nose and throat (ENT) urgent referral clinic at a London hospital was conducted assessing the number of patients reviewed, referral source, appropriateness of referral, presenting complaint and assigned follow-up appointments. Data was sourced from clinic letters and the patient appointment system over a 3-mo period. The initial cycle analysed 490 patients and the subsequent cycle 396. The initial audit yielded clinically relevant and cost effective recommendations which were implemented, and the audit cycle was subsequently repeated. The re-audit demonstrated decreased clinic numbers from an average 9.8 to 7.2 patients per clinic, in keeping with ENT United Kingdom guidelines. A 21% decrease in patient follow-up and 13% decrease in inappropriate referrals was achieved. Direct bookings into outpatient clinics decreased by 8%, due to correct referral pathway utilisation. Comparisons of all data sets were found to show statistical significance P < 0.05. We reported a total financial saving of £32490 in a period of 3 mo (£590 per clinic). We demonstrated that simple guidelines, supervision and consultant-led education which are non-labour intensive can have a significant impact on service provision and cost.

Effects of ward rotation on subsequent transition processes of Japanese clinical nurses.

PubMed

Fujino, Mitsuku; Nojima, Yoshiko

2005-03-01

The purpose of this study was to examine the experience of Japanese clinical nurses undertaking a ward rotation in a general hospital, and its effects on subsequent processes relating to: (i) perception of ward rotation; (ii) reactions to the ward transition process; and (iii) outcomes of ward rotation. In-depth interviews were conducted with 21 Japanese clinical nurses who had an average of 8.8 years (SD = 5.50) clinical experience. Findings indicated that participants experienced role overload, role incongruity and/or role underload, role overqualification, or role ambiguity in the new environment. These role stresses created critical emotional distress during the transition process. The high desire for career development facilitated the transition process, while lack of preparation inhibited the transition process. To facilitate smooth transition, well-prepared and structured supports based on reliable interpersonal relationships are necessary. The findings offer significant cues for effective ward rotation programs. The implication for nursing administrators is that appropriate ward rotations enhance confidence and promote effective role development in the new clinical setting.

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

PubMed Central

Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

2016-01-01

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia. PMID:27242415

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.

PubMed

Lytvyn, Yuliya; Bjornstad, Petter; Udell, Jacob A; Lovshin, Julie A; Cherney, David Z I

2017-10-24

Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor. The CANVAS trial (Canagliflozin Cardiovascular Assessment Study) subsequently reported a reduction in 3-point major adverse cardiovascular events and HF hospitalization risk. Although SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, and decreases in blood pressure, arterial stiffness, and afterload as well, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients who have HF with and without T2D. Accordingly, in this review, we summarize the key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence that support the rationale for the use of SGLT2 inhibitors in patients with HF who have T2D. Because these favorable effects presumably occur independent of blood glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors. © 2017 American Heart Association, Inc.

A Facile Method to Establish Human Induced Pluripotent Stem Cells From Adult Blood Cells Under Feeder-Free and Xeno-Free Culture Conditions: A Clinically Compliant Approach

PubMed Central

Chou, Bin-Kuan; Gu, Haihui; Gao, Yongxing; Dowey, Sarah N.; Wang, Ying; Shi, Jun; Li, Yanxin; Ye, Zhaohui; Cheng, Tao

2015-01-01

Reprogramming human adult blood mononuclear cells (MNCs) cells by transient plasmid expression is becoming increasingly popular as an attractive method for generating induced pluripotent stem (iPS) cells without the genomic alteration caused by genome-inserting vectors. However, its efficiency is relatively low with adult MNCs compared with cord blood MNCs and other fetal cells and is highly variable among different adult individuals. We report highly efficient iPS cell derivation under clinically compliant conditions via three major improvements. First, we revised a combination of three EBNA1/OriP episomal vectors expressing five transgenes, which increased reprogramming efficiency by ≥10–50-fold from our previous vectors. Second, human recombinant vitronectin proteins were used as cell culture substrates, alleviating the need for feeder cells or animal-sourced proteins. Finally, we eliminated the previously critical step of manually picking individual iPS cell clones by pooling newly emerged iPS cell colonies. Pooled cultures were then purified based on the presence of the TRA-1-60 pluripotency surface antigen, resulting in the ability to rapidly expand iPS cells for subsequent applications. These new improvements permit a consistent and reliable method to generate human iPS cells with minimal clonal variations from blood MNCs, including previously difficult samples such as those from patients with paroxysmal nocturnal hemoglobinuria. In addition, this method of efficiently generating iPS cells under feeder-free and xeno-free conditions allows for the establishment of clinically compliant iPS cell lines for future therapeutic applications. PMID:25742692

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

PubMed

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Echocardiographic estimation of left atrial pressure in beagle dogs with experimentally-induced mitral valve regurgitation.

PubMed

Ishikawa, Taisuke; Fukushima, Ryuji; Suzuki, Shuji; Miyaishi, Yuka; Nishimura, Taiki; Hira, Satoshi; Hamabe, Lina; Tanaka, Ryou

2011-08-01

Non-invasive and immediate estimation of left atrial pressure (LAP) is very useful for the management of mitral regurgitation (MR), and many reports have assessed echocardiographic estimations of LAP to date. However, it has been unclear of which examination and evaluate article possess the best accuracy for the MR severity. The present research aims to establish the echocardiographic estimation equation of LAP that is well applicable for clinical MR dogs. After the chordae tendineae rupture was experimentally induced via left atriotomy in six healthy beagle dogs (three males and three females, two years old, weighing between 9.8 to 12.8 kg), a radio telemetry transmitter catheter was inserted, which allows the continuous recordings of LAP without the use of sedation. Approximately 5 weeks after the surgery, echocardiographic examination, indirect blood pressure measurement, measurement of plasma atrial natriuretic peptide (ANP) and LAP measurement by way of the radio telemetry system was performed simultaneously. Subsequently, simple linear regression equations between LAP and each variable were obtained, and the equations were evaluated whether to be applicable for clinical MR dogs. As a result, the ratio of early diastolic mitral flow to early diastolic lateral mitral annulus velocity (E/Ea) had the strongest correlation as maximum LAP=7.03*(E/Ea)-54.86 (r=0.74), and as mean LAP=4.94*(E/Ea)-40.37 (r=0.70) among the all variables. Therefore, these two equations associated with E/Ea should bring more precise and instant estimations of maximum and mean LAP in clinical MR dogs.

Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

PubMed Central

Gill, Katherine L.; Gertz, Michael; Houston, J. Brian

2013-01-01

A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro–in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

Clinical response and safety of malathion shampoo for treatment of head lice in a primary school.

PubMed

Wananukul, Siriwan; Chatproedprai, Susheera; Tempark, Therdpong; Wananukul, Winai

2011-04-01

Help eradicate or at least alleviating head lice in a primary school with malathion shampoo and to study clinical response and safety of malathion shampoo. All students were examined by using a fine-toothed lice comb to help detect live lice. Direct visual examination and the collection of nits for microscopic examination were performed to differentiate viable nits from empty nits. Diagnosis of head lice was made by the presence of lice. All students that had lice and/or nits were treated with malathion shampoo. Malathion shampoo was also provided for all family members. Pediculocidal efficacy was by the presence or absence of live lice. Blood for red blood cell cholinesterase activity was drawn in 32 volunteers before treatment and after the second treatment. At the first visit, 629 students were examined and 48 students had live head lice. The infestation rate was 13% in girls and 1.3% in boys. The cure rate was 93% after the first treatment. The reported side effects were nausea, a burning sensation, and irritation that was found in five (4%), 10 (7%) and three (2%) students respectively. The mean of RBC cholinesterase activity before and after two applications showed significant changes (p = 0.03). It was -7.5 +/- 4.1% reduction from the initial, but all were in the normal range. There was no report of clinical manifestation of malathion toxicity. Malathion shampoo is safe and effective in the treatment of head lice. There is significant skin absorption so a scalp examination for head lice should be done before subsequent application to avoid unnecessary exposure.

Improving client satisfaction and clinic revenues through systems simulation: the case of a university nutrition clinic.

PubMed

Thompson, R C; Scammon, D L

1994-01-01

A client-responsive strategy was developed based upon input from nutrition clinic personnel, administrators, and clients. Systems simulation identified the strategy most likely to lead to client satisfaction while also meeting the needs of clinic personnel and administration. The strategy was subsequently introduced into the clinic and patient satisfaction and operating revenues were monitored following implementation. Both measures of impact demonstrated significant improvement.

Automated tumor analysis for molecular profiling in lung cancer

PubMed Central

Boyd, Clinton; James, Jacqueline A.; Loughrey, Maurice B.; Hougton, Joseph P.; Boyle, David P.; Kelly, Paul; Maxwell, Perry; McCleary, David; Diamond, James; McArt, Darragh G.; Tunstall, Jonathon; Bankhead, Peter; Salto-Tellez, Manuel

2015-01-01

The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics. PMID:26317646

The effects of expanding outpatient and inpatient evaluation and management services in a pediatric interventional radiology practice.

PubMed

Edalat, Faramarz; Lindquester, Will S; Gill, Anne E; Simoneaux, Stephen F; Gaines, Jennifer; Hawkins, C Matthew

2017-03-01

Despite a continuing emphasis on evaluation and management clinical services in adult interventional radiology (IR) practice, the peer-reviewed literature addressing these services - and their potential economic benefits - is lacking in pediatric IR practice. To measure the effects of expanding evaluation and management (E&M) services through the establishment of a dedicated pediatric interventional radiology outpatient clinic and inpatient E&M reporting system. We collected and analyzed E&M current procedural terminology (CPT) codes from all patients seen in a pediatric interventional radiology outpatient clinic between November 2014 and August 2015. We also calculated the number of new patients seen in the clinic who had a subsequent procedure (procedural conversion rate). For comparison, we used historical data comprising pediatric patients seen in a general interventional radiology (IR) clinic for the 2 years immediately prior. An inpatient E&M reporting system was implemented and all inpatient E&M (and subsequent procedural) services between July 2015 and September 2015 were collected and analyzed. We estimated revenue for both outpatient and inpatient services using the Medicare Physician Fee Schedule global non-facility price as a surrogate. Following inception of a pediatric IR clinic, the number of new outpatients (5.5/month; +112%), procedural conversion rate (74.5%; +19%), estimated E&M revenue (+158%), and estimated procedural revenue from new outpatients (+228%) all increased. Following implementation of an inpatient clinic reporting system, there were 8.3 consults and 7.3 subsequent hospital encounters per month, with a procedural conversion rate of 88%. Growth was observed in all meaningful metrics following expansion of outpatient and inpatient pediatric IR E&M services.

Android application for determining surgical variables in brain-tumor resection procedures

PubMed Central

Vijayan, Rohan C.; Thompson, Reid C.; Chambless, Lola B.; Morone, Peter J.; He, Le; Clements, Logan W.; Griesenauer, Rebekah H.; Kang, Hakmook; Miga, Michael I.

2017-01-01

Abstract. The fidelity of image-guided neurosurgical procedures is often compromised due to the mechanical deformations that occur during surgery. In recent work, a framework was developed to predict the extent of this brain shift in brain-tumor resection procedures. The approach uses preoperatively determined surgical variables to predict brain shift and then subsequently corrects the patient’s preoperative image volume to more closely match the intraoperative state of the patient’s brain. However, a clinical workflow difficulty with the execution of this framework is the preoperative acquisition of surgical variables. To simplify and expedite this process, an Android, Java-based application was developed for tablets to provide neurosurgeons with the ability to manipulate three-dimensional models of the patient’s neuroanatomy and determine an expected head orientation, craniotomy size and location, and trajectory to be taken into the tumor. These variables can then be exported for use as inputs to the biomechanical model associated with the correction framework. A multisurgeon, multicase mock trial was conducted to compare the accuracy of the virtual plan to that of a mock physical surgery. It was concluded that the Android application was an accurate, efficient, and timely method for planning surgical variables. PMID:28331887

Android application for determining surgical variables in brain-tumor resection procedures.

PubMed

Vijayan, Rohan C; Thompson, Reid C; Chambless, Lola B; Morone, Peter J; He, Le; Clements, Logan W; Griesenauer, Rebekah H; Kang, Hakmook; Miga, Michael I

2017-01-01

The fidelity of image-guided neurosurgical procedures is often compromised due to the mechanical deformations that occur during surgery. In recent work, a framework was developed to predict the extent of this brain shift in brain-tumor resection procedures. The approach uses preoperatively determined surgical variables to predict brain shift and then subsequently corrects the patient's preoperative image volume to more closely match the intraoperative state of the patient's brain. However, a clinical workflow difficulty with the execution of this framework is the preoperative acquisition of surgical variables. To simplify and expedite this process, an Android, Java-based application was developed for tablets to provide neurosurgeons with the ability to manipulate three-dimensional models of the patient's neuroanatomy and determine an expected head orientation, craniotomy size and location, and trajectory to be taken into the tumor. These variables can then be exported for use as inputs to the biomechanical model associated with the correction framework. A multisurgeon, multicase mock trial was conducted to compare the accuracy of the virtual plan to that of a mock physical surgery. It was concluded that the Android application was an accurate, efficient, and timely method for planning surgical variables.

The Varied Circumstances Prompting Requests for Emergency Contraception at School-Based Clinics

ERIC Educational Resources Information Center

Sidebottom, Abbey; Harrison, Patricia A.; Amidon, Donna; Finnegan, Katie

2008-01-01

Background: Little is known about the circumstances that prompt teenagers to request emergency contraception (EC). This evaluation was designed to refine the EC clinical protocol and improve pregnancy prevention efforts in high school-based clinics by analyzing information on EC use and subsequent contraception use of EC patients. Methods: Sites…

The Importance of Early Experiences: Clinical, Research, and Policy Perspectives

ERIC Educational Resources Information Center

Zeanah, Charles H.

2009-01-01

The degree to which early adverse experiences exert long term effects on development and how much early adversity may be overcome through subsequent experiences are important mental health questions. The clinical, research and policy perspectives on these questions lead to different answers. From a clinical perspective, change is always possible,…

The Predictive Value of Ultrasound Learning Curves Across Simulated and Clinical Settings.

PubMed

Madsen, Mette E; Nørgaard, Lone N; Tabor, Ann; Konge, Lars; Ringsted, Charlotte; Tolsgaard, Martin G

2017-01-01

The aim of the study was to explore whether learning curves on a virtual-reality (VR) sonographic simulator can be used to predict subsequent learning curves on a physical mannequin and learning curves during clinical training. Twenty midwives completed a simulation-based training program in transvaginal sonography. The training was conducted on a VR simulator as well as on a physical mannequin. A subgroup of 6 participants underwent subsequent clinical training. During each of the 3 steps, the participants' performance was assessed using instruments with established validity evidence, and they advanced to the next level only after attaining predefined levels of performance. The number of repetitions and time needed to achieve predefined performance levels were recorded along with the performance scores in each setting. Finally, the outcomes were correlated across settings. A good correlation was found between time needed to achieve predefined performance levels on the VR simulator and the physical mannequin (Pearson correlation coefficient .78; P < .001). Performance scores on the VR simulator correlated well to the clinical performance scores (Pearson correlation coefficient .81; P = .049). No significant correlations were found between numbers of attempts needed to reach proficiency across the 3 different settings. A post hoc analysis found that the 50% fastest trainees at reaching proficiency during simulation-based training received higher clinical performance scores compared to trainees with scores placing them among the 50% slowest (P = .025). Performances during simulation-based sonography training may predict performance in related tasks and subsequent clinical learning curves. © 2016 by the American Institute of Ultrasound in Medicine.

Clinical assessment is an accurate predictor of which patients will need septoplasty.

PubMed

Sedaghat, Ahmad R; Busaba, Nicolas Y; Cunningham, Michael J; Kieff, David A

2013-01-01

Septoplasty is a frequently performed surgical procedure with the most common indication being nasal airway obstruction. Almost universally, health insurance companies mandate a trial of medical therapy consisting of intranasal corticosteroids prior to performance of septoplasty regardless of clinical assessment. Evidence for this requirement is lacking. We sought to evaluate the initial clinical assessment as a predictor of response to this mandated trial of medical treatment. Retrospective review of prospectively collected data on 137 consecutive patients who presented with symptoms of nasal obstruction and a deviated nasal septum on physical examination. Patients were placed into one of three cohorts based on prediction of 1) failure of medical therapy with subsequent septoplasty, 2) success of medical therapy without subsequent septoplasty, or 3) unable to make a prediction. Patients from each cohort were assessed for subsequent response to medical therapy and ultimate need for septoplasty. Overall clinical assessment had a sensitivity of 86.9%, specificity of 91.8%, positive predictive value of 93.6%, and negative predictive value of 96.4% for detecting/predicting need for septoplasty. The accuracy of the overall clinical assessment is considerably better than severe deviation at any one septal anatomical site. Of patients whose response to medical therapy could not be predicted, 61.3% failed medical therapy and needed surgery; this is statistically equivalent to a 50/50 distribution between either needing septoplasty or not. Clinical assessment at initial presentation of patients with nasal obstruction and deviated septum is highly accurate in predicting which patients will need septoplasty. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

A 6-year longitudinal study of predictors for suicide attempts in major depressive disorder.

PubMed

Eikelenboom, Merijn; Beekman, Aartjan T F; Penninx, Brenda W J H; Smit, Johannes H

2018-06-13

Major depressive disorder (MDD), represent a major source of risk for suicidality. However, knowledge about risk factors for future suicide attempts (SAs) within MDD is limited. The present longitudinal study examined a wide range of putative non-clinical risk factors (demographic, social, lifestyle, personality) and clinical risk factors (depressive and suicidal indicators) for future SAs among persons with MDD. Furthermore, we examined the relationship between a number of significant predictors and the incidence of a future SA. Data are from 1713 persons (18-65 years) with a lifetime MDD at the baseline measurement of the Netherlands Study of Depression and Anxiety who were subsequently followed up 2, 4 and 6 years. SAs were assessed in the face-to-face measurements. Cox proportional hazard regression analyses were used to examine a wide range of possible non-clinical and clinical predictors for subsequent SAs during 6-year follow-up. Over a period of 6 years, 3.4% of the respondents attempted suicide. Younger age, lower education, unemployment, insomnia, antidepressant use, a previous SA and current suicidal thoughts independently predicted a future SA. The number of significant risk factors (ranging from 0 to 7) linearly predicted the incidence of future SAs: in those with 0 predictors the SA incidence was 0%, which increased to 32% incidence in those with 6+ predictors. Of the non-clinical factors, particularly socio-economic factors predicted a SA independently. Furthermore, preexisting suicidal ideation and insomnia appear to be important clinical risk factors for subsequent SA that are open to preventative intervention.

Electromechanical wave imaging for noninvasive mapping of the 3D electrical activation sequence in canines and humans in vivo

PubMed Central

Konofagou, Elisa E.; Provost, Jean

2014-01-01

Cardiovascular diseases rank as America’s primary killer, claiming the lives of over 41% of more than 2.4 million Americans. One of the main reasons for this high death toll is the severe lack of effective imaging techniques for screening, early detection and localization of an abnormality detected on the electrocardiogram (ECG). The two most widely used imaging techniques in the clinic are CT angiography and echocardiography with limitations in speed of application and reliability, respectively. It has been established that the mechanical and electrical properties of the myocardium change dramatically as a result of ischemia, infarction or arrhythmia; both at their onset and after survival. Despite these findings, no imaging technique currently exists that is routinely used in the clinic and can provide reliable, non-invasive, quantitative mapping of the regional, mechanical and electrical function of the myocardium. Electromechanical Wave Imaging (EWI) is an ultrasound-based technique that utilizes the electromechanical coupling and its associated resulting strain to infer to the underlying electrical function of the myocardium. The methodology of EWI is first described and its fundamental performance is presented. Subsequent in vivo canine and human applications are provided that demonstrate the applicability of Electromechanical Wave Imaging in differentiating between sinus rhythm and induced pacing schemes as well as mapping arrhythmias. Preliminary validation with catheter mapping is also provided and transthoracic electromechanical mapping in all four chambers of the human heart is also presented demonstrating the potential of this novel methodology to noninvasively infer to both the normal and pathological electrical conduction of the heart. PMID:22284425

Sentinel Lymph Node Detection Using Carbon Nanoparticles in Patients with Early Breast Cancer

PubMed Central

Lu, Jianping; Zeng, Yi; Chen, Xia; Yan, Jun

2015-01-01

Purpose Carbon nanoparticles have a strong affinity for the lymphatic system. The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy using carbon nanoparticles in early breast cancer and to optimize the application procedure. Methods Firstly, we performed a pilot study to demonstrate the optimized condition using carbon nanoparticles for sentinel lymph nodes (SLNs) detection by investigating 36 clinically node negative breast cancer patients. In subsequent prospective study, 83 patients with clinically node negative breast cancer were included to evaluate SLNs using carbon nanoparticles. Another 83 SLNs were detected by using blue dye. SLNs detection parameters were compared between the methods. All patients irrespective of the SLNs status underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. Results In pilot study, a 1 ml carbon nanoparticles suspension used 10–15min before surgery was associated with the best detection rate. In subsequent prospective study, with carbon nanoparticles, the identification rate, accuracy, false negative rate was 100%, 96.4%, 11.1%, respectively. The identification rate and accuracy were 88% and 95.5% with 15.8% of false negative rate using blue dye technique. The use of carbon nanoparticles suspension showed significantly superior results in identification rate (p = 0.001) and reduced false-negative results compared with blue dye technique. Conclusion Our study demonstrated feasibility and accuracy of using carbon nanoparticles for SLNs mapping in breast cancer patients. Carbon nanoparticles are useful in SLNs detection in institutions without access to radioisotope. PMID:26296136

New technologies and surgical innovation: five years of a local health technology assessment program in a surgical department.

PubMed

Poulin, Paule; Austen, Lea; Kortbeek, John B; Lafrenière, René

2012-06-01

There is pressure for surgical departments to introduce new and innovative health technologies in an evidence-based manner while ensuring that they are safe and effective and can be managed with available resources. A local health technology assessment (HTA) program was developed to systematically integrate research evidence with local operational management information and to make recommendations for subsequent decision by the departmental executive committee about whether and under what conditions the technology will be used. The authors present a retrospective analysis of the outcomes of this program as used by the Department of Surgery & Surgical Services in the Calgary Health Region over a 5-year period from December 2005 to December 2010. Of the 68 technologies requested, 15 applications were incomplete and dropped, 12 were approved, 3 were approved for a single case on an urgent/emergent basis, 21 were approved for "clinical audit" for a restricted number of cases with outcomes review, 14 were approved for research use only, and 3 were referred to additional review bodies. Subsequent outcome reports resulted in at least 5 technologies being dropped for failure to perform. Decisions based on local HTA program recommendations were rarely "yes" or "no." Rather, many technologies were given restricted approval with full approval contingent on satisfying certain conditions such as clinical outcomes review, training protocol development, or funding. Thus, innovation could be supported while ensuring safety and effectiveness. This local HTA program can be adapted to a variety of settings and can help bridge the gap between evidence and practice.

Does nitrogen fertilizer application rate to corn affect nitrous oxide emissions from the rotated soybean crop?

PubMed

Iqbal, Javed; Mitchell, David C; Barker, Daniel W; Miguez, Fernando; Sawyer, John E; Pantoja, Jose; Castellano, Michael J

2015-05-01

Little information exists on the potential for N fertilizer application to corn ( L.) to affect NO emissions during subsequent unfertilized crops in a rotation. To determine if N fertilizer application to corn affects NO emissions during subsequent crops in rotation, we measured NO emissions for 3 yr (2011-2013) in an Iowa, corn-soybean [ (L.) Merr.] rotation with three N fertilizer rates applied to corn (0 kg N ha, the recommended rate of 135 kg N ha, and a high rate of 225 kg N ha); soybean received no N fertilizer. We further investigated the potential for a winter cereal rye ( L.) cover crop to interact with N fertilizer rate to affect NO emissions from both crops. The cover crop did not consistently affect NO emissions. Across all years and irrespective of cover crop, N fertilizer application above the recommended rate resulted in a 16% increase in mean NO flux rate during the corn phase of the rotation. In 2 of the 3 yr, N fertilizer application to corn (0-225 kg N ha) did not affect mean NO flux rates from the subsequent unfertilized soybean crop. However, in 1 yr after a drought, mean NO flux rates from the soybean crops that received 135 and 225 kg N ha N application in the corn year were 35 and 70% higher than those from the soybean crop that received no N application in the corn year. Our results are consistent with previous studies demonstrating that cover crop effects on NO emissions are not easily generalizable. When N fertilizer affects NO emissions during a subsequent unfertilized crop, it will be important to determine if total fertilizer-induced NO emissions are altered or only spread across a greater period of time. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Esophageal perforation due to blunt chest trauma: Difficult diagnosis because of coexisting severe disturbance of consciousness.

PubMed

Mezuki, Satomi; Shono, Yuji; Akahoshi, Tomohiko; Hisanaga, Kana; Saeki, Hiroshi; Nakashima, Yuichiro; Momii, Kenta; Maki, Jun; Tokuda, Kentaro; Maehara, Yoshihiko

2017-11-01

Esophageal perforation due to blunt trauma is a rare clinical condition, and the diagnosis is often difficult because patients have few specific symptoms. Delayed diagnosis may result in a fatal clinical course due to mediastinitis and subsequent sepsis. In this article, we describe a 26-year-old man with esophageal perforation due to blunt chest trauma resulting from a motor vehicle accident. Because a severe disturbance of consciousness masked the patient's trauma-induced thoracic symptoms, we required 11h to diagnose the esophageal perforation. Therefore, the patient developed septic shock due to mediastinitis. However, his subsequent clinical course was good because of prompt combined therapy involving surgical repair and medical treatment after the diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Ratio of urine and blood urea nitrogen concentration predicts the response of tolvaptan in congestive heart failure.

PubMed

Shimizu, Keisuke; Doi, Kent; Imamura, Teruhiko; Noiri, Eisei; Yahagi, Naoki; Nangaku, Masaomi; Kinugawa, Koichiro

2015-06-01

This study was conducted to evaluate the performance of the ratio of urine and blood urea nitrogen concentration (UUN/BUN) as a new predictive factor for the response of an arginine vasopressin receptor 2 antagonist tolvaptan (TLV) in decompensated heart failure patients. This study enrolled 70 decompensated heart failure patients who were administered TLV at University of Tokyo Hospital. We collected the data of clinical parameters including UUN/BUN before administering TLV. Two different outcomes were defined as follows: having over 300 mL increase in urine volume on the first day (immediate urine output response) and having any decrease in body weight within one week after starting TLV treatment (subsequent clinical response). Among the 70 enrolled patients, 37 patients (52.9%) showed immediate urine output response; 51 patients (72.9%) showed a subsequent clinical response of body weight decrease. Receiver operating characteristics (ROC) analysis showed good prediction by UUN/BUN for the immediate response (AUC-ROC 0.86 [0.75-0.93]) and a significantly better prediction by UUN/BUN for the subsequent clinical response compared with urinary osmolality (AUC-ROC 0.78 [0.63-0.88] vs. 0.68 [0.52-0.80], P < 0.05). We demonstrated that a clinical parameter of UUN/BUN can predict the response of TLV even when measured before TLV administration. UUN/BUN might enable identification of good responders for this new drug. © 2015 Asian Pacific Society of Nephrology.

[Psychology and nutrition in the ontogenetic development in the infant-adolescence years].

PubMed

Fuillerat Alfonso, R

2004-01-01

The relationship between the psychic development and the nutritional condition from the fetal stage up to the teenage years is the innermost objective of this study. The importance of eating and having an adequate diet during the pregnancy period, the training of the future mother to breast feed in the first months of the baby's life and the subsequent application of the ablactación process and its relation with psychomotor development and the personality progression in the different stages of the psychological, physiological and social development of the infant-adolescent period. The results shown were obtained from various studies carried out in the Nutritional Clinical Service. They are related to the reinduction of breast feeding in children less than 4 months of age with protein energetic malnutrition, as well as other stages of the infant-juvenile obese and other chronic and genetic diseases related to the nourishment and nutrition (diabetes, fenilcetonuria, hiperamonemia, homocistinuria y fibrosis quística), in which the close relationship betweeen the Psychology, and the Nutrition stands, all through the Psychotherapeutic and educational treatments and based on the application of the clinic psychology in the prevention, promotion and treatment of the nutritional alterations and other chronic and genetic diseases related to nourishment and malnutrition. Aspects related to the psychological and social characterizations as well as the personality evolution of these patients and their relatives environment are established.

Platelet growth factors from allogeneic platelet-rich plasma for clinical improvement in split-thickness skin graft.

PubMed

Sonker, Atul; Dubey, Anju; Bhatnagar, Ankur; Chaudhary, Rajendra

2015-01-01

Platelets are a source of numerous growth factors which facilitate repair and healing. Thus platelet rich plasma has been increasingly used as a treatment modality in the field of reconstructive surgeries for wound healing. This preliminary study was carried out to explore whether platelet growth factors from platelet rich plasma could be used for enhancement of split thickness skin graft survival. Twenty patients (13 males and 7 females) requiring split thickness skin graft for various clinical reasons were enrolled in the study. Platelet rich plasma was collected by apheresis and frozen at -80° C. It was thawed at room temperature immediately before its intended application. PRP was applied only on one half of the wound, while another half served as control. Patient was followed for 6 weeks. The effect was assessed at first dressing in terms of graft uptake and subsequently as time taken for complete healing. There was 100% uptake of the graft in the area where platelet rich plasma was applied. In the control area, there was complete graft loss in 4 cases, partial loss in 7 cases and complete uptake in 9 cases. This study demonstrated promising results on application of PRP to split thickness skin grafts. Further randomized studies with greater sample size may be undertaken to establish platelet rich plasma as a validated treatment modality.

Neuron-Type-Specific Utility in a Brain-Machine Interface: a Pilot Study.

PubMed

Garcia-Garcia, Martha G; Bergquist, Austin J; Vargas-Perez, Hector; Nagai, Mary K; Zariffa, Jose; Marquez-Chin, Cesar; Popovic, Milos R

2017-11-01

Firing rates of single cortical neurons can be volitionally modulated through biofeedback (i.e. operant conditioning), and this information can be transformed to control external devices (i.e. brain-machine interfaces; BMIs). However, not all neurons respond to operant conditioning in BMI implementation. Establishing criteria that predict neuron utility will assist translation of BMI research to clinical applications. Single cortical neurons (n=7) were recorded extracellularly from primary motor cortex of a Long-Evans rat. Recordings were incorporated into a BMI involving up-regulation of firing rate to control the brightness of a light-emitting-diode and subsequent reward. Neurons were classified as 'fast-spiking', 'bursting' or 'regular-spiking' according to waveform-width and intrinsic firing patterns. Fast-spiking and bursting neurons were found to up-regulate firing rate by a factor of 2.43±1.16, demonstrating high utility, while regular-spiking neurons decreased firing rates on average by a factor of 0.73±0.23, demonstrating low utility. The ability to select neurons with high utility will be important to minimize training times and maximize information yield in future clinical BMI applications. The highly contrasting utility observed between fast-spiking and bursting neurons versus regular-spiking neurons allows for the hypothesis to be advanced that intrinsic electrophysiological properties may be useful criteria that predict neuron utility in BMI implementation.

Assessing the Relationship between Vitamin D3 and Stratum Corneum Hydration for the Treatment of Xerotic Skin

PubMed Central

Russell, Meghan

2012-01-01

Vitamin D3 has been called the “sunshine” vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D3 is linked to many health benefits, however serum levels of vitamin D3 have been decreasing over the last few decades and the lower levels of vitamin D3 may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D3) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D3 (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D3. PMID:23112909

Assessing the relationship between vitamin D3 and stratum corneum hydration for the treatment of xerotic skin.

PubMed

Russell, Meghan

2012-09-01

Vitamin D(3) has been called the "sunshine" vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many health benefits, however serum levels of vitamin D(3) have been decreasing over the last few decades and the lower levels of vitamin D(3) may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D(3)) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3).

Biology and Biomarkers for Wound Healing.

PubMed

Lindley, Linsey E; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-09-01

As the population grows older, the incidence and prevalence of conditions that lead to a predisposition for poor wound healing also increase. Ultimately, this increase in nonhealing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has and will continue to be the leading pathway to the discovery of therapeutic targets, as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of nonhealing patients for whom biomarker-guided approaches may aid in healing. A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Currently, biomarkers are being identified using biomaterials sourced locally from human wounds and/or systemically using high-throughput "omics" modalities (genomic, proteomic, lipidomic, and metabolomic analysis). In this review, we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum, including those measured in tissue specimens, for example, β-catenin and c-myc, wound fluid, matrix metalloproteinases and interleukins, swabs, wound microbiota, and serum, for example, procalcitonin and matrix metalloproteinases. Identification of numerous potential biomarkers using different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity and consistent implementation of these biomarkers, as well as an emphasis on efficacious follow-up therapeutics, is necessary for transition of this technology to clinically feasible point-of-care applications.

Surface-Enhanced Raman Scattering (SERS) in Microbiology: Illumination and Enhancement of the Microbial World.

PubMed

Chisanga, Malama; Muhamadali, Howbeer; Ellis, David I; Goodacre, Royston

2018-01-01

The microbial world forms a huge family of organisms that exhibit the greatest phylogenetic diversity on Earth and thus colonize virtually our entire planet. Due to this diversity and subsequent complex interactions, the vast majority of microorganisms are involved in innumerable natural bioprocesses and contribute an absolutely vital role toward the maintenance of life on Earth, whilst a small minority cause various infectious diseases. The ever-increasing demand for environmental monitoring, sustainable ecosystems, food security, and improved healthcare systems drives the continuous search for inexpensive but reproducible, automated and portable techniques for detection of microbial isolates and understanding their interactions for clinical, environmental, and industrial applications and benefits. Surface-enhanced Raman scattering (SERS) is attracting significant attention for the accurate identification, discrimination and characterization and functional assessment of microbial cells at the single cell level. In this review, we briefly discuss the technological advances in Raman and Fourier transform infrared (FT-IR) instrumentation and their application for the analysis of clinically and industrially relevant microorganisms, biofilms, and biological warfare agents. In addition, we summarize the current trends and future prospects of integrating Raman/SERS-isotopic labeling and cell sorting technologies in parallel, to link genotype-to-phenotype in order to define community function of unculturable microbial cells in mixed microbial communities which possess admirable traits such as detoxification of pollutants and recycling of essential metals.

Cascade Signal Amplification Based on Copper Nanoparticle-Reported Rolling Circle Amplification for Ultrasensitive Electrochemical Detection of the Prostate Cancer Biomarker.

PubMed

Zhu, Ye; Wang, Huijuan; Wang, Lin; Zhu, Jing; Jiang, Wei

2016-02-03

An ultrasensitive and highly selective electrochemical assay was first attempted by combining the rolling circle amplification (RCA) reaction with poly(thymine)-templated copper nanoparticles (CuNPs) for cascade signal amplification. As proof of concept, prostate specific antigen (PSA) was selected as a model target. Using a gold nanoparticle (AuNP) as a carrier, we synthesized the primer-AuNP-aptamer bioconjugate for signal amplification by increasing the primer/aptamer ratio. The specific construction of primer-AuNP-aptamer/PSA/anti-PSA sandwich structure triggered the effective RCA reaction, in which thousands of tandem poly(thymine) repeats were generated and directly served as the specific templates for the subsequent CuNP formation. The signal readout was easily achieved by dissolving the RCA product-templated CuNPs and detecting the released copper ions with differential pulse stripping voltammetry. Because of the designed cascade signal amplification strategy, the newly developed method achieved a linear range of 0.05-500 fg/mL, with a remarkable detection limit of 0.020 ± 0.001 fg/mL PSA. Finally, the feasibility of the developed method for practical application was investigated by analyzing PSA in the real clinical human serum samples. The ultrasensitivity, specificity, convenience, and capability for analyzing the clinical samples demonstrate that this method has great potential for practical disease diagnosis applications.

Transgender youth: current concepts

PubMed Central

2016-01-01

In many countries throughout the world, increasing numbers of gender nonconforming/transgender youth are seeking medical services to enable the development of physical characteristics consistent with their experienced gender. Such medical services include use of agents to block endogenous puberty at Tanner stage II with subsequent use of cross-sex hormones, and are based on longitudinal studies demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and continue to meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. This review addresses terms and definitions applicable to gender nonconforming youth, studies that shed light on the biologic determinants of gender identity, current clinical practice guidelines for transgender youth, challenges to optimal care, and priorities for research. PMID:28164070

Bayesian statistics in medicine: a 25 year review.

PubMed

Ashby, Deborah

2006-11-15

This review examines the state of Bayesian thinking as Statistics in Medicine was launched in 1982, reflecting particularly on its applicability and uses in medical research. It then looks at each subsequent five-year epoch, with a focus on papers appearing in Statistics in Medicine, putting these in the context of major developments in Bayesian thinking and computation with reference to important books, landmark meetings and seminal papers. It charts the growth of Bayesian statistics as it is applied to medicine and makes predictions for the future. From sparse beginnings, where Bayesian statistics was barely mentioned, Bayesian statistics has now permeated all the major areas of medical statistics, including clinical trials, epidemiology, meta-analyses and evidence synthesis, spatial modelling, longitudinal modelling, survival modelling, molecular genetics and decision-making in respect of new technologies.

Ocular Applications of Dipyridamole: A Review of Indications and Routes of Administration

PubMed Central

Isakov, Itzhak; Wlassoff, Wjatschesslaw; Ingram, April; Barishak, Y. Robert

2016-01-01

Abstract Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration. PMID:26696547

Report from the 2013 meeting of the International Compression Club on advances and challenges of compression therapy.

PubMed

Delos Reyes, Arthur P; Partsch, Hugo; Mosti, Giovanni; Obi, Andrea; Lurie, Fedor

2014-10-01

The International Compression Club, a collaboration of medical experts and industry representatives, was founded in 2005 to develop consensus reports and recommendations regarding the use of compression therapy in the treatment of acute and chronic vascular disease. During the recent meeting of the International Compression Club, member presentations were focused on the clinical application of intermittent pneumatic compression in different disease scenarios as well as on the use of inelastic and short stretch compression therapy. In addition, several new compression devices and systems were introduced by industry representatives. This article summarizes the presentations and subsequent discussions and provides a description of the new compression therapies presented. Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

PubMed Central

2012-01-01

Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

Mobile phones support adherence and retention of indigenous participants in a randomised controlled trial: strategies and lessons learnt.

PubMed

McCallum, Gabrielle B; Versteegh, Lesley A; Morris, Peter S; Mckay, Clare C; Jacobsen, Nerida J; White, Andrew V; D'Antoine, Heather A; Chang, Anne B

2014-06-18

Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children. This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21. Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21. In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes. ACTRN12608000150347 (RCT component).

Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

PubMed

Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

2013-01-01

Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

PS1-41: Just Add Data: Implementing an Event-Based Data Model for Clinical Trial Tracking

PubMed Central

Fuller, Sharon; Carrell, David; Pardee, Roy

2012-01-01

Background/Aims Clinical research trials often have similar fundamental tracking needs, despite being quite variable in their specific logic and activities. A model tracking database that can be quickly adapted by a variety of studies has the potential to achieve significant efficiencies in database development and maintenance. Methods Over the course of several different clinical trials, we have developed a database model that is highly adaptable to a variety of projects. Rather than hard-coding each specific event that might occur in a trial, along with its logical consequences, this model considers each event and its parameters to be a data record in its own right. Each event may have related variables (metadata) describing its prerequisites, subsequent events due, associated mailings, or events that it overrides. The metadata for each event is stored in the same record with the event name. When changes are made to the study protocol, no structural changes to the database are needed. One has only to add or edit events and their metadata. Changes in the event metadata automatically determine any related logic changes. In addition to streamlining application code, this model simplifies communication between the programmer and other team members. Database requirements can be phrased as changes to the underlying data, rather than to the application code. The project team can review a single report of events and metadata and easily see where changes might be needed. In addition to benefitting from streamlined code, the front end database application can also implement useful standard features such as automated mail merges and to do lists. Results The event-based data model has proven itself to be robust, adaptable and user-friendly in a variety of study contexts. We have chosen to implement it as a SQL Server back end and distributed Access front end. Interested readers may request a copy of the Access front end and scripts for creating the back end database. Discussion An event-based database with a consistent, robust set of features has the potential to significantly reduce development time and maintenance expense for clinical trial tracking databases.

Calibration of EMG to force for knee muscles is applicable with submaximal voluntary contractions.

PubMed

Doorenbosch, Caroline A M; Joosten, Annemiek; Harlaar, Jaap

2005-08-01

In this study, the influence of using submaximal isokinetic contractions about the knee compared to maximal voluntary contractions as input to obtain the calibration of an EMG-force model for knee muscles is investigated. Isokinetic knee flexion and extension contractions were performed by healthy subjects at five different velocities and at three contraction levels (100%, 75% and 50% of MVC). Joint angle, angular velocity, joint moment and surface EMG of five knee muscles were recorded. Individual calibration values were calculated according to [C.A.M. Doorenbosch, J. Harlaar, A clinically applicable EMG-force model to quantify active stabilization of the knee after a lesion of the anterior cruciate ligament, Clinical Biomechanics 18 (2003) 142-149] for each contraction level. First, the output of the model, calibrated with the 100% MVC was compared to the actually exerted net knee moment at the dynamometer. Normalized root mean square errors were calculated [A.L. Hof, C.A.N. Pronk, J.A. van Best, Comparison between EMG to force processing and kinetic analysis for the calf muscle moment in walking and stepping, Journal of Biomechanics 20 (1987) 167-187] to compare the estimated moments with the actually exerted moments. Mean RMSD errors ranged from 0.06 to 0.21 for extension and from 0.12 to 0.29 for flexion at the 100% trials. Subsequently, the calibration results of the 50% and 75% MVC calibration procedures were used. A standard signal, representing a random EMG level was used as input in the EMG force model, to compare the three models. Paired samples t-tests between the 100% MVC and the 75% MVC and 50% MVC, respectively, showed no significant differences (p>0.05). The application of submaximal contractions of larger than 50% MVC is suitable to calibrate a simple EMG to force model for knee extension and flexion. This means that in clinical practice, the EMG to force model can be applied by patients who cannot exert maximal force.

The Influence of International Service-Learning on Transcultural Self-Efficacy in Baccalaureate Nursing Graduates and Their Subsequent Practice

ERIC Educational Resources Information Center

Amerson, Roxanne

2012-01-01

The purpose of this study was to explain how participation in an international service-learning project during a community health course influenced transcultural self-efficacy of baccalaureate nursing graduates following graduation and their subsequent clinical practice. A qualitative, explanatory case study was used to conduct telephone…

Effectiveness of early cardiology undergraduate learning using simulation on retention, application of learning and level of confidence during clinical clerkships

PubMed Central

Lin, Weiqin; Lee, Glenn K; Loh, Joshua P; Tay, Edgar L; Sia, Winnie; Lau, Tang-Ching; Hooi, Shing-Chuan; Poh, Kian-Keong

2015-01-01

INTRODUCTION This study aimed to assess the effectiveness of the use of a cardiopulmonary patient simulator in the teaching of second-year medical students. Effectiveness was measured in terms of the extent of knowledge retention and students’ ability to apply the skills learned in subsequent real-life patient contact. METHODS In this study, ten third-year medical students who had previously undergone simulator training as part of their second-year curriculum underwent an objective structured clinical examination (OSCE) and a multiple-choice question (MCQ) test to assess their ability to apply the knowledge gained during the simulator training when dealing with real patients. The performance of this group of students was compared with that of a group of ten fourth-year medical students who did not undergo simulation training. RESULTS Although the third-year medical students performed well in the OSCE, they were outperformed by the group of fourth-year medical students, who had an extra year of clinical exposure. The MCQ scores of the two groups of students were similar. Post-simulation training survey revealed that students were generally in favour of incorporating cardiopulmonary simulator training in the preclinical curriculum. CONCLUSION Cardiopulmonary simulator training is a useful tool for the education of preclinical medical students. It aids the translation of preclinical knowledge into real-life clinical skills. PMID:25715855

Dimethyl sulfoxide could be a useful probe to evaluate unusual skin angioneurotic reaction and epidermal permeability.

PubMed

Chen, Shuang Y; Wang, Xue M; Liu, Yan Q; Gao, Yan R; Liu, Xiao P; Li, Shu Y; Dong, Ya Q

2014-03-01

Dimethyl sulfoxide (DMSO) has been suggested as a traditional chemical probe for assessing skin susceptibility and barrier function. The purpose of this study was to determine the role of DMSO test for the evaluation of unusual skin angioneurotic reaction and epidermal permeability. Thirty healthy volunteers were exposed to 98% DMSO on the flexor forearm skin for three exposure durations (5 min, 10 min and 15 min). Clinical visual score and biological physical parameters were obtained. The volunteers were divided into two groups according to the clinical visual scoring. The skin parameters were subsequently analyzed. There was a significant correlation between clinical visual score and biological physical parameters. The skin color parameters (a*, oxyhemoglobin, erythema and melanin index) and blood flow values were significant between two groups regardless of duration of DMSO exposure, and a significant difference between density values could also be detected if we regrouped the volunteers according to the sting-producing score. Our results also suggested there was no correlation between questionnaire score and clinical visual score or other parameters. Application of 98% DMSO for 10 min combined with a* (at 30 min) and blood flow (at 10 min) values could help us to identify persons with a hyper-angionerotic reaction to chemical stimulus. The penetrative activity of DMSO correlated with the thickness of the individual's skin.

Evaluation of a Program by Assessing Students' Performance at the Beginning of the Next Course

ERIC Educational Resources Information Center

And Others; Petzel, Robert A.

1978-01-01

A method of evaluating a first-year introduction to clinical medicine (ICM) course is described in which assessment of student achievement of the course goals is made by subsequent clinical tutors. Tutors drawn from several clinical departments are urged to maximize students' opportunities to practice taking complete histories and physical…

Understanding the Benefits and Limitations of Magnetic Nanoparticle Heating for Improved Applications in Cancer Hyperthermia and Biomaterial Cryopreservation

NASA Astrophysics Data System (ADS)

Etheridge, Michael L.

The current work focused on the ability of magnetic nanoparticles to produce heat in the presence of an applied alternating magnetic field. Magnetic nanoparticle hyperthermia applications utilize this behavior to treat cancer and this approach has received clinical approval in the European Union, but significant developments are necessary for this technology to have a chance for wider-spread acceptance. Here then we begin by investigating some of the important limitations of the current technology. By characterizing the ability of superparamagnetic and ferromagnetic nanoparticles to heat under a range of applied fields, we are able to determine the optimal field settings for clinical application and make recommendations on the highest impact strategies to increase heating. In addition, we apply these experimentally determined limits to heating in a series of heat transfer models, to demonstrate the therapeutic impact of nanoparticle concentration, target volume, and delivery strategy. Next, we attempt to address one of the key questions facing the field- what is the impact of biological aggregation on heating? Controlled aggregate populations are produced and characterized in ionic and protein solutions and their heating is compared with nanoparticles incubated in cellular suspensions. Through this investigation we are able to demonstrate that aggregation is responsible for up to a 50% decrease in heating. However, more importantly, we are able to demonstrate that the observed reductions in heating correlate with reductions in longitudinal relaxation (T1) measured by sweep imaging with Fourier transformation (SWIFT) magnetic resonance imaging (MRI), providing a potential platform to account for these aggregation effects and directly predict heating in a clinical setting. Finally, we present a new application for magnetic nanoparticle heating, in the thawing of cryopreserved biomaterials. A number of groups have demonstrated the ability to rapidly cool and preserve tissues in the vitreous state, but crystallization and cracking failures occur upon the subsequent thaw. Magnetic nanoparticles offer a potential solution to these issues, through their ability to provide rapid, uniform heating, and we illustrate this through heating in several cryoprotectant solutions and by modeling the effects of heating at the bulk and micro-scales.

Emergency thoracic ultrasound and clinical risk management

PubMed Central

Interrigi, Maria Concetta; Trovato, Francesca M; Catalano, Daniela; Trovato, Guglielmo M

2017-01-01

Purpose Thoracic ultrasound (TUS) has been proposed as an easy-option replacement for chest X-ray (CXR) in emergency diagnosis of pneumonia, pleural effusion, and pneumothorax. We investigated CXR unforeseen diagnosis, subsequently investigated by TUS, considering its usefulness in clinical risk assessment and management and also assessing the sustainability of telementoring. Patients and methods This observational report includes a period of 6 months with proactive concurrent adjunctive TUS diagnosis telementoring, which was done using freely available smartphone applications for transfer of images and movies. Results Three hundred and seventy emergency TUS scans (excluding trauma patients) were performed and telementored. In 310 cases, no significant chest pathology was detected either by CXR, TUS, or the subsequent work-up; in 24 patients, there was full concordance between TUS and CXR (ten isolated pleural effusion; eleven pleural effusion with lung consolidations; and three lung consolidation without pleural effusion); in ten patients with lung consolidations, abnormalities identified by CXR were not detected by TUS. In 26 patients, only TUS diagnosis criteria of disease were present: in 19 patients, CXR was not diagnostic, ie, substantially negative, but TUS detected these conditions correctly, and these were later confirmed by computed tomography (CT). In seven patients, even if chest disease was identified by CXR, such diagnoses were significantly modified by ultrasound, and CT confirmed that TUS was more appropriate. The overall respective individual performances of CXR and TUS for the diagnosis of a pleural–pulmonary disease in emergency are good, with accuracy >95%. Conclusion About 20% of pneumonia cases were detectable only by CXR and 20% only by TUS and not by CXR; ie, about 40% of patients may have been misdiagnosed if, by chance, only one of the two tools had been used. The concurrent use of TUS and CXR increases the overall sensitivity and specificity. The contribution of expert telementoring and final reappraisal is a valuable and sustainable element for emergency physicians’ training and performance, contributing reasonably to mitigation of clinical risks. PMID:28223817

Fiat Chrysler Application for Alternative Methodology for Off-Cycle Technology Credits: High Efficiency Alternators

EPA Pesticide Factsheets

FCA Group LLC request to the EPA regarding greenhouse gas, off-cycle CO2 credits for High Efficiency Alternators used on 2009 and subsequent model year vehicles and off-cycle fuel consumption credits for 2017 and subsequent model year vehicles.

The Model Life-cycle: Training Module

EPA Pesticide Factsheets

Model Life-Cycle includes identification of problems & the subsequent development, evaluation, & application of the model. Objectives: define ‘model life-cycle’, explore stages of model life-cycle, & strategies for development, evaluation, & applications.

Clinical Trials: Understanding and Perceptions of Female Chinese-American Cancer Patients

PubMed Central

Tu, Shin-Ping; Chen, Hueifang; Chen, Anthony; Lim, Jeanette; May, Suepattra; Drescher, Charles

2006-01-01

Under-representation of minority and female participants prompted the U.S. legislature to mandate the inclusion of women and minorities in federally funded research. Recruitment of minorities to participate in clinical trials continues to be challenging. Although Asian Americans constitute one of the major minority groups in the U.S., published literature contains sparse data concerning the participation of Asian Americans in cancer clinical trials. The authors completed qualitative, semistructured interviews with 34 participants: Chinese-American female cancer patients ages 20–85 years or their family members. Interviews were conducted in Cantonese, Mandarin, or English and were audiotaped. Chinese interviews were translated into English, and all interviews were transcribed subsequently into English. A team of five coders individually reviewed then met to discuss the English transcripts. The authors used the constant comparative technique throughout the entire coding process as part of the analysis. Among participants, 62% lacked any knowledge of clinical trials, and many expressed negative attitudes toward clinical trials. Barriers to participation included inadequate resources, language issues, and a lack of financial and social support. Facilitating factors included recommendations by a trusted oncologist or another trusted individual and information in the appropriate language. It is noteworthy that family members played an important role in the cancer experience of these participants. To promote participation, there is a need to increase knowledge of clinical trials among Chinese cancer patients. It also is necessary to examine the applicability of current patient-physician communication and interaction models. In addition, decision-making based on Asian philosophies within the context of Euro-American bio-ethics requires further study. PMID:16247796

Research, evidence, and ethics: new technology or grey medicine.

PubMed

Zhai, Haoran; Zhong, Wenzhao; Wu, Yilong

2015-02-01

Major pioneering advances of medicine in history tend to manifest in two directions that seem divergent but actually unified with dialectics: one is the important biological principle revealed by in-depth studies from the clinic to the laboratory based on individual cases; the other is the colonial generality displayed by epidemiologic data from large-scale samples. Although advances predominated, we human beings were paying dearly for it due to serious incidents of endangering ourselves and defects of restrictions of laws and ethics. Subsequently, the Nuremberg Code, Declaration of Helsinki and Belmont Report came into light and constrained human experiments and clinical trials. However, the development of such laws and regulations in China is lagging behind and renders China as a breeding ground for gray medicine. There are three lessons we can learn from painful histories and apply to individualized treatment of lung cancer. Firstly, the abuse of Avastin beyond its indications reflected the similar situation of tyrosine kinase inhibitors in lung cancer due to different molecular types and stages of tumors; secondly, the black market of stem cell therapy in China reminds us how to identify the boundaries of clinical trials and clinical treatment, in similar to the cellular immunotherapy of tumors; thirdly, the theory of Xiao's Reflex Arc emerged us to rethink the level of the validity of clinical evidences, which can provide hints related to video-assisted thoracoscopic surgeries (VATSs). In conclusion, clinical applications of new techniques and treatment regimens should follow three points: identify indications and contraindications clearly, obtain informed consent and permission of patients and supervise effectively according to laws and ethics.

Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

PubMed

Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

2016-05-01

We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury. © 2016 Wiley Periodicals, Inc.

Gastric ulceration subsequent to partial invagination of the stomach in a dog with gastric dilatation-volvulus.

PubMed

Parton, Amanda T; Volk, Susan W; Weisse, Chick

2006-06-15

CASE DESCRIPTION-An 8-year-old castrated male German Shepherd Dog was evaluated because of abdominal distension, retching, and vomiting. CLINICAL FINDINGS-Gastric dilatation-volvulus was suspected on the basis of the dog's signalment, history, clinical signs, and results of clinicopathologic analyses and abdominal radiography. Celiotomy was performed, and gastric dilatation-volvulus was confirmed along with splenomegaly. Gastric invagination was performed over an area of gastric necrosis. The dog was reevaluated 21 days later after an episode of collapse. Findings of physical examination and clinicopathologic analyses were suggestive of internal hemorrhage. Abdominal ultrasonography and subsequent celiotomy revealed severe gastric ulceration at the gastric invagination site, splenic torsion, and a focal splenic infarct. TREATMENT AND OUTCOME-Splenectomy and gastrectomy of the necrotic tissue were performed. The dog was discharged from the hospital, and the owner was instructed to administer gastroprotectants and feed the dog a bland diet. The dog was reported to be healthy 3.25 years after surgery. CLINICAL RELEVANCE-Findings suggest that complications associated with the gastric invagination procedure include severe gastric ulceration that may require subsequent surgery. Prolonged treatment with gastroprotectants following gastric invagination surgery may be necessary to avoid gastric ulceration in dogs.

Total hip arthroplasty of dysplastic hip after previous Chiari pelvic osteotomy.

PubMed

Minoda, Yukihide; Kadowaki, Toru; Kim, Mitsunari

2006-08-01

Many reports have suggested that Chiari pelvic osteotomy would improve the results of acetabular component placement and fixation in subsequent total hip arthroplasty. However, little is known concerning the biomechanical, radiological, and clinical effects of Chiari pelvic osteotomy on subsequent total hip arthroplasty. Ten total hip arthroplasties for developmental dysplasia of the hip after previous Chiari pelvic osteotomy (Chiari group) were compared with 20 total hip arthroplasties for developmental dysplasia of the hip without previous surgery (control group). Preoperative patient demographic data and operative technique were well matched between the groups. The mean duration of follow-up was 3.0 years. Biomechanical, radiological, and clinical evaluations were performed. No acetabular or femoral components exhibited loosening. All patients had good or excellent clinical score according to the Merle d'Aubigne-Postel rating system at the most recent follow-up. Abductor force and joint force were smaller in the Chiari group, although long operative time, more blood loss, and verticalization of joint force were noted in this group. This limited study suggested that Chiari pelvic osteotomy changed the biomechanical features of the hip joint, and that this alteration might have compromised subsequent total hip arthroplasty.

In-vitro and clinical evaluation of transurethral laser-induced prostatectomy (TULIP)

NASA Astrophysics Data System (ADS)

van Swol, Christiaan F. P.; Verdaasdonck, Rudolf M.; Mooibroek, Jaap; Boon, Tom A.

1993-05-01

Transurethral ultrasound-guided laser induced prostatectomy (TULIP) is a recent development in the treatment of benign prostatic hyperplasia. The system is based upon Nd:YAG laser irradiation delivered by a right angled fiber. The dosimetry used in a clinical situation is mostly based upon animal studies. In this study, the light and temperature distribution in the prostate during Nd:YAG laser irradiation were modeled using Monte Carlo and finite differences theory. The results of this model were compared with in vitro experiments. The influence of the different parameters involved, e.g., the scanning speed and the power of the laser beam, were evaluated. Initial results show the temperature distribution and thus the therapeutic effect of the TULIP procedure. Until now 36 patients have been treated successfully. The mean in-hospital time was somewhat shorter than for a TURP treatment while the results were comparable. These treatments, however, show the need for a better understanding of the mechanisms involved. Modeling and subsequent in vitro and in vivo measurements might improve the understanding and safe and successful application of prostate treatment using laser based systems.

Cationic nanoemulsions as nucleic acids delivery systems.

PubMed

Teixeira, Helder Ferreira; Bruxel, Fernanda; Fraga, Michelle; Schuh, Roselena Silvestri; Zorzi, Giovanni Konat; Matte, Ursula; Fattal, Elias

2017-12-20

Since the first clinical studies, knowledge in the field of gene therapy has advanced significantly, and these advances led to the development and subsequent approval of the first gene medicines. Although viral vectors-based products offer efficient gene expression, problems related to their safety and immune response have limited their clinical use. Thus, design and optimization of nonviral vectors is presented as a promising strategy in this scenario. Nonviral systems are nanotechnology-based products composed of polymers or lipids, which are usually biodegradable and biocompatible. Cationic liposomes are the most studied nonviral carriers and knowledge about these systems has greatly evolved, especially in understanding the role of phospholipids and cationic lipids. However, the search for efficient delivery systems aiming at gene therapy remains a challenge. In this context, cationic nanoemulsions have proved to be an interesting approach, as their ability to protect and efficiently deliver nucleic acids for diverse therapeutic applications has been demonstrated. This review focused on cationic nanoemulsions designed for gene therapy, providing an overview on their composition, physicochemical properties, and their efficacy on biological response in vitro and in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells.

PubMed

Takebe, Takanori; Sekine, Keisuke; Kimura, Masaki; Yoshizawa, Emi; Ayano, Satoru; Koido, Masaru; Funayama, Shizuka; Nakanishi, Noriko; Hisai, Tomoko; Kobayashi, Tatsuya; Kasai, Toshiharu; Kitada, Rina; Mori, Akira; Ayabe, Hiroaki; Ejiri, Yoko; Amimoto, Naoki; Yamazaki, Yosuke; Ogawa, Shimpei; Ishikawa, Momotaro; Kiyota, Yasujiro; Sato, Yasuhiko; Nozawa, Kohei; Okamoto, Satoshi; Ueno, Yasuharu; Taniguchi, Hideki

2017-12-05

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>10 8 ). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

PubMed

Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

2017-10-02

The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing

PubMed Central

Shashi, Vandana; Petrovski, Slavé; Schoch, Kelly; Crimian, Rebecca; Case, Laura E.; Khalid, Roha; El-Dairi, Maysantoine A.; Jiang, Yong-Hui; Mikati, Mohamad A.; Goldstein, David B.

2015-01-01

One of the most promising outcomes of whole-exome sequencing (WES) is the alteration of medical management following an accurate diagnosis in patients with previously unresolved disorders. Although case reports of targeted therapies resulting from WES have been published, there are few reports with long-term follow-up that confirm a sustained therapeutic response. Following a diagnosis by WES of Brown–Vialetto–Van Laere Syndrome 2 (BVVLS2), high-dose riboflavin therapy was instituted in a 20-mo-old child. An immediate clinical response with stabilization of signs and symptoms was noted over the first 2–4 wk. Subsequent clinical follow-up over the following 8 mo demonstrates not just stabilization, but continuing and sustained improvements in all manifestations of this usually fatal condition, which generally includes worsening motor weakness, sensory ataxia, hearing, and vision impairments. This case emphasizes that early application of WES can transform patient care, enabling therapy that in addition to being lifesaving can sometimes reverse the disabling disease processes in a progressive condition. PMID:27148562

Hereditary pancreatic cancer: molecular bases and their application in diagnosis and clinical management: a guideline of the TTD group.

PubMed

Segura, P Pérez; Ponce, C Guillén; Ramón Y Cajal, T; Blanch, R Serrano; Aranda, E

2012-08-01

Pancreatic carcinoma (PC) represents the fourth leading cause of cancer death in Spain with a death rate of 2,400 males and 2,000 females per year. Poor outcome related to its silent nature and the lack of reliable secondary prevention measures translate into advanced-stage diagnosis, 75 % of deaths within the first year of diagnosis and 5-year survival rate of <5 %. Family history was first recognized as a risk factor for PC. Further population-based and case-control studies subsequently found that 7.8 % of patients with PC have a family history of the same tumor and individuals with a first-degree relative with PC have a 3.2-fold increased risk of developing PC. Overall, it is estimated that up to 10 % of PC have a familial component. However, known genetic syndromes account for <20 % of the observed familial aggregation of PC. We review the most important aspects in epidemiology, molecular biology and clinical management of familial PC.

Review of key concepts in magnetic resonance physics.

PubMed

Moore, Michael M; Chung, Taylor

2017-05-01

MR physics can be a challenging subject for practicing pediatric radiologists. Although many excellent texts provide very comprehensive reviews of the field of MR physics at various levels of understanding, the authors of this paper explain several key concepts in MR physics that are germane to clinical practice in a non-rigorous but practical fashion. With the basic understanding of these key concepts, practicing pediatric radiologists can build on their knowledge of current clinical MR techniques and future advances in MR applications. Given the challenges of both the increased need for rapid imaging in non-sedated children and the rapid physiological cardiovascular and respiratory motion in pediatric patients, many advances in complex MR techniques are being applied to imaging these children. The key concepts are as follows: (1) structure of a pulse sequence, (2) k-space, (3) "trade-off triangle" and (4) fat suppression. This review is the first of five manuscripts in a minisymposium on pediatric MR. The authors' goal for this review is to aid in understanding the MR techniques described in the subsequent manuscripts on brain imaging and body imaging in this minisymposium.

Determination of the LD50 of acridine orange via intravenous administration in mice in preparation for clinical application to cancer therapy.

PubMed

Nakamura, Tomoki; Kusuzaki, Katsuyuki; Matsubara, Takao; Matsumine, Akihiko; Asanuma, Kunihiro; Satonaka, Haruhiko; Uchida, Atsumasa; Sudo, Akihiro

2014-01-01

We undertook studies to determine the lethal dose 50 (LD50) of acridine orange (AO) using mice in order to confirm the safety of intravenous administration of AO. We used 40 mice and AO was administered once intravenously. General behavior and mortality were continuously observed for 14 days. At the end of the experiment, all animals were sacrificed for subsequent studies. The LD50 for AO in male and female mice was determined to be 32 mg/kg and 36 mg/kg, respectively. Histopathological abnormalities were observed in only one mouse which died three days after the administration of AO. The other nine mice which died immediately after the administration of AO had no pathological findings in major organs. The clinical use of AO can be kept at 1.0 mg/kg or below and, therefore, intravenous administration of AO might be safe for use as cancer therapy. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

History of biochemical pregnancy was associated with the subsequent reproductive failure among women with recurrent spontaneous abortion.

PubMed

Maesawa, Yoko; Yamada, Hideto; Deguchi, Masashi; Ebina, Yasuhiko

2015-04-01

The aim of this study was to evaluate whether the presence of history of biochemical pregnancy (BP) was associated with clinical characteristics and the subsequent pregnancy outcome among women with recurrent spontaneous abortion (RSA). One-hundred and seventy-five RSA women with two or more clinical pregnancy losses were enrolled. The clinical characteristics were compared between 164 women with history of 0-1 BP (Group A) and 11 women with two or more BP (Group B). The frequency of previous pregnancy loss and history of in vitro fertilization and embryo transfer in Group B was higher than that in Group A; while frequency of secondary RSA in Group B was lower than Group A. The subsequent pregnancy outcome was assessed prospectively; and live-birth rate in Group A (72.9%) was higher (p < 0.05) than that in Group B (41.7%). The incidence of reproductive failure (58.3%, p < 0.05) and spontaneous abortion with normal chromosome (25.0%, p = 0.050) in Group B was higher than those (27.1 and 5.9%, respectively) in Group A. RSA women with two or more BP had higher risk of reproductive failure and spontaneous abortion with normal chromosome together with lower chance of live-birth. The results of the present study involve important information and are helpful for clinical practitioners.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications

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

Acharya, Sahaja; Fischer-Valuck, Benjamin W.; Kashani, Rojano

Purpose: To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. Methods and Materials: The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped {sup 60}Co heads. The unit is supported by a Monte Carlo–based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient atmore » the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. Results: The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. Conclusion: Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.« less

25 CFR 23.34 - Review and decision on off-reservation applications by Area Director.

Code of Federal Regulations, 2011 CFR

2011-04-01

... competitive review and subsequent approval or disapproval of the applications. (b) Area office competitive... required in paragraph (a) of this section. (3) Review the application in accordance with the competitive... area competitive review and scoring process unless a review of the application determines that it: (i...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

Application of image-derived and venous input functions in major depression using [carbonyl-(11)C]WAY-100635.

PubMed

Hahn, Andreas; Nics, Lukas; Baldinger, Pia; Wadsak, Wolfgang; Savli, Markus; Kraus, Christoph; Birkfellner, Wolfgang; Ungersboeck, Johanna; Haeusler, Daniela; Mitterhauser, Markus; Karanikas, Georgios; Kasper, Siegfried; Frey, Richard; Lanzenberger, Rupert

2013-04-01

Image-derived input functions (IDIFs) represent a promising non-invasive alternative to arterial blood sampling for quantification in positron emission tomography (PET) studies. However, routine applications in patients and longitudinal designs are largely missing despite widespread attempts in healthy subjects. The aim of this study was to apply a previously validated approach to a clinical sample of patients with major depressive disorder (MDD) before and after electroconvulsive therapy (ECT). Eleven scans from 5 patients with venous blood sampling were obtained with the radioligand [carbonyl-(11)C]WAY-100635 at baseline, before and after 11.0±1.2 ECT sessions. IDIFs were defined by two different image reconstruction algorithms 1) OSEM with subsequent partial volume correction (OSEM+PVC) and 2) reconstruction based modelling of the point spread function (TrueX). Serotonin-1A receptor (5-HT1A) binding potentials (BPP, BPND) were quantified with a two-tissue compartment (2TCM) and reference region model (MRTM2). Compared to MRTM2, good agreement in 5-HT1A BPND was found when using input functions from OSEM+PVC (R(2)=0.82) but not TrueX (R(2)=0.57, p<0.001), which is further reflected by lower IDIF peaks for TrueX (p<0.001). Following ECT, decreased 5-HT1A BPND and BPP were found with the 2TCM using OSEM+PVC (23%-35%), except for one patient showing only subtle changes. In contrast, MRTM2 and IDIFs from TrueX gave unstable results for this patient, most probably due to a 2.4-fold underestimation of non-specific binding. Using image-derived and venous input functions defined by OSEM with subsequent PVC we confirm previously reported decreases in 5-HT1A binding in MDD patients after ECT. In contrast to reference region modeling, quantification with image-derived input functions showed consistent results in a clinical setting due to accurate modeling of non-specific binding with OSEM+PVC. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of surgical hand scrub time on subsequent bacterial growth.

PubMed

Wheelock, S M; Lookinland, S

1997-06-01

In this experimental study, the researchers evaluated the effect of surgical hand scrub time on subsequent bacterial growth and assessed the effectiveness of the glove juice technique in a clinical setting. In a randomized crossover design, 25 perioperative staff members scrubbed for two or three minutes in the first trial and vice versa in the second trial, after which the wore sterile surgical gloves for one hour under clinical conditions. The researchers then sampled the subjects' nondominant hands for bacterial growth, cultured aliquots from the sampling solution, and counted microorganisms. Scrubbing for three minutes produced lower mean log bacterial counts than scrubbing for two minutes. Although the mean bacterial count differed significantly (P = .02) between the two-minute and three-minute surgical hand scrub times, it fell below 0.5 log, which is the threshold for practical and clinical significance. This finding suggests that a two-minute surgical hand scrub is clinically as effective as a three-minute surgical had scrub. The glove juice technique demonstrated sensitivity and reliability in enumerating bacteria on the hands of perioperative staff members in a clinical setting.

40 CFR 1068.31 - What provisions apply to nonroad or stationary engines that change their status?

Code of Federal Regulations, 2010 CFR

2010-07-01

... nonroad application is subsequently used in an application other than a nonroad application, or when an engine previously used in a stationary application (i.e., an engine that was not used as a nonroad engine... stationary engine becomes a new nonroad engine if— (1) It is used in an application that meets the criteria...

Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane.

PubMed

Yang, Li; Palliyaguru, Dushani L; Kensler, Thomas W

2016-02-01

With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, preclinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular cytogenetics: an indispensable tool for cancer diagnosis.

PubMed

Wan, Thomas Sk; Ma, Edmond Sk

2012-01-01

Cytogenetic aberrations may escape detection or recognition in traditional karyotyping. The past decade has seen an explosion of methodological advances in molecular cytogenetics technology. These cytogenetics techniques add color to the black and white world of conventional banding. Fluorescence in-situ hybridization (FISH) study has emerged as an indispensable tool for both basic and clinical research, as well as diagnostics, in leukemia and cancers. FISH can be used to identify chromosomal abnormalities through fluorescent labeled DNA probes that target specific DNA sequences. Subsequently, FISH-based tests such as multicolor karyotyping, comparative genomic hybridization (CGH) and array CGH have been used in emerging clinical applications as they enable resolution of complex karyotypic aberrations and whole global scanning of genomic imbalances. More recently, crossspecies array CGH analysis has also been employed in cancer gene identification. The clinical impact of FISH is pivotal, especially in the diagnosis, prognosis and treatment decisions for hematological diseases, all of which facilitate the practice of personalized medicine. This review summarizes the methodology and current utilization of these FISH techniques in unraveling chromosomal changes and highlights how the field is moving away from conventional methods towards molecular cytogenetics approaches. In addition, the potential of the more recently developed FISH tests in contributing information to genetic abnormalities is illustrated.

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.

PubMed

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2017-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo . However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa , which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo .

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma.

PubMed

Tamboli, Vibha K; Bhalla, Nikhil; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Bowen, Jenna L; Allender, Chris J; Estrela, Pedro

2016-12-06

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics

PubMed Central

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2018-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo. However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa, which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo. PMID:29375551

Clinical evaluation of endometriosis and differential response to surgical therapy with and without application of Oxiplex/AP* adhesion barrier gel.

PubMed

diZerega, Gere S; Coad, James; Donnez, Jacques

2007-03-01

To correlate parameters of endometriosis obtained during routine clinical evaluation with the subsequent formation of adhesions following surgical treatment by laparoscopy. Randomized, controlled, double-blind, clinical trial. Tertiary referral centers for the treatment of endometriosis. Thirty-seven patients (65 with adnexa) with stage I-III endometriosis; endometrioma-only patients were excluded. Laparoscopic surgical treatment of endometriosis, followed by randomization to Oxiplex/AP (FzioMed, Inc., San Luis Obispo, California) gel treatment (treated group) of adnexa, or surgery alone (control group); follow-up laparoscopy 6-10 weeks later. Adnexal Americn Fertility Society score, correlated with color and location of endometriosis, as well as stage of disease determined by masked review of videotapes. Control patients with at least 50% red lesions had a greater increase in ipsilateral adnexal adhesion scores than patients with mostly black or white and/or clear lesions. Treated patients with red lesions had a greater decrease in adnexal adhesion scores than control patients. There was a correlation between baseline endometriosis stage and postoperative adhesion formation in control patients, but not treated patients. Patients with red endometriotic lesions had greater increases in their adhesion scores than patients with only black, white, and/or clear lesions. Oxiplex/AP gel was effective in reducing adhesions, compared to surgery alone, in all groups.

The history of barbiturates a century after their clinical introduction

PubMed Central

López-Muñoz, Francisco; Ucha-Udabe, Ronaldo; Alamo, Cecilio

2005-01-01

The present work offers an analysis of the historical development of the discovery and use of barbiturates in the field of psychiatry and neurology, a century after their clinical introduction. Beginning with the synthesis of malonylurea by von Baeyer in 1864, and up to the decline of barbiturate therapy in the 1960s, it describes the discovery of the sedative properties of barbital, by von Mering and Fischer (1903), the subsequent synthesis of phenobarbital by this same group (1911), and the gradual clinical incorporation of different barbiturates (butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, etc). We describe the role played in therapy by barbiturates throughout their history: their traditional use as sedative and hypnotic agents, their use with schizophrenic patients in so-called “sleep cures” (Klaesi, Cloetta), the discovery of the antiepileptic properties of phenobarbital (Hauptmann) and their use in the treatment of epilepsy, and the introduction of thiobarbiturates in intravenous anesthesia (Lundy, Waters). We also analyze, from the historical perspective, the problems of safety (phenomena of dependence and death by overdose) which, accompanied by the introduction of a range of psychoactive drugs in the 1950s, brought an end to barbiturate use, except in specific applications, such as the induction of anesthesia and the treatment of certain types of epileptic crisis. PMID:18568113

Insufficient sleep predicts clinical burnout.

PubMed

Söderström, Marie; Jeding, Kerstin; Ekstedt, Mirjam; Perski, Aleksander; Akerstedt, Torbjörn

2012-04-01

The present prospective study aimed to identify risk factors for subsequent clinical burnout. Three hundred eighty-eight working individuals completed a baseline questionnaire regarding work stress, sleep, mood, health, and so forth. During a 2-year period, 15 subjects (7 women and 8 men) of the total sample were identified as "burnout cases," as they were assessed and referred to treatment for clinical burnout. Questionnaire data from the baseline measurement were used as independent variables in a series of logistic regression analyses to predict clinical burnout. The results identified "too little sleep (< 6 h)" as the main risk factor for burnout development, with adjustment for "work demands," "thoughts of work during leisure time," and "sleep quality." The first two factors were significant predictors in earlier steps of the multivariate regression. The results indicate that insufficient sleep, preoccupation with thoughts of work during leisure time, and high work demands are risk factors for subsequent burnout. The results suggest a chain of causation. PsycINFO Database Record (c) 2012 APA, all rights reserved.

A Retrospective Study of Paresthesia of the Dental Alveolar Nerves

PubMed Central

Nickel, Alfred A.

1990-01-01

Paresthesia is a rare clinical finding subsequent to surgery accompanied by the administration of local anesthetics. A small patient population was identified whose clinical problem may be explained by neurotoxicity due to a local anesthetic metabolite. Reasonable questions arise from these clinical observations that would benefit from prospective studies to explain sensory loss on a biochemical basis. PMID:2077986

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

PubMed

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice.

PubMed

Souberbielle, Jean-Claude; Body, Jean-Jacques; Lappe, Joan M; Plebani, Mario; Shoenfeld, Yehuda; Wang, Thomas J; Bischoff-Ferrari, Heike A; Cavalier, Etienne; Ebeling, Peter R; Fardellone, Patrice; Gandini, Sara; Gruson, Damien; Guérin, Alain P; Heickendorff, Lene; Hollis, Bruce W; Ish-Shalom, Sofia; Jean, Guillaume; von Landenberg, Philipp; Largura, Alvaro; Olsson, Tomas; Pierrot-Deseilligny, Charles; Pilz, Stefan; Tincani, Angela; Valcour, Andre; Zittermann, Armin

2010-09-01

There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D(2) and 25(OH)D(3) is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing. Copyright 2010 Elsevier B.V. All rights reserved.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

Laser ablation of hard tissue: correlation between the laser beam parameters and the post-ablative tissue characteristics

NASA Astrophysics Data System (ADS)

Serafetinides, Alexandros A.; Makropoulou, Mersini I.; Khabbaz, Maruan

2003-11-01

Hard dental tissue laser applications, such as preventive treatment, laser diagnosis of caries, laser etching of enamel, laser decay removal and cavity preparation, and more recently use of the laser light to enlarge the root canal during the endodontic therapy, have been investigated for in vitro and in vivo applications. Post-ablative surface characteristics, e.g. degree of charring, cracks and other surface deformation, can be evaluated using scanning electron microscopy. The experimental data are discussed in relevance with the laser beam characteristics, e.g. pulse duration, beam profile, and the beam delivery systems employed. Techniques based on the laser illumination of the dental tissues and the subsequent evaluation of the scattered fluorescent light will be a valuable tool in early diagnosis of tooth diseases, as carious dentin or enamel. The laser induced autofluorescence signal of healthy dentin is much stronger than that of the carious dentin. However, a better understanding of the transmission patterns of laser light in teeth, for both diagnosis and therapy is needed, before the laser procedures can be used in a clinical environment.

In vitro cell system for studying molecular mechanisms of action associated with low intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Babakhanian, Meghedi; Fan, Richard E.; Mulgaonkar, Amit P.; Singh, Rahul; Culjat, Martin O.; Danesh, Shahab M.; Toro, Ligia; Grundfest, Warren; Melega, William P.

2012-03-01

Low intensity focused ultrasound (LIFU) is now being considered as a noninvasive brain therapy for clinical applications. We maintain that LIFU can efficiently deliver energy from outside the skull to target specific brain regions, effecting localized neuromodulation. However, the underlying molecular mechanisms that drive this LIFU-induced neuromodulation are not well-defined due, in part, to our lack of understanding of how particular sets of LIFU delivery parameters affect the outcome. To efficiently conduct multiple sweeps of different parameters and determine their effects, we have developed an in-vitro system to study the effects of LIFU on different types of cells grown in culture. Presently, we are evaluating how LIFU affects the ionic flux that may underlie neuronal excitation and inhibition observed in-vivo. The results of our in-vitro studies will provide a rationale for selection of optimal LIFU parameter to be used in subsequent in-vivo applications. Thus, a prototype ultrasound cell assay system has been developed to conduct these studies, and is described in this work.

In-depth Characterization of a TCR-specific Tracer for Sensitive Detection of Tumor-directed Transgenic T Cells by Immuno-PET.

PubMed

Yusufi, Nahid; Mall, Sabine; Bianchi, Henrique de Oliveira; Steiger, Katja; Reder, Sybille; Klar, Richard; Audehm, Stefan; Mustafa, Mona; Nekolla, Stephan; Peschel, Christian; Schwaiger, Markus; Krackhardt, Angela M; D'Alessandria, Calogero

2017-01-01

A number of different technologies have been developed to monitor in vivo the distribution of gene-modified T cells used in immunotherapy. Nevertheless, in-depth characterization of novel approaches with respect to sensitivity and clinical applicability are so far missing. We have previously described a novel method to track engineered human T cells in tumors using 89 Zr-Df-aTCRmu-F(ab') 2 targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR. Here, we performed an in-depth in vitro characterization of the tracer in terms of antigen affinity, immunoreactivity, influence on T-cell functionality and stability in vitro and in vivo . Of particular interest, we have developed diverse experimental settings to quantify TCR-transgenic T cells in vivo . Local application of 89 Zr-Df-aTCRmu-F(ab') 2 -labeled T cells in a spot-assay revealed signal detection down to approximately 1.8x10 4 cells. In a more clinically relevant model, NSG mice were intravenously injected with different numbers of transgenic T cells, followed by injection of the 89 Zr-Df-aTCRmu-F(ab') 2 tracer, PET/CT imaging and subsequent ex vivo T-cell quantification in the tumor. Using this setting, we defined a comparable detection limit of 1.0x10 4 T cells. PET signals correlated well to total numbers of transgenic T cells detected ex vivo independently of the engraftment rates observed in different individual experiments. Thus, these findings confirm the high sensitivity of our novel PET/CT T-cell tracking method and provide critical information about the quantity of transgenic T cells in the tumor environment suggesting our technology being highly suitable for further clinical translation.

Ultrasound-guided microwave ablation in the treatment of benign thyroid nodules in 435 patients

PubMed Central

Qian, Lin-Xue; Liu, Dong; Zhao, Jun-Feng

2017-01-01

The objective of the present study was to investigate the effectiveness and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules. A total of 474 benign thyroid nodules in 435 patients who underwent ultrasound-guided microwave ablation from September 2012 to August 2015 were included. Nodule volume and thyroid function were measured before treatment and at 1, 3, 6, and 12 months and subsequently after every 6 months. The nodule volume reduction rate and changes of thyroid function were evaluated. The volume of all thyroid nodules significantly decreased after ultrasound-guided microwave ablation. The average volume was 13.07 ± 0.95 ml before treatment, and 1.14 ± 0.26 ml at 12-months follow-up. The mean volume reduction rate was 90% and the final volume reduction rate was 94%. The volume reduction rate of mainly cystic nodules was significantly higher than that of simple solid and mainly solid nodules (all P < 0.05). The pretreatment volume of nodules was positively correlated with the final volume reduction rate at final follow-up (P = 0.004). No serious complications were observed after treatment. In conclusion, ultrasound-guided microwave ablation is an effective and safe technique for treatment of benign thyroid nodules, and has the potential for clinical applications. Impact statement Ultrasound-guided MWA is an effective and safe technique for the treatment of benign thyroid nodules. It can significantly reduce the nodule volume, improve the patients’ clinical symptoms, has less complication, guarantees quick recovery, meets patients' aesthetic needs, and shows less interference on the physiological and psychological aspects of the body. MWA should be a good complement to traditional open surgery and has potentials in clinical applications. PMID:28847173

Ultrasound-guided microwave ablation in the treatment of benign thyroid nodules in 435 patients.

PubMed

Liu, Yu-Jiang; Qian, Lin-Xue; Liu, Dong; Zhao, Jun-Feng

2017-09-01

The objective of the present study was to investigate the effectiveness and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules. A total of 474 benign thyroid nodules in 435 patients who underwent ultrasound-guided microwave ablation from September 2012 to August 2015 were included. Nodule volume and thyroid function were measured before treatment and at 1, 3, 6, and 12 months and subsequently after every 6 months. The nodule volume reduction rate and changes of thyroid function were evaluated. The volume of all thyroid nodules significantly decreased after ultrasound-guided microwave ablation. The average volume was 13.07 ± 0.95 ml before treatment, and 1.14 ± 0.26 ml at 12-months follow-up. The mean volume reduction rate was 90% and the final volume reduction rate was 94%. The volume reduction rate of mainly cystic nodules was significantly higher than that of simple solid and mainly solid nodules (all P < 0.05). The pretreatment volume of nodules was positively correlated with the final volume reduction rate at final follow-up ( P = 0.004). No serious complications were observed after treatment. In conclusion, ultrasound-guided microwave ablation is an effective and safe technique for treatment of benign thyroid nodules, and has the potential for clinical applications. Impact statement Ultrasound-guided MWA is an effective and safe technique for the treatment of benign thyroid nodules. It can significantly reduce the nodule volume, improve the patients' clinical symptoms, has less complication, guarantees quick recovery, meets patients' aesthetic needs, and shows less interference on the physiological and psychological aspects of the body. MWA should be a good complement to traditional open surgery and has potentials in clinical applications.

Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors

PubMed Central

Ravikumar, Balaguru; Parri, Elina; Timonen, Sanna; Airola, Antti; Wennerberg, Krister

2017-01-01

Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds, various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification. However, most of the model predictions lack direct experimental validation in the laboratory, making their practical benefits for drug discovery or repurposing applications largely unknown. Here, we therefore introduce and carefully test a systematic computational-experimental framework for the prediction and pre-clinical verification of drug-target interactions using a well-established kernel-based regression algorithm as the prediction model. To evaluate its performance, we first predicted unmeasured binding affinities in a large-scale kinase inhibitor profiling study, and then experimentally tested 100 compound-kinase pairs. The relatively high correlation of 0.77 (p < 0.0001) between the predicted and measured bioactivities supports the potential of the model for filling the experimental gaps in existing compound-target interaction maps. Further, we subjected the model to a more challenging task of predicting target interactions for such a new candidate drug compound that lacks prior binding profile information. As a specific case study, we used tivozanib, an investigational VEGF receptor inhibitor with currently unknown off-target profile. Among 7 kinases with high predicted affinity, we experimentally validated 4 new off-targets of tivozanib, namely the Src-family kinases FRK and FYN A, the non-receptor tyrosine kinase ABL1, and the serine/threonine kinase SLK. Our sub-sequent experimental validation protocol effectively avoids any possible information leakage between the training and validation data, and therefore enables rigorous model validation for practical applications. These results demonstrate that the kernel-based modeling approach offers practical benefits for probing novel insights into the mode of action of investigational compounds, and for the identification of new target selectivities for drug repurposing applications. PMID:28787438

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study.

PubMed

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-06-24

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera -based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson's Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence ( p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant ( p < 0.02). Conclusions : Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer.

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study

PubMed Central

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-01-01

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera-based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson’s Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence (p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant (p < 0.02). Conclusions: Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer. PMID:28930258

Fabrication of Calcium Phosphate-Based Nanocomposites Incorporating DNA Origami, Gold Nanorods, and Anticancer Drugs for Biomedical Applications.

PubMed

Zhang, Hongbo; Qu, Xiangmeng; Chen, Hong; Kong, Haixin; Ding, Ruihua; Chen, Dong; Zhang, Xu; Pei, Hao; Santos, Hélder A; Hai, Mingtan; Weitz, David A

2017-10-01

DNA origami is designed by folding DNA strands at the nanoscale with arbitrary control. Due to its inherent biological nature, DNA origami is used in drug delivery for enhancement of synergism and multidrug resistance inhibition, cancer diagnosis, and many other biomedical applications, where it shows great potential. However, the inherent instability and low payload capacity of DNA origami restrict its biomedical applications. Here, this paper reports the fabrication of an advanced biocompatible nano-in-nanocomposite, which protects DNA origami from degradation and facilities drug loading. The DNA origami, gold nanorods, and molecular targeted drugs are co-incorporated into pH responsive calcium phosphate [Ca 3 (PO 4 ) 2 ] nanoparticles. Subsequently, a thin layer of phospholipid is coated onto the Ca 3 (PO 4 ) 2 nanoparticle to offer better biocompatibility. The fabricated nanocomposite shows high drug loading capacity, good biocompatibility, and a photothermal and pH-responsive payload release profile and it fully protects DNA origami from degradation. The codelivery of DNA origami with cancer drugs synergistically induces cancer cell apoptosis, reduces the multidrug resistance, and enhances the targeted killing efficiency toward human epidermal growth factor receptor 2 positive cells. This nanocomposite is foreseen to open new horizons for a variety of clinical and biomedical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

78 FR 77118 - KC Small Hydro, LLC; Notice of Amended Preliminary Permit Application Accepted for Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

..., Motions To Intervene, and Competing Applications On May 28, 2013, KC Scoby Hydro, LLC, filed an... 28, 2013, application and sent an acceptance letter to KC Scoby Hydro, LLC. Subsequently, On October 28, 2013, KC Scoby Hydro, LLC, amended its preliminary permit application to change its name to KC...

Applicability of initial optimal maternal and fetal electrocardiogram combination vectors to subsequent recordings

NASA Astrophysics Data System (ADS)

Yan, Hua-Wen; Huang, Xiao-Lin; Zhao, Ying; Si, Jun-Feng; Liu, Tie-Bing; Liu, Hong-Xing

2014-11-01

A series of experiments are conducted to confirm whether the vectors calculated for an early section of a continuous non-invasive fetal electrocardiogram (fECG) recording can be directly applied to subsequent sections in order to reduce the computation required for real-time monitoring. Our results suggest that it is generally feasible to apply the initial optimal maternal and fetal ECG combination vectors to extract the fECG and maternal ECG in subsequent recorded sections.

A Case of Depression Screening in Schools

ERIC Educational Resources Information Center

Miloseva, Lence

2016-01-01

Adolescent clinical and subclinical depression has a significant negative impact on adolescents well being, school performance and consequently produces maladaptive outcomes in terms of subsequent education and occupational functioning. This research is a part of a larger research project with a focus on clinical and subclinical depression during…

Behavioral responses to two intranasal vaccine applicators in horses and ponies.

PubMed

Grogan, Elkanah H; McDonnell, Sue M

2005-05-15

To evaluate behavioral compliance of horses and ponies with simulated intranasal vaccination and assess development of generalized aversion to veterinary manipulations. Clinical trial. 28 light horse mares, 3 pony geldings, 2 light horse stallions, and 3 pony stallions that had a history of compliance with veterinary procedures. Behavioral compliance with 2 intranasal vaccine applicators was assessed. Compliance with standard physical examination procedures was assessed before and after a single experience with either of the applicators or a control manipulation to evaluate development of generalized aversion to veterinary manipulation. In all 30 horses, simulated intranasal vaccination or the control manipulation could be performed without problematic avoidance behavior, and simulated intranasal vaccination did not have any significant effect on duration of or compliance with a standardized physical examination that included manipulation of the ears, nose, and mouth. Results were similar for the 2 intranasal vaccine applicators, and no difference in compliance was seen between horses in which warm versus cold applicators were used. For 3 of the 6 ponies, substantial avoidance behavior was observed in association with simulated intranasal vaccination, and compliance with physical examination procedures decreased after simulated intranasal vaccination. Although some compliance problems were seen with ponies, neither problems with compliance with simulated intranasal vaccination nor adverse effects on subsequent physical examination were identified in any of the horses. Further study is needed to understand factors involved in practitioner reports of aversion developing in association with intranasal vaccination.

Cost-effective system for facial imaging and three-dimensional reconstruction

NASA Astrophysics Data System (ADS)

Shokouhi, S. B.; Monro, D. M.; Sherlock, Barry G.

1998-06-01

Three dimensional (3-D) images have recently received wide attention in applications involving medical treatment. Most current 3-D imaging methods focus on the internal organs of the body. However, several medical image applications such as plastic surgery, body deformities, rehabilitation, dental surgery and orthodontics, make use of the surface contours of the body. Several techniques are currently available for producing 3-D images of the body surface and most of the systems which implement these techniques are expensive, requiring complex equipment with highly trained operators. The research involves the development of a simple, low cost and non-invasive contour capturing method for facial surfaces. This is achieved using the structured light technique, employing a standard commercial slide projector, CCD camera and a frame-grabber card linked to a PC. Structured light has already been used for many applications, but only to a limited extent in the clinical environment. All current implementations involve extensive manual intervention by highly skilled operators and this has proven to be a serious hindrance to clinical acceptance of 3-D imaging. A primary objective of this work is to minimize the amount of manual intervention required, so that the system can be used by clinicians who do not have specialist training in the use of this equipment. The eventual aim is to provide a software assisted surgical procedure, which by merging the facial data, allows the manipulation of soft tissue and gives the facility to predict and monitor post-surgical appearance. The research focuses on how the images are obtained using the structured light optic system and the subsequent image processing of data to give a realistic 3-D image.

Novel Antibiofilm Chemotherapy Targets Exopolysaccharide Synthesis and Stress Tolerance in Streptococcus mutans To Modulate Virulence Expression In Vivo

PubMed Central

Falsetta, Megan L.; Klein, Marlise I.; Lemos, José A.; Silva, Bruno B.; Agidi, Senyo; Scott-Anne, Kathy K.

2012-01-01

Fluoride is the mainstay of dental caries prevention, and yet current applications offer incomplete protection and may not effectively address the infectious character of the disease. Therefore, we evaluated the effectiveness of a novel combination therapy (CT; 2 mM myricetin, 4 mM tt-farnesol, 250 ppm of fluoride) that supplements fluoride with naturally occurring, food-derived, antibiofilm compounds. Treatment regimens simulating those experienced clinically (twice daily for ≤60 s) were used both in vitro over a saliva-coated hydroxyapatite biofilm model and in vivo with a rodent model of dental caries. The effectiveness of CT was evaluated based on the incidence and severity of carious lesions (compared to fluoride or vehicle control). We found that CT was superior to fluoride (positive control, P < 0.05); topical applications dramatically reduced caries development in Sprague-Dawley rats, all without altering the Streptococcus mutans or total populations within the plaque. We subsequently identified the underlying mechanisms through which applications of CT modulate biofilm virulence. CT targets expression of key Streptococcus mutans genes during biofilm formation in vitro and in vivo. These are associated with exopolysaccharide matrix synthesis (gtfB) and the ability to tolerate exogenous stress (e.g., sloA), which are essential for cariogenic biofilm assembly. We also identified a unique gene (SMU.940) that was severely repressed and may represent a potentially novel target; its inactivation disrupted exopolysaccharide accumulation and matrix development. Altogether, CT may be clinically more effective than current anticaries modalities, targeting expression of bacterial virulence associated with pathogenesis of the disease. These observations may have relevance for development of enhanced therapies against other biofilm-dependent infections. PMID:22985885

'Care for Stroke', a web-based, smartphone-enabled educational intervention for management of physical disabilities following stroke: feasibility in the Indian context.

PubMed

Sureshkumar, K; Murthy, G V S; Munuswamy, Suresh; Goenka, Shifalika; Kuper, Hannah

2015-07-01

Stroke rehabilitation is a process targeted towards restoration or maintenance of the physical, mental, intellectual and social abilities of an individual affected by stroke. Unlike high-income countries, the resources for stroke rehabilitation are very limited in many low-income and middle-income countries (LMICs). Provision of cost-effective, post-stroke multidisciplinary rehabilitation services for the stroke survivors therefore becomes crucial to address the unmet needs and growing magnitude of disability experienced by the stroke survivors in LMICs. In order to meet the growing need for post-stroke rehabilitation services in India, we developed a web-based Smartphone-enabled educational intervention for management of physical disabilities following a stroke. On the basis of the findings from the rehabilitation needs assessment study, guidance from the expert group and available evidence from systematic reviews, the framework of the intervention content was designed. Web-based application designing and development by Professional application developers were subsequently undertaken. The application is called 'Care for Stroke'. It is a web-based educational intervention for management of physical disabilities following a stroke. This intervention is developed for use by the Stroke survivors who have any kind of rehabilitation needs to independently participate in his/her family and social roles. 'Care for stroke' is an innovative intervention which could be tested not just for its feasibility and acceptability but also for its clinical and cost-effectiveness through rigorously designed, randomised clinical trials. It is very important to test this intervention in LMICs where the rehabilitation and information needs of the stroke survivors seem to be substantial and largely unmet.

37 CFR 1.121 - Manner of making amendments in applications.

Code of Federal Regulations, 2012 CFR

2012-07-01

... subsequent amendment document. Once a paragraph or section is amended in a first amendment document, the... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Manner of making amendments... Provisions Amendments § 1.121 Manner of making amendments in applications. (a) Amendments in applications...

37 CFR 1.121 - Manner of making amendments in applications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... subsequent amendment document. Once a paragraph or section is amended in a first amendment document, the... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Manner of making amendments... Provisions Amendments § 1.121 Manner of making amendments in applications. (a) Amendments in applications...

18 CFR 5.5 - Notification of intent.

Code of Federal Regulations, 2010 CFR

2010-04-01

...'s intention to file an application for an original license, or, in the case of an existing licensee..., DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT INTEGRATED LICENSE APPLICATION PROCESS § 5.5... that it intends to file an application for an original, new, or subsequent license, or for an existing...

Residual effect of poultry litter applications on no-till cotton lint yield

USDA-ARS?s Scientific Manuscript database

In no-till cotton production systems, the potential residual benefits from prior years of poultry litter application are not well known. This study investigated the productivity of no-till cotton fertilized or unfertilized with synthetic N in years subsequent to the last application of suboptimal po...

Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

NASA Astrophysics Data System (ADS)

Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

2008-02-01

Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

Biofuel cell based self-powered sensing platform for L-cysteine detection.

PubMed

Hou, Chuantao; Fan, Shuqin; Lang, Qiaolin; Liu, Aihua

2015-03-17

L-cysteine (L-Cys) detection is of great importance because of its crucial roles in physiological and clinical diagnoses. In this study, a glucose/O2 biofuel cell (BFC) was assembled by using flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH)-based bioanode and laccase-based biocathode. Interestingly, the open circuit potential (OCP) of the BFC could be inhibited by Cu(2+) and subsequently activated by L-Cys, by which a BFC-based self-powered sensing platform for the detection of L-Cys was proposed. The FAD-GDH activity can be inhibited by Cu(2+) and, in turn, subsequent reversible activation by L-Cys because of the binding preference of L-Cys toward Cu(2+) by forming the Cu-S bond. The preferential interaction between L-Cys and Cu(2+) facilitated Cu(2+) to remove from the surface of the bioanode, and thus, the OCP of the system could be turned on. Under optimized conditions, the OCP of the BFC was systematically increased upon the addition of the L-Cys. The OCP increment (ΔOCP) was linear with the concentration of L-Cys within 20 nM to 3 μM. The proposed sensor exhibited lower detection limit of 10 nM L-Cys (S/N = 3), which is significantly lower than those values for other methods reported so far. Other amino acids and glutathione did not affect L-Cys detection. Therefore, this developed approach is sensitive, facile, cost-effective, and environmental-friendly, and could be very promising for the reliable clinically detecting of L-Cys. This work would trigger the interest of developing BFCs based self-powered sensors for practical applications.

Common data manipulations with R in biological researches

PubMed Central

Liu, Qin

2017-01-01

R is a computer language and has been widely used in science community due to the powerful capability in data analysis and visualization; and these functions are mainly provided by the developed packages. Because every package has strict format definitions on the inputted data, it is always required to appropriately manipulate the original data in advance. Unfortunately, users, especially for the beginners, are always confused by the extreme flexibility with R in data manipulation. In the present paper, we roughly categorize the common manipulations with R for biological data into four classes, including overview of data, transformation, summarization, and reshaping. Subsequently, these manipulations are exemplified in a sample data of clinical records of diabetic patients. Our main purpose is to provide a better landscape on the data manipulation with R and hence facilitate the practical applications in biological researches. PMID:28840022

Cell-Extracellular Matrix Mechanobiology: Forceful Tools and Emerging Needs for Basic and Translational Research.

PubMed

Holle, Andrew W; Young, Jennifer L; Van Vliet, Krystyn J; Kamm, Roger D; Discher, Dennis; Janmey, Paul; Spatz, Joachim P; Saif, Taher

2018-01-10

Extracellular biophysical cues have a profound influence on a wide range of cell behaviors, including growth, motility, differentiation, apoptosis, gene expression, adhesion, and signal transduction. Cells not only respond to definitively mechanical cues from the extracellular matrix (ECM) but can also sometimes alter the mechanical properties of the matrix and hence influence subsequent matrix-based cues in both physiological and pathological processes. Interactions between cells and materials in vitro can modify cell phenotype and ECM structure, whether intentionally or inadvertently. Interactions between cell and matrix mechanics in vivo are of particular importance in a wide variety of disorders, including cancer, central nervous system injury, fibrotic diseases, and myocardial infarction. Both the in vitro and in vivo effects of this coupling between mechanics and biology hold important implications for clinical applications.

Airborne polycyclic aromatic hydrocarbons trigger human skin cells aging through aryl hydrocarbon receptor.

PubMed

Qiao, Yuan; Li, Qiang; Du, Hong-Yang; Wang, Qiao-Wei; Huang, Ye; Liu, Wei

2017-07-01

Accumulating evidence suggests that polycyclic aromatic hydrocarbons (PAH) which adsorbed on the surface of ambient air particulate matters (PM), are the major toxic compound to cause cardiovascular and respiratory diseases, even cancer. However, its detrimental effects on human skin cell remain unclear. Here, we demonstrated that SRM1649b, a reference urban dust material of PAH, triggers human skin cells aging through cell cycle arrest, cell growth inhibition and apoptosis. Principally, SRM1649b facilitated Aryl hydrocarbon receptor (AhR) translocated into nucleus, subsequently activated ERK/MAPK signaling pathway, and upregulated aging-related genes expression. Most important, we found that AhR antagonist efficiently revert the aging of skin cells. Thus our novel findings firstly revealed the mechanism of skin aging under PAH contamination and provided potential strategy for clinical application. Copyright © 2017. Published by Elsevier Inc.

Boron absorption imaging in rat lung colon adenocarcinoma metastases

NASA Astrophysics Data System (ADS)

Altieri, S.; Bortolussi, S.; Bruschi, P.; Fossati, F.; Vittor, K.; Nano, R.; Facoetti, A.; Chiari, P.; Bakeine, J.; Clerici, A.; Ferrari, C.; Salvucci, O.

2006-05-01

Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher 10B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of 10B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

A machine learning approach to triaging patients with chronic obstructive pulmonary disease

PubMed Central

Qirko, Klajdi; Smith, Ted; Corcoran, Ethan; Wysham, Nicholas G.; Bazaz, Gaurav; Kappel, George; Gerber, Anthony N.

2017-01-01

COPD patients are burdened with a daily risk of acute exacerbation and loss of control, which could be mitigated by effective, on-demand decision support tools. In this study, we present a machine learning-based strategy for early detection of exacerbations and subsequent triage. Our application uses physician opinion in a statistically and clinically comprehensive set of patient cases to train a supervised prediction algorithm. The accuracy of the model is assessed against a panel of physicians each triaging identical cases in a representative patient validation set. Our results show that algorithm accuracy and safety indicators surpass all individual pulmonologists in both identifying exacerbations and predicting the consensus triage in a 101 case validation set. The algorithm is also the top performer in sensitivity, specificity, and ppv when predicting a patient’s need for emergency care. PMID:29166411

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

PubMed

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-02-16

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

Quality assessment of crude and processed Arecae semen based on colorimeter and HPLC combined with chemometrics methods.

PubMed

Sun, Meng; Yan, Donghui; Yang, Xiaolu; Xue, Xingyang; Zhou, Sujuan; Liang, Shengwang; Wang, Shumei; Meng, Jiang

2017-05-01

Raw Arecae Semen, the seed of Areca catechu L., as well as Arecae Semen Tostum and Arecae semen carbonisata are traditionally processed by stir-baking for subsequent use in a variety of clinical applications. These three Arecae semen types, important Chinese herbal drugs, have been used in China and other Asian countries for thousands of years. In this study, the sensory technologies of a colorimeter and sensitive validated high-performance liquid chromatography with diode array detection were employed to discriminate raw Arecae semen and its processed drugs. The color parameters of the samples were determined by a colorimeter instrument CR-410. Moreover, the fingerprints of the four alkaloids of arecaidine, guvacine, arecoline and guvacoline were surveyed by high-performance liquid chromatography. Subsequently, Student's t test, the analysis of variance, fingerprint similarity analysis, hierarchical cluster analysis, principal component analysis, factor analysis and Pearson's correlation test were performed for final data analysis. The results obtained demonstrated a significant color change characteristic for components in raw Arecae semen and its processed drugs. Crude and processed Arecae semen could be determined based on colorimetry and high-performance liquid chromatography with a diode array detector coupled with chemometrics methods for a comprehensive quality evaluation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cardiac registers: the adult cardiac surgery register.

PubMed

Bridgewater, Ben

2010-09-01

AIMS OF THE SCTS ADULT CARDIAC SURGERY DATABASE: To measure the quality of care of adult cardiac surgery in GB and Ireland and provide information for quality improvement and research. Feedback of structured data to hospitals, publication of named hospital and surgeon mortality data, publication of benchmarked activity and risk adjusted clinical outcomes through intermittent comprehensive database reports, annual screening of all hospital and individual surgeon risk adjusted mortality rates by the professional society. All NHS hospitals in England, Scotland and Wales with input from some private providers and hospitals in Ireland. 1994-ongoing. Consecutive patients, unconsented. Current number of records: 400000. Adult cardiac surgery operations excluding cardiac transplantation and ventricular assist devices. 129 fields covering demographic factors, pre-operative risk factors, operative details and post-operative in-hospital outcomes. Entry onto local software systems by direct key board entry or subsequent transcription from paper records, with subsequent electronic upload to the central cardiac audit database. Non-financial incentives at hospital level. Local validation processes exist in the hospitals. There is currently no external data validation process. All cause mortality is obtained through linkage with Office for National Statistics. No other linkages exist at present. Available for research and audit by application to the SCTS database committee at http://www.scts.org.

The pulling power of chocolate: Effects of approach-avoidance training on approach bias and consumption.

PubMed

Dickson, Hugh; Kavanagh, David J; MacLeod, Colin

2016-04-01

Previous research has shown that action tendencies to approach alcohol may be modified using computerized Approach-Avoidance Task (AAT), and that this impacted on subsequent consumption. A recent paper in this journal (Becker, Jostman, Wiers, & Holland, 2015) failed to show significant training effects for food in three studies: Nor did it find effects on subsequent consumption. However, avoidance training to high calorie foods was tested against a control rather than Approach training. The present study used a more comparable paradigm to the alcohol studies. It randomly assigned 90 participants to 'approach' or 'avoid' chocolate images on the AAT, and then asked them to taste and rate chocolates. A significant interaction of condition and time showed that training to avoid chocolate resulted in faster avoidance responses to chocolate images, compared with training to approach it. Consistent with Becker et al.'s Study 3, no effect was found on amounts of chocolate consumed, although a newly published study in this journal (Schumacher, Kemps, & Tiggemann, 2016) did do so. The collective evidence does not as yet provide solid basis for the application of AAT training to reduction of problematic food consumption, although clinical trials have yet to be conducted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical Features of Ocular Toxocariasis in Adult Korean Patients.

PubMed

Jee, Donghyun; Kim, Kyu Seop; Lee, Won Ki; Kim, Wungjae; Jeon, Sohee

2016-01-01

To investigate the clinical characteristics and treatment results of adult patients with ocular toxocariasis. A total of 54 consecutive patients who were clinically and serologically diagnosed with ocular toxocariasis were retrospectively reviewed. Among patients, 66.7 and 77.3% showed increases in eosinophil cationic protein (ECP) and total Ig E in serum, respectively. Four eyes (7.2%) initially presented as neuroretinitis with subsequent motile retinal lesion. The recurrence rates in the combination treatment group with albendazole and corticosteroids were significantly lower than those in the steroid-alone group during the mean follow-up of 27.6 months (p = 0.001). The adjunctive test of serum total IgE level may be helpful for the diagnosis of ocular toxocariasis. Ocular toxocariasis should be considered in the differential diagnosis of unilateral neuroretinitis with subsequent motile retinal lesion. Combined treatment with albendazole and corticosteroids appeared to be effective for reducing the recurrence of intraocular inflammation.

Dental Hygienists' Perceptions of Preparedness for Clinical Practice: A Phenomenological Study

ERIC Educational Resources Information Center

Cantrell, Lezlie M.

2012-01-01

The purpose of this phenomenological study was to identify, compile, and describe how community college graduate dental hygienists perceived their initial dental hygiene curriculum preparation and how they subsequently adapted their curriculum preparation in order to perform their responsibilities in their first clinical dental hygiene job.…

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

ERIC Educational Resources Information Center

Garrido, Melissa Downey

2012-01-01

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

A double-blind, randomized clinical study to determine the efficacy of benzocaine 10% on histamine-induced pruritus and UVB-light induced slight sunburn pain.

PubMed

Bauer, Martin; Schwameis, Richard; Scherzer, Thomas; Lang-Zwosta, Isabelle; Nishino, Kanako; Zeitlinger, Markus

2015-01-01

This study aims to explore the efficacy of the topical application of 10% benzocaine for treating pruritus and pain as compared to vehicle ointment. Twenty male subjects were treated in a randomized double-blind fashion with the investigational medicinal product (IMPD) and vehicle. Immediately after the injection of 100 µg histamine on both arms, subjects received topical treatment and pruritus was subsequently assessed with visual analogue scale (VASpruritus) and Eppendorfer questionnaire. Ultraviolet B radiation (UVB) was administered on the back to induce slight sunburn. Twelve hours after UVB application again the IMPD was applied on the right or left upper back and vehicle on the other side and pain related to sunburn was measured with VASpain and pressure algometry. A trend towards better reduction of pruritus was shown for benzocaine in VASpruritus. For the VASpain significant differences in group comparison (p = 0.02) were observed. Algometer measurements showed onset of pain reduction in the verum group after 20 min whereas in the vehicle-treated area pain relief occurred only after 60 min after application. The topically administered ointment containing 10% benzocaine was found superior over vehicle for treating pain, but not pruritus.

Management factors associated with the incidence of clinical mastitis over the non-lactation period and bulk tank somatic cell count during the subsequent lactation.

PubMed

McDougall, S

2003-04-01

To evaluate associations between management decisions related to the control of mastitis, including the infusion of antibiotics at the end of lactation (dry-cow therapy; DCT), on the incidence of clinical mastitis over the non-lactating period and the bulk tank somatic cell count (BTSCC) in the subsequent lactation. Dairy herd owners (n=158) provided information via a retrospective survey about (a) the proportion of their herds treated with DCT; (b) DCT management, including: number of occasions on which cows were dried off; manipulation of feed and water intake around drying off; infusion technique (partial vs full depth insertion of cannula); and hygiene before and after DCT infusion; (c) occurrence of mastitis and frequency of occurrence following drying off and in the subsequent lactation; (d) number of cows culled for mastitis-related conditions; (e) reasons for culling; (f) incidence of clinical mastitis; and (g) stock purchase policy with regard to mastitis. The BTSCC for each vat of milk supplied for the 1999/2000 and 2000/2001 seasons, and records of antibiotic purchases were collated for each herd. The probability that >2% of cows within a herd were diagnosed with clinical mastitis over the dry period was initially examined using univariate analysis (i.e. chi2 or logistic regression) and associated factors (p<0.2) were offered to a reverse stepwise logistic regression model. Factors hypothesised as being associated with the average lactation log10 BTSCC for the 2000/2001 season were initially examined using univariate analysis (i.e. ANOVA or linear regression analysis) and associated factors (p<0.2) were then tested using a forward manual model-building approach. Increasing the percentage of the herd treated with DCT at the end of lactation was associated with reduced probability that >2% of a herd would be diagnosed with clinical mastitis over the non-lactating period and with a lower BTSCC in the subsequent lactation (p<0.01). A lower BTSCC was associated with small herds (<150 cows; p<0.05), not reducing feed intake around drying off (p<0.05), checking for clinical mastitis over the dry period in the milking parlour rather than at pasture (p<0.05), partial insertion of the DCT cannula (p<0.01), and use of 'change in udder shape' during lactation as a diagnostic criterion for mastitis (p<0.05). The incidence of clinical mastitis over the dry period was positively associated with reduced feeding around drying off (p=0.05) and the estimated volume of milk being produced at the time of drying off (p=0.014). Use of dry cow therapy was associated with fewer cases of clinical mastitis over the non-lactating period and reduced BTSCC over the subsequent lactation. Reduced BTSCC was also associated with smaller herds, use of partial (compared with full depth) insertion of the DCT cannula, not reducing feed intake at the time of drying off, checking for clinical mastitis over the dry (non-lactation) period in the milking parlour, and use of udder shape for diagnosis during lactation. Control of clinical mastitis and BTSCC involves a range of management practices that need to be used in conjunction with DCT. Dairy cows, mastitis, dry-cow therapy, somatic cell count, management practices.

Self-etch and etch-and-rinse adhesive systems in clinical dentistry.

PubMed

Ozer, Fusun; Blatz, Markus B

2013-01-01

Current adhesive systems follow either an "etch-and-rinse" or "self-etch" approach, which differ in how they interact with natural tooth structures. Etch-and-rinse systems comprise phosphoric acid to pretreat the dental hard tissues before rinsing and subsequent application of an adhesive. Self-etch adhesives contain acidic monomers, which etch and prime the tooth simultaneously. Etch-and-rinse adhesives are offered as two- or three-step systems, depending on whether primer and bonding are separate or combined in a single bottle. Similarly, self-etch adhesives are available as one- or two-step systems. Both etch-and-rinse and self-etch systems form a hybrid layer as a result of resins impregnating the porous enamel or dentin. Despite current trends toward fewer and simpler clinical application steps, one-step dentin bonding systems exhibit bonding agent lower bond strengths and seem less predictable than multi-step etch-and-rinse and self-etch systems. The varying evidence available today suggests that the choice between etch-and-rinse and self-etch systems is often a matter of personal preference. In general, however, phosphoric acid creates a more pronounced and retentive etching pattern in enamel. Therefore, etch-and-rinse bonding systems are often preferred for indirect restorations and when large areas of enamel are still present. Conversely, self-etch adhesives provide superior and more predictable bond strength to dentin and are, consequently, recommended for direct composite resin restorations, especially when predominantly supported by dentin.

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells.

PubMed

Tsai, Yihuan; Cutts, Josh; Kimura, Azuma; Varun, Divya; Brafman, David A

2015-07-01

Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery. Copyright © 2015. Published by Elsevier B.V.

Biology and Biomarkers for Wound Healing

PubMed Central

Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-01-01

Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

Application of process improvement principles to increase the frequency of complete airway management documentation.

PubMed

McCarty, L Kelsey; Saddawi-Konefka, Daniel; Gargan, Lauren M; Driscoll, William D; Walsh, John L; Peterfreund, Robert A

2014-12-01

Process improvement in healthcare delivery settings can be difficult, even when there is consensus among clinicians about a clinical practice or desired outcome. Airway management is a medical intervention fundamental to the delivery of anesthesia care. Like other medical interventions, a detailed description of the management methods should be documented. Despite this expectation, airway documentation is often insufficient. The authors hypothesized that formal adoption of process improvement methods could be used to increase the rate of "complete" airway management documentation. The authors defined a set of criteria as a local practice standard of "complete" airway management documentation. The authors then employed selected process improvement methodologies over 13 months in three iterative and escalating phases to increase the percentage of records with complete documentation. The criteria were applied retrospectively to determine the baseline frequency of complete records, and prospectively to measure the impact of process improvements efforts over the three phases of implementation. Immediately before the initial intervention, a retrospective review of 23,011 general anesthesia cases over 6 months showed that 13.2% of patient records included complete documentation. At the conclusion of the 13-month improvement effort, documentation improved to a completion rate of 91.6% (P<0.0001). During the subsequent 21 months, the completion rate was sustained at an average of 90.7% (SD, 0.9%) across 82,571 general anesthetic records. Systematic application of process improvement methodologies can improve airway documentation and may be similarly effective in improving other areas of anesthesia clinical practice.

Challenges in economic modeling of anticancer therapies: an example of modeling the survival benefit of olaparib maintenance therapy for patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer.

PubMed

Hettle, Robert; Posnett, John; Borrill, John

2015-01-01

The aim of this paper is to describe a four health-state, semi-Markov model structure with health states defined by initiation of subsequent treatment, designed to make best possible use of the data available from a phase 2 clinical trial. The approach is illustrated using data from a sub-group of patients enrolled in a phase 2 clinical trial of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (NCT00753545). A semi-Markov model was developed with four health states: progression-free survival (PFS), first subsequent treatment (FST), second subsequent treatment (SST), and death. Transition probabilities were estimated by fitting survival curves to trial data for time from randomization to FST, time from FST to SST, and time from SST to death. Survival projections generated by the model are broadly consistent with the outcomes observed in the clinical trial. However, limitations of the trial data (small sample size, immaturity of the PFS and overall survival [OS] end-points, and treatment switching) create uncertainty in estimates of survival. The model framework offers a promising approach to evaluating cost-effectiveness of a maintenance therapy for patients with cancer, which may be generalizable to other chronic diseases.

Time to Send the Preemie Home? Additional Maturity at Discharge and Subsequent Health Care Costs and Outcomes

PubMed Central

Silber, Jeffrey H; Lorch, Scott A; Rosenbaum, Paul R; Medoff-Cooper, Barbara; Bakewell-Sachs, Susan; Millman, Andrea; Mi, Lanyu; Even-Shoshan, Orit; Escobar, Gabriel J

2009-01-01

Objective To determine whether longer stays of premature infants allowing for increased physical maturity result in subsequent postdischarge cost savings that help counterbalance increased inpatient costs. Data Sources One thousand four hundred and two premature infants born in the Northern California Kaiser Permanente Medical Care Program between 1998 and 2002. Study Design/Methods Using multivariate matching with a time-dependent propensity score we matched 701 “Early” babies to 701 “Late” babies (developmentally similar at the time the earlier baby was sent home but who were discharged on average 3 days later) and assessed subsequent costs and clinical outcomes. Principal Findings Late babies accrued inpatient costs after the Early baby was already home, yet costs after discharge through 6 months were virtually identical across groups, as were clinical outcomes. Overall, after the Early baby went home, the Late–Early cost difference was $5,016 (p<.0001). A sensitivity analysis suggests our conclusions would not easily be altered by failure to match on some unmeasured covariate. Conclusions In a large integrated health care system, if a baby is ready for discharge (as defined by the typical criteria), staying longer increased inpatient costs but did not reduce postdischarge costs nor improve postdischarge clinical outcomes. PMID:19207592

The development and validation of a meta-tool for quality appraisal of public health evidence: Meta Quality Appraisal Tool (MetaQAT).

PubMed

Rosella, L; Bowman, C; Pach, B; Morgan, S; Fitzpatrick, T; Goel, V

2016-07-01

Most quality appraisal tools were developed for clinical medicine and tend to be study-specific with a strong emphasis on risk of bias. In order to be more relevant to public health, an appropriate quality appraisal tool needs to be less reliant on the evidence hierarchy and consider practice applicability. Given the broad range of study designs used in public health, the objective of this study was to develop and validate a meta-tool that combines public health-focused principles of appraisal coupled with a set of design-specific companion tools. Several design methods were used to develop and validate the tool including literature review, synthesis, and validation with a reference standard. A search of critical appraisal tools relevant to public health was conducted; core concepts were collated. The resulting framework was piloted during three feedback sessions with public health practitioners. Following subsequent revisions, the final meta-tool, the Meta Quality Appraisal Tool (MetaQAT), was then validated through a content analysis of appraisals conducted by two groups of experienced public health researchers (MetaQAT vs generic appraisal form). The MetaQAT framework consists of four domains: relevancy, reliability, validity, and applicability. In addition, a companion tool was assembled from existing critical appraisal tools to provide study design-specific guidance on validity appraisal. Content analysis showed similar methodological and generalizability concerns were raised by both groups; however, the MetaQAT appraisers commented more extensively on applicability to public health practice. Critical appraisal tools designed for clinical medicine have limitations for use in the context of public health. The meta-tool structure of the MetaQAT allows for rigorous appraisal, while allowing users to simultaneously appraise the multitude of study designs relevant to public health research and assess non-standard domains, such as applicability. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exome analysis in clinical practice: expanding the phenotype of Bartsocas-Papas syndrome.

PubMed

Gripp, Karen W; Ennis, Sara; Napoli, Joseph

2013-05-01

Exome analysis has had a dramatic impact on genetic research. We present the application of such newly generated information to patient care. The patient was a female, born with normal growth parameters to nonconsanguineous parents after an uneventful pregnancy. She had bilateral cleft lip/palate and ankyloblepharon. Sparse hair, dysplastic nails and hypohidrosis were subsequently noted. With exception of speech related issues, her development was normal. A clinical diagnosis of ankyloblepharon-ectodermal defects-cleft lip/palate or Hay-Wells syndrome resulted in TP63 sequence analysis. TP63 sequence and deletion/duplication analysis of all coding exons had a normal result, as did chromosome and SNP array analysis. Diagnostic exome analysis revealed a heterozygous nonsense mutation in KRT83 categorized as deleterious and associated with monilethrix. In addition, a homozygous missense variant of unknown clinical significance was reported in RIPK4. Using research based exome analysis, RIPK4 had just a few months prior been identified as pathogenic for Bartsocas-Papas syndrome. While the clinical diagnostic report implied the KRT83 mutation as a more likely cause for the patient's phenotype, clinical correlation, literature review and use of computerized mutation analysis programs allowed us to identify the homozygous RIPK4 (c.488G > A; p.Gly163Asp) mutation as the underlying pathogenic change. Consequently, we expand the phenotype of Bartsocas-Papas syndrome to an attenuated presentation resembling Hay-Wells syndrome, lacking lethality and pterygia. In contrast to the autosomal dominant Hay-Wells syndrome, Bartsocas-Papas syndrome is autosomal recessive, implying a 25% recurrence risk. Copyright © 2013 Wiley Periodicals, Inc.

Diagnostic Performance of Electronic Syndromic Surveillance Systems in Acute Care

PubMed Central

Kashiouris, M.; O’Horo, J.C.; Pickering, B.W.; Herasevich, V.

2013-01-01

Context Healthcare Electronic Syndromic Surveillance (ESS) is the systematic collection, analysis and interpretation of ongoing clinical data with subsequent dissemination of results, which aid clinical decision-making. Objective To evaluate, classify and analyze the diagnostic performance, strengths and limitations of existing acute care ESS systems. Data Sources All available to us studies in Ovid MEDLINE, Ovid EMBASE, CINAHL and Scopus databases, from as early as January 1972 through the first week of September 2012. Study Selection: Prospective and retrospective trials, examining the diagnostic performance of inpatient ESS and providing objective diagnostic data including sensitivity, specificity, positive and negative predictive values. Data Extraction Two independent reviewers extracted diagnostic performance data on ESS systems, including clinical area, number of decision points, sensitivity and specificity. Positive and negative likelihood ratios were calculated for each healthcare ESS system. A likelihood matrix summarizing the various ESS systems performance was created. Results The described search strategy yielded 1639 articles. Of these, 1497 were excluded on abstract information. After full text review, abstraction and arbitration with a third reviewer, 33 studies met inclusion criteria, reporting 102,611 ESS decision points. The yielded I2 was high (98.8%), precluding meta-analysis. Performance was variable, with sensitivities ranging from 21% –100% and specificities ranging from 5%-100%. Conclusions There is significant heterogeneity in the diagnostic performance of the available ESS implements in acute care, stemming from the wide spectrum of different clinical entities and ESS systems. Based on the results, we introduce a conceptual framework using a likelihood ratio matrix for evaluation and meaningful application of future, frontline clinical decision support systems. PMID:23874359

START: an advanced radiation therapy information system.

PubMed

Cocco, A; Valentini, V; Balducci, M; Mantello, G

1996-01-01

START is an advanced radiation therapy information system (RTIS) which connects direct information technology present in the devices with indirect information technology for clinical, administrative, information management integrated with the hospital information system (HIS). The following objectives are pursued: to support decision making in treatment planning and functional and information integration with the rest of the hospital; to enhance organizational efficiency of a Radiation Therapy Department; to facilitate the statistical evaluation of clinical data and managerial performance assessment; to ensure the safety and confidentiality of used data. For its development a working method based on the involvement of all operators of the Radiation Therapy Department, was applied. Its introduction in the work activity was gradual, trying to reuse and integrate the existing information applications. The START information flow identifies four major phases: admission, visit of admission, planning, therapy. The system main functionalities available to the radiotherapist are: clinical history/medical report linking function; folder function; planning function; tracking function; electronic mail and banner function; statistical function; management function. Functions available to the radiotherapy technician are: the room daily list function; management function: to the nurse the following functions are available: patient directing function; management function. START is a departmental client (pc-windows)-server (unix) developed on an integrated database of all information of interest (clinical, organizational and administrative) coherent with the standard and with a modular architecture which can evolve with additional functionalities in subsequent times. For a more thorough evaluation of its impact on the daily activity of a radiation therapy facility, a prolonged clinical validation is in progress.

Development and validation of LC-MS/MS assay for the simultaneous determination of methotrexate, 6-mercaptopurine and its active metabolite 6-thioguanine in plasma of children with acute lymphoblastic leukemia: Correlation with genetic polymorphism.

PubMed

Al-Ghobashy, Medhat A; Hassan, Said A; Abdelaziz, Doaa H; Elhosseiny, Noha M; Sabry, Nirmeen A; Attia, Ahmed S; El-Sayed, Manal H

2016-12-01

Individualized therapy is a recent approach aiming to specify dosage regimen for each patient according to its genetic state. Cancer chemotherapy requires continuous monitoring of the plasma concentration levels of active forms of cytotoxic drugs and subsequent dose adjustment. In order to attain optimum therapeutic efficacy, correlation to pharmacogenetics data is crucial. In this study, a specific, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for determination of methotrexate (MTX), 6-mercaptopurine (MP) and its metabolite 6-thioguanine nucleotide (TG) in human plasma. Based on the basic character of the studied compounds, solid phase extraction using a strong cation exchanger was found the optimum approach to achieve good extraction recovery. Chromatographic separation was carried out using RP-HPLC and isocratic elution by acetonitrile: 0.1% aqueous formic acid (85:15v/v) with a flow rate of 0.8mL/min at 40°C. The detection was performed by tandem mass spectrometry in MRM mode via electrospray ionization source in positive ionization mode. Analysis was carried out within 1.0min over a concentration range of 6.25-200.00ng/mL for the studied analytes. Validation was carried out according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the monitoring of the MTX, MP and TG and subsequent application to personalized therapy was demonstrated in a clinical study on children with acute lymphoblastic leukemia (ALL). Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment. Copyright © 2016 Elsevier B.V. All rights reserved.

Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system

PubMed Central

Terslev, Lene; Naredo, Esperanza; Aegerter, Philippe; Wakefield, Richard J; Backhaus, Marina; Balint, Peter; Bruyn, George A W; Iagnocco, Annamaria; Jousse-Joulin, Sandrine; Schmidt, Wolfgang A; Szkudlarek, Marcin; Conaghan, Philip G; Filippucci, Emilio

2017-01-01

Objectives To test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms–Outcomes Measures in Rheumatology (EULAR-OMERACT) combined score for PD and SH. Methods A stepwise approach was used: (1) scoring static images of metacarpophalangeal (MCP) joints in a web-based exercise and subsequently when scanning patients; (2) scoring static images of wrist, proximal interphalangeal joints, knee and metatarsophalangeal joints in a web-based exercise and subsequently when scanning patients using different acquisitions (standardised vs usual practice). For reliability, kappa coefficients (κ) were used. Results Scoring MCP joints in static images showed substantial intraobserver variability but good to excellent interobserver reliability. In patients, intraobserver reliability was the same for the two acquisition methods. Interobserver reliability for SH (κ=0.87) and PD (κ=0.79) and the EULAR-OMERACT combined score (κ=0.86) were better when using a ‘standardised’ scan. For the other joints, the intraobserver reliability was excellent in static images for all scores (κ=0.8–0.97) and the interobserver reliability marginally lower. When using standardised scanning in patients, the intraobserver was good (κ=0.64 for SH and the EULAR-OMERACT combined score, 0.66 for PD) and the interobserver reliability was also good especially for PD (κ range=0.41–0.92). Conclusion The EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardised scan and is equally applicable in non-MCP joints. This scoring system should underpin improved reliability and consequently the responsiveness of US in RA clinical trials. PMID:28948984

Comparison between different interdental stripping methods and evaluation of abrasive strips: SEM analysis.

PubMed

Grippaudo, Cristina; Cancellieri, Daniela; Grecolini, Maria E; Deli, Roberto

2010-01-01

The aim of this study was to evaluate the morphological effects and the surface irregularities produced by different methods of mechanical stripping (abrasive strips and burs) and chemical stripping (37% orthophosphoric acid) and the surface changes following the finishing procedures (polishing strips) or the subsequent application of sealants, in order to establish the right stripping method that can guarantee the smoothest surface. We have also analysed the level of wear on the different abrasive strips employed, according to their structure. 160 proximal surfaces of 80 sound molar teeth extracted for orthodontic and periodontal reasons, were divided into: 1 control group with non-treated enamel proximal surfaces and 5 different groups according to the stripping method used, were observed with scanning electron microscopy (SEM). Each one of the 5 treated groups was also divided into 3 different subgroups according to the finishing procedures or the subsequent application of sealants. The finishing stage following the manual reduction proves to be fundamental in reducing the number and depth of grooves created by the stripping. After the air rotor stripping method, the use of sealants is advised in order to obtain a smoother surface. The analysis of the combinations of mechanical and chemical stripping showed unsatisfactory results. Concerning the wear of the strips, we have highlighted a different abrasion degree for the different types of strips analysed with SEM. The enamel damages are limited only if the finishing procedure is applied, independently of the type of abrasive strip employed. It would be advisable, though clinically seldom possible, the use of sealants after the air rotor stripping technique. Copyright © 2010 Società Italiana di Ortodonzia SIDO. Published by Elsevier Srl. All rights reserved.

Clinical trials: understanding and perceptions of female Chinese-American cancer patients.

PubMed

Tu, Shin-Ping; Chen, Hueifang; Chen, Anthony; Lim, Jeanette; May, Suepattra; Drescher, Charles

2005-12-15

Under-representation of minority and female participants prompted the U.S. legislature to mandate the inclusion of women and minorities in federally funded research. Recruitment of minorities to participate in clinical trials continues to be challenging. Although Asian Americans constitute one of the major minority groups in the U.S., published literature contains sparse data concerning the participation of Asian Americans in cancer clinical trials. The authors completed qualitative, semistructured interviews with 34 participants: Chinese-American female cancer patients ages 20-85 years or their family members. Interviews were conducted in Cantonese, Mandarin, or English and were audiotaped. Chinese interviews were translated into English, and all interviews were transcribed subsequently into English. A team of five coders individually reviewed then met to discuss the English transcripts. The authors used the constant comparative technique throughout the entire coding process as part of the analysis. Among participants, 62% lacked any knowledge of clinical trials, and many expressed negative attitudes toward clinical trials. Barriers to participation included inadequate resources, language issues, and a lack of financial and social support. Facilitating factors included recommendations by a trusted oncologist or another trusted individual and information in the appropriate language. It is noteworthy that family members played an important role in the cancer experience of these participants. To promote participation, there is a need to increase knowledge of clinical trials among Chinese cancer patients. It also is necessary to examine the applicability of current patient-physician communication and interaction models. In addition, decision-making based on Asian philosophies within the context of Euro-American bioethics requires further study. Cancer 2005. (c) 2005 American Cancer Society.

Preclinical Studies for Cartilage Repair

PubMed Central

Hurtig, Mark B.; Buschmann, Michael D.; Fortier, Lisa A.; Hoemann, Caroline D.; Hunziker, Ernst B.; Jurvelin, Jukka S.; Mainil-Varlet, Pierre; McIlwraith, C. Wayne; Sah, Robert L.; Whiteside, Robert A.

2011-01-01

Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures. PMID:26069576

Lithium Clinics in Berlin and Dresden: a 50-Year Experience.

PubMed

Felber, Werner; Bauer, Michael; Lewitzka, Ute; Müller-Oerlinghausen, Bruno

2018-06-14

Although lithium's serendipitous discovery as a medication for depression dates back more than 200 years, the first scientific evidence that it prevents mania and depression arose only in the 1960s. However, at that time there was a lack of knowledge about how to administer and monitor lithium therapy safely and properly. The lithium clinics in Dresden and Berlin were remarkably similar in their beginnings in the late 1960s regarding patient numbers and scientific expertise without being aware of one another due to the Iron Curtain separating Germany into a western and eastern part until 1990. In what were initially lithium-care programs run independently from one another, the lithium clinics embedded in academic settings in Dresden and Berlin represent a milestone in the history of psychopharmacological treatment of affective disorders in Germany and trailblazers for today's lithium therapy. Nowadays, lithium's clinical applications are unquestioned, such as its use in strategies to prevent mood episodes and suicide, and to treat depression. The extensively documented knowledge of lithium treatment is the fruit of more than 50 years of observing disease courses and of studying side effects and influencing factors of lithium prophylaxis. Its safe and proper administration-in determining the correct indication, baseline and follow-up examinations, recommended dosages, monitoring, or the management of side effects-is well established. Subsequently, both national and international guidelines continue recommending lithium as the gold standard in treating patients with unipolar and bipolar disorders. © Georg Thieme Verlag KG Stuttgart · New York.

Alternative funding for academic medicine: experience at a Canadian Health Sciences Center.

PubMed

Rosenbaum, Paul; Shortt, S E D; Walker, D M C

2004-03-01

In 1994 the School of Medicine of Queen's University in Kingston, Ontario, its clinical teachers, and the three principal teaching hospitals initiated a new approach to funding, the Alternative Funding Plan, a pragmatic response to the inability of fee-for-service billing by clinical faculty to subsidize the academic mission of the health sciences center. The center was funded to provide a package of service and academic deliverables (outputs), rather than on the basis of payment for physician clinical activity (inputs). The new plan required a new governance structure representing stakeholders and raised a number of important issues: how to reconcile the preservation of physician professional autonomy with corporate responsibilities; how to gather requisite information so as to equitably allocate resources; and how to report to the Ontario Ministry of Health and Long-term Care in order to demonstrate accountability. In subsequent iterations of the agreement it was necessary to address issues of flexibility resulting from locked-in funding levels and to devise meaningful performance measures for departments and the center as a whole. The authors conclude that the Alternative Funding Plan represents a successful innovation in funding for an academic health sciences center in that it has created financial stability, as well as modest positive effects for education and research. The Ontario government hopes to replicate the model at the province's other four health sciences centers, and it may have applicability in any jurisdiction in which the costs of medical education outstrip the capacity of faculty clinical earnings.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Caries prevention through the fluoridation of milk. A review.

PubMed

Bánóczy, Jolán; Rugg-Gunn, Andrew J

2007-10-01

The aim of this review is to give an overview of 50 years experience of milk fluoridation and draw conclusions about the applicability of the method. Fluoridated milk was first investigated in the early 1950s, almost simultaneously in Switzerland, the USA and Japan. Stimulated by the favourable results obtained from these early studies, the establishment of The Borrow Dental Milk Foundation (subsequently The Borrow Foundation) in England gave an excellent opportunity for further research, both clinical and non-clinical, and a productive collaboration with the World Health Organization from the early 1980s onwards. Numerous peer-reviewed publications in international journals showed clearly the bioavailability of fluoride in milk, and increased concentrations of fluoride in saliva, dental plaque, dental enamel and dentine, and urine, after consumption of fluoridated milk. Clinical trials were initiated in the 1980s--some of these can be classed as randomised controlled trials, while most of the clinical studies were community preventive programs. These evaluations showed clearly that the optimal daily intake of fluoride in milk is effective in preventing dental caries. At present, milk fluoridation programs are running continuously in about ten countries of the world. Fluoridation of milk can be recommended as a caries preventive measure where the fluoride concentration in drinking water is suboptimal, caries experience in children is significant, and there is an existing school milk program. The program should aim to provide fluoridated milk for at least 200 days per year and should commence before the children are 4 years of age.

40 CFR 417.20 - Applicability; description of the fatty acid manufacturing by fat splitting subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... POINT SOURCE CATEGORY Fatty Acid Manufacturing by Fat Splitting Subcategory § 417.20 Applicability; description of the fatty acid manufacturing by fat splitting subcategory. The provisions of this subpart are applicable to discharges resulting from the splitting of fats to fatty acids by hydrolysis and the subsequent...

78 FR 24395 - Applications for New Awards; Training and Information for Parents of Children With Disabilities...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... DEPARTMENT OF EDUCATION Applications for New Awards; Training and Information for Parents of... applications for new awards for fiscal year (FY) 2013. Catalog of Federal Domestic Assistance (CFDA) Number: 84... Individuals with Disabilities Education Act (IDEA)). Absolute Priority: For FY 2013 and any subsequent year in...

Estrogen transport in surface runoff from agricultural fields treated with two different application methods of dairy manure

USDA-ARS?s Scientific Manuscript database

While the land-application of animal manure provides many benefits, concerns exist regarding the subsequent transport of hormones and potential effects on aquatic ecosystems. This study compares two methods of dairy manure application, surface broadcasting and shallow disk injection, on the fate and...

40 CFR 417.20 - Applicability; description of the fatty acid manufacturing by fat splitting subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POINT SOURCE CATEGORY Fatty Acid Manufacturing by Fat Splitting Subcategory § 417.20 Applicability; description of the fatty acid manufacturing by fat splitting subcategory. The provisions of this subpart are applicable to discharges resulting from the splitting of fats to fatty acids by hydrolysis and the subsequent...

6 CFR 37.11 - Application and documents the applicant must provide.

Code of Federal Regulations, 2010 CFR

2010-01-01

... subsequent visits. (c) Identity. (1) To establish identity, the applicant must present at least one of the... present at least one document included in paragraph (c) of this section. (e) Social security number (SSN). (1) Except as provided in paragraph (e)(3) of this section, individuals presenting the identity...

Treatment of femoro-popliteal lesions with scoring and drug-coated balloon angioplasty: 12-month results of the DCB-Trak registry.

PubMed

Baumhäkel, Magnus; Chkhetia, Shalva; Kindermann, Michael

2018-01-01

Debulking strategies prior to drug-coated balloon (DCB) angioplasty were suggested to improve clinical results in femoro-popliteal lesions. Currently, there are no data regarding plaque modification with a scoring balloon with subsequent DCB-angioplasty. Recently published 6-month results of the DCB-Trak registry in patients treated with scoring-balloon angioplasty and DCB-angioplasty were promising without any safety concerns. Herein, we report the 12-month follow-up data. In a single center registry, 29 consecutive patients with 32 femoro-popliteal lesions were treated with a scoring-balloon (VascuTrak®) and a DCB subsequently. The primary endpoint was the clinically driven target lesion revascularization (TLR). Secondary endpoints were clinically driven target vessel revascularization (TVR), binary restenosis (peak systolic velocity ratio > 2.4), change in Rutherford classification and ankle-brachial-index (ABI). Safety endpoints were major cardiovascular events (cardiovascular death, myocardial infarction, stroke, death) and need for amputation. The procedure was successful in 29 lesions. There were no clinically driven TLRs after 12 months. Two patients required clinically driven TVR and one patient had a binary restenosis. ABI significantly increased after the procedure (0.87±0.24 to 1.04±0.18, P < 0.01) without a relevant change after 6 months (1.01±0.15, P < 0.05) or 12 months (1.01±0.20, P < 0.05). Rutherford classification improved in more than 90% of patients after 6 and 12 months. There was one major cardiovascular event at 6-month follow-up, but no amputations at 6- or 12-month follow-up. Vessel preparation with a scoring-balloon and subsequent DCB-angioplasty was safe and effective in patients with femoro-popliteal lesions. Further multicenter trials have to validate these results.

Analysis of appropriateness of outpatient CT and MRI referred from primary care clinics at an academic medical center: how critical is the need for improved decision support?

PubMed

Lehnert, Bruce E; Bree, Robert L

2010-03-01

The aim of this study was to retrospectively analyze a large group of CT and MRI examinations for appropriateness using evidence-based guidelines. The authors reviewed medical records from 459 elective outpatient CT and MR examinations from primary care physicians. Evidence-based appropriateness criteria from a radiology benefit management company were used to determine if the examination would have met criteria for approval. Submitted clinical history at the time of interpretation and clinic notes and laboratory results preceding the date of the imaging study were examined to simulate a real-time consultation with the referring provider. The radiology reports and subsequent clinic visits were analyzed for outcomes. Of the 459 examinations reviewed, 284 (62%) were CT and 175 (38%) were MRI. Three hundred forty-one (74%) were considered appropriate, and 118 (26%) were not considered appropriate. Examples of inappropriate examinations included brain CT for chronic headache, lumbar spine MR for acute back pain, knee or shoulder MRI in patients with osteoarthritis, and CT for hematuria during a urinary tract infection. Fifty-eight percent of the appropriate studies had positive results and affected subsequent management, whereas only thirteen percent [corrected] of inappropriate studies had positive results and affected management. A high percentage of examinations not meeting appropriateness criteria and subsequently yielding negative results suggests a need for tools to help primary care physicians improve the quality of their imaging decision requests. In the current environment, which stresses cost containment and comparative effectiveness, traditional radiology benefit management tools are being challenged by clinical decision support, with an emphasis on provider education coupled with electronic order entry systems.

Endodontic applications of a short pulsed FR Nd:YAG dental laser: photovaporization of extruded pulpal tissue following traumatic fractures of two maxillary central incisors--a clinical trial repor

NASA Astrophysics Data System (ADS)

Gregg, Robert H., II

1992-06-01

Historically, many techniques have been attempted in the search for a satisfactory and consistent treatment of inflamed, painful, hyperemic pulpal tissue. Present techniques attempting to achieve profound local anesthesia in such tissue, have not been satisfactory. Local anesthesia techniques acceptable to the patient with painful hyperemic pulpal tissue, has eluded previous technology. The subsequent treatment of hyperemic tissue without sufficient anesthesia primarily involves undesirable invasive mechanical/surgical procedures. Described in this clinical trial is a technique using free running (FR) pulsed, Nd:YAG laser energy to ablate soft tooth pulpal tissue--a technique employed after conventional endodontic methods failed. A free running pulsed, FR Nd:YAG dental laser was successfully used at 20 pulses per second and 1.25 watts to photovaporize endodontic pulpal tissue (pulpectomy) to allow a conventional endodontic file to extirpate the remaining soft tissue remnants and access the root apex. Also described in this paper is the 'hot-tip' effect of contact fiber laser surgery. This clinical trial achieved the immediate, short term objective of endodontic soft tissue removal via photovaporization, without pain reported by the patient. The pulsed FR Nd:YAG dental laser used as described in this clinical report appears to be a very safe and very effective technique; offers a treatment alternative to traditional therapy that suggests high patient acceptance; and is significantly less stressful for the doctor and staff than traditional treatment options. Long-term, controlled scientific and clinical studies are necessary to establish the safety and efficacy of both the helium-neon energy for visualization and the low-watt pulsed FR Nd:YAG energy for photovaporization of soft endodontic pulpal tissue within the root canal. Research is especially needed to understand the effects of a low-watt, pulsed FR, Nd:YAG laser on the activity of osteoclasts and odontoclasts and identify risks for developing external and/or internal resorption after intracanal application of pulsed FR Nd:YAG laser energy.

The role of clinician emotion in clinical reasoning: Balancing the analytical process.

PubMed

Langridge, Neil; Roberts, Lisa; Pope, Catherine

2016-02-01

This review paper identifies and describes the role of clinicians' memory, emotions and physical responses in clinical reasoning processes. Clinical reasoning is complex and multi-factorial and key models of clinical reasoning within musculoskeletal physiotherapy are discussed, highlighting the omission of emotion and subsequent physical responses and how these can impact upon a clinician when making a decision. It is proposed that clinicians should consider the emotions associated with decision-making, especially when there is concern surrounding a presentation. Reflecting on practice in the clinical environment and subsequently applying this to a patient presentation should involve some acknowledgement of clinicians' physical responses, emotions and how they may play a part in any decision made. Presenting intuition and gut-feeling as separate reasoning methods and how these processes co-exist with other more accepted reasoning such as hypothetico-deductive is also discussed. Musculoskeletal physiotherapy should consider the elements of feelings, emotions and physical responses when applying reflective practice principles. Furthermore, clinicians dealing with difficult and challenging presentations should look at the emotional as well as the analytical experience when justifying decisions and learning from practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer Vaccines: Moving Beyond Current Paradigms

PubMed Central

Schlom, Jeffrey; Arlen, Philip M.; Gulley, James L.

2008-01-01

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. While no therapeutic cancer vaccine has to date been approved by the FDA, several new paradigms are emerging from recent clinical findings in both the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and endpoint analyses. This paper will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classical “tumor response” (RECIST) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies, and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies. PMID:17606707

High-throughput, fully-automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment

PubMed Central

Kovacevic, Sanja; Rafii, Michael S.; Brewer, James B.

2008-01-01

Medial temporal lobe (MTL) atrophy is associated with increased risk for conversion to Alzheimer's disease (AD), but manual tracing techniques and even semi-automated techniques for volumetric assessment are not practical in the clinical setting. In addition, most studies that examined MTL atrophy in AD have focused only on the hippocampus. It is unknown the extent to which volumes of amygdala and temporal horn of the lateral ventricle predict subsequent clinical decline. This study examined whether measures of hippocampus, amygdala, and temporal horn volume predict clinical decline over the following 6-month period in patients with mild cognitive impairment (MCI). Fully-automated volume measurements were performed in 269 MCI patients. Baseline volumes of the hippocampus, amygdala, and temporal horn were evaluated as predictors of change in Mini-mental State Exam (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR SB) over a 6-month interval. Fully-automated measurements of baseline hippocampus and amygdala volumes correlated with baseline delayed recall scores. Patients with smaller baseline volumes of the hippocampus and amygdala or larger baseline volumes of the temporal horn had more rapid subsequent clinical decline on MMSE and CDR SB. Fully-automated and rapid measurement of segmental MTL volumes may help clinicians predict clinical decline in MCI patients. PMID:19474571

Evaluation of the Use of a Virtual Patient on Student Competence and Confidence in Performing Simulated Clinic Visits.

PubMed

Taglieri, Catherine A; Crosby, Steven J; Zimmerman, Kristin; Schneider, Tulip; Patel, Dhiren K

2017-06-01

Objective. To assess the effect of incorporating virtual patient activities in a pharmacy skills lab on student competence and confidence when conducting real-time comprehensive clinic visits with mock patients. Methods. Students were randomly assigned to a control or intervention group. The control group completed the clinic visit prior to completing virtual patient activities. The intervention group completed the virtual patient activities prior to the clinic visit. Student proficiency was evaluated in the mock lab. All students completed additional exercises with the virtual patient and were subsequently assessed. Student impressions were assessed via a pre- and post-experience survey. Results. Student performance conducting clinic visits was higher in the intervention group compared to the control group. Overall student performance continued to improve in the subsequent module. There was no change in student confidence from pre- to post-experience. Student rating of the ease of use and realistic simulation of the virtual patient increased; however, student rating of the helpfulness of the virtual patient decreased. Despite student rating of the helpfulness of the virtual patient program, student performance improved. Conclusion. Virtual patient activities enhanced student performance during mock clinic visits. Students felt the virtual patient realistically simulated a real patient. Virtual patients may provide additional learning opportunities for students.

Successful Application of Adaptive Emotion Regulation Skills Predicts the Subsequent Reduction of Depressive Symptom Severity but neither the Reduction of Anxiety nor the Reduction of General Distress during the Treatment of Major Depressive Disorder

PubMed Central

Wirtz, Carolin M.; Radkovsky, Anna; Ebert, David D.; Berking, Matthias

2014-01-01

Objective Deficits in general emotion regulation (ER) skills have been linked to symptoms of depression and are thus considered a promising target in the treatment of Major depressive disorder (MDD). However, at this point, the extent to which such skills are relevant for coping with depression and whether they should instead be considered a transdiagnostic factor remain unclear. Therefore, the present study aimed to investigate whether successful ER skills application is associated with changes in depressive symptom severity (DSS), anxiety symptom severity (ASS), and general distress severity (GDS) over the course of treatment for MDD. Methods Successful ER skills application, DSS, ASS, and GDS were assessed four times during the first three weeks of treatment in 175 inpatients who met the criteria for MDD. We computed Pearson correlations to test whether successful ER skills application and the three indicators of psychopathology are cross-sectionally associated. We then performed latent growth curve modelling to test whether changes in successful ER skills application are negatively associated with a reduction of DSS, ASS, or GDS. Finally, we utilized latent change score models to examine whether successful ER skills application predicts subsequent reduction of DSS, ASS, or GDS. Results Successful ER skills application was cross-sectionally associated with lower levels of DSS, ASS, and GDS at all points of assessment. An increase in successful skills application during treatment was associated with a decrease in DSS and GDS but not ASS. Finally, successful ER skills application predicted changes in subsequent DSS but neither changes in ASS nor changes in GDS. Conclusions Although general ER skills might be relevant for a broad range of psychopathological symptoms, they might be particularly important for the maintenance and treatment of depressive symptoms. PMID:25330159

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0.51-0.83)). Conclusion A total of 15% of pulmonary clinical highly likely applicable clinical trials report basic summary results to ClinicalTrials.gov within 1 year of trial completion. Strategies to improve reporting are needed within the pulmonary community.

Learning of Musculoskeletal Ligament Stress Testing in a Gross Anatomy Laboratory

ERIC Educational Resources Information Center

Krause, David A.; Youdas, James W.; Hollman, John H.

2011-01-01

Human anatomy in physical therapy programs is a basic science course serving as a foundation for subsequent clinical courses. Integration of anatomy with a clinical emphasis throughout a curriculum provides opportunities for reinforcement of previously learned material. Considering the human cadaver laboratory as a fixed cost to our program, we…

Bronchogenic cyst presenting as a symptomatic neck mass in an adult: case report and review of the literature.

PubMed

Al-kasspooles, Mazin F; Alberico, Ronald A; Douglas, Wade G; Litwin, Alan M; Wiseman, Sam M; Rigual, Nestor R; Loree, Thom R; Hicks, Wesley L

2004-12-01

We report the unusual clinical manifestation and subsequent management of a symptomatic congenital bronchogenic cyst that connected to the trachea and presented in the neck of an adult. The embryology, clinical presentation, diagnostic evaluation, and management options of this rare aberration are discussed.

Does My Program Really Make a Difference? Program Evaluation Utilizing Aggregate Single-Subject Data

ERIC Educational Resources Information Center

Burns, Catherine E.

2015-01-01

In the current climate of increasing fiscal and clinical accountability, information is required about overall program effectiveness using clinical data. These requests present a challenge for programs utilizing single-subject data due to the use of highly individualized behavior plans and behavioral monitoring. Subsequently, the diversity of the…

The effect of tilmicosin administered to ewes prior to lambing on incidence of clinical mastitis and subsequent lamb performance.

PubMed Central

Croft, A; Duffield, T; Menzies, P; Leslie, K; Bagg, R; Dick, P

2000-01-01

The effect of tilmicosin on the incidence of clinical mastitis and subsequent lamb performance was studied in 9 sheep flocks in Ontario. Ewes were treated randomly with either tilmicosin or placebo approximately one month prior to lambing. Outcome was assessed by comparing rates of clinical mastitis, palpable udder abnormalities, and preweaning (50-day) lamb weights between the 2 treatment groups, while controlling for other important variables. Lambs raised by multiparous ewes treated with tilmicosin were significantly heavier than lambs from placebo-treated multiparous ewes at 50 days. Lambs from tilmicosin-treated ewes were on average 0.52 kg heavier than lambs in the placebo group. There was no difference between treatment groups in the weight of lambs from first parity ewes. Tilmicosin treatment resulted in a 43% decrease in palpable udder abnormalities. Incidence of clinical mastitis did not differ between experimental groups. The administration of tilmicosin prelambing, at the time of routine clostridial disease vaccination, may be a beneficial and convenient way to reduce mastitis infection and improve the preweaning gain of lambs. PMID:10769768

Effects of Noncontingent Social Interaction on Immediate and Subsequent Engagement in Vocal and Motor Stereotypy in Children With Autism.

PubMed

Enloe, Kimberley A; Rapp, John T

2014-05-01

This study evaluated the effects of noncontingent social interaction (SI) on immediate and subsequent engagement in vocal and motor stereotypy in three children with autism. During SI, a therapist delivered continuous interaction in the form of reading aloud from a Kindle™ e-reader. Results showed that when compared with a no-interaction baseline sequence, SI decreased immediate engagement vocal stereotypy for all three participants without increasing subsequent engagement for any participant. Furthermore, SI also increased immediate engagement in motor stereotypy for one participant, decreased immediate engagement in motor stereotypy for two participants, but did not increase subsequent engagement in motor stereotypy for any participant. Some clinical implications and limitations of the findings are discussed. © The Author(s) 2013.

26 CFR 1.401(a)-20 - Requirements of qualified joint and survivor annuity and qualified preretirement survivor annuity.

Code of Federal Regulations, 2012 CFR

2012-04-01

... calculated using the applicable interest rate (and, for periods when required, the applicable mortality table... before the annuity starting date paid to A's children, A may not subsequently change beneficiaries...

26 CFR 1.401(a)-20 - Requirements of qualified joint and survivor annuity and qualified preretirement survivor annuity.

Code of Federal Regulations, 2013 CFR

2013-04-01

... calculated using the applicable interest rate (and, for periods when required, the applicable mortality table... before the annuity starting date paid to A's children, A may not subsequently change beneficiaries...

26 CFR 1.401(a)-20 - Requirements of qualified joint and survivor annuity and qualified preretirement survivor annuity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... calculated using the applicable interest rate (and, for periods when required, the applicable mortality table... before the annuity starting date paid to A's children, A may not subsequently change beneficiaries...

26 CFR 1.401(a)-20 - Requirements of qualified joint and survivor annuity and qualified preretirement survivor annuity.

Code of Federal Regulations, 2014 CFR

2014-04-01

... calculated using the applicable interest rate (and, for periods when required, the applicable mortality table... before the annuity starting date paid to A's children, A may not subsequently change beneficiaries...

Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience.

PubMed

Knepper, Todd C; Bell, Gillian C; Hicks, J Kevin; Padron, Eric; Teer, Jamie K; Vo, Teresa T; Gillis, Nancy K; Mason, Neil T; McLeod, Howard L; Walko, Christine M

2017-02-01

The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice. In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine. Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting-edge practice merged with individualized preferences in treatment and care. Genomic-driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence-based translation of observed molecular alterations into patient-centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. The Oncologist 2017;22:144-151 Implications for Practice: It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards. © AlphaMed Press 2017.

Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience

PubMed Central

Knepper, Todd C.; Bell, Gillian C.; Hicks, J. Kevin; Padron, Eric; Teer, Jamie K.; Vo, Teresa T.; Gillis, Nancy K.; Mason, Neil T.; Walko, Christine M.

2017-01-01

Abstract Background. The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice. Materials and Methods. In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine. Results. Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting‐edge practice merged with individualized preferences in treatment and care. Conclusions. Genomic‐driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence‐based translation of observed molecular alterations into patient‐centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. Implications for Practice. It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards. PMID:28179575

What’s in a drop? Correlating observations and outcomes to guide macromolecular crystallization experiments

PubMed Central

Luft, Joseph R.; Wolfley, Jennifer R.; Snell, Edward H.

2011-01-01

Observations of crystallization experiments are classified as specific outcomes and integrated through a phase diagram to visualize solubility and thereby direct subsequent experiments. Specific examples are taken from our high-throughput crystallization laboratory which provided a broad scope of data from 20 million crystallization experiments on 12,500 different biological macromolecules. The methods and rationale are broadly and generally applicable in any crystallization laboratory. Through a combination of incomplete factorial sampling of crystallization cocktails, standard outcome classifications, visualization of outcomes as they relate chemically and application of a simple phase diagram approach we demonstrate how to logically design subsequent crystallization experiments. PMID:21643490

In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research

PubMed Central

Desmet, Eline; Ramadhas, Anesh; Lambert, Jo

2017-01-01

Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis skin or the disease pathology. This work provides a complete overview of the different available in vitro psoriasis models and suggests improvements for future models. Moreover, a focus was given to psoriatic skin equivalent models, as they offer several advantages over the other models, including commercial availability and validity. The potential and reported applicability of these models in psoriasis pre-clinical research is extensively discussed. As such, this work offers a guide to researchers in their choice of pre-clinical psoriasis model depending on their type of research question. PMID:28585891

In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research.

PubMed

Desmet, Eline; Ramadhas, Anesh; Lambert, Jo; Van Gele, Mireille

2017-06-01

Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis skin or the disease pathology. This work provides a complete overview of the different available in vitro psoriasis models and suggests improvements for future models. Moreover, a focus was given to psoriatic skin equivalent models, as they offer several advantages over the other models, including commercial availability and validity. The potential and reported applicability of these models in psoriasis pre-clinical research is extensively discussed. As such, this work offers a guide to researchers in their choice of pre-clinical psoriasis model depending on their type of research question.

20 CFR 655.750 - What is the validity period of the labor condition application?

Code of Federal Regulations, 2010 CFR

2010-04-01

... ETA 9035E or ETA 9035. The validity period of an LCA will not begin before the application is... in writing and must be sent to ETA, Office of Foreign Labor Certification. ETA will publish the... is superseded by a subsequent application which is certified by ETA. (4) An employer's obligation to...

20 CFR 416.624 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2010 CFR

2010-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews..., unless we determine, within our discretion, that a new face-to-face interview is necessary. We base this...

20 CFR 404.2024 - How do we investigate a representative payee applicant?

Code of Federal Regulations, 2010 CFR

2010-04-01

..., we do the following: (1) Conduct a face-to-face interview with the payee applicant unless it is... interviews. After holding a face-to-face interview with a payee applicant, subsequent face-to-face interviews..., unless we determine, within our discretion, that a new face-to-face interview is necessary. We base this...

7 CFR 1951.11 - Application of payments on real estate accounts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 14 2011-01-01 2011-01-01 false Application of payments on real estate accounts. 1951... Servicing Policies § 1951.11 Application of payments on real estate accounts. (a) Regular payments. If a borrower owes more than one type of real estate loan, or has received initial and subsequent real estate...

7 CFR 1951.11 - Application of payments on real estate accounts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Application of payments on real estate accounts. 1951... Servicing Policies § 1951.11 Application of payments on real estate accounts. (a) Regular payments. If a borrower owes more than one type of real estate loan, or has received initial and subsequent real estate...

7 CFR 1951.11 - Application of payments on real estate accounts.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 14 2012-01-01 2012-01-01 false Application of payments on real estate accounts. 1951... Servicing Policies § 1951.11 Application of payments on real estate accounts. (a) Regular payments. If a borrower owes more than one type of real estate loan, or has received initial and subsequent real estate...

7 CFR 1951.11 - Application of payments on real estate accounts.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 14 2013-01-01 2013-01-01 false Application of payments on real estate accounts. 1951... Servicing Policies § 1951.11 Application of payments on real estate accounts. (a) Regular payments. If a borrower owes more than one type of real estate loan, or has received initial and subsequent real estate...

7 CFR 1951.11 - Application of payments on real estate accounts.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 14 2014-01-01 2014-01-01 false Application of payments on real estate accounts. 1951... Servicing Policies § 1951.11 Application of payments on real estate accounts. (a) Regular payments. If a borrower owes more than one type of real estate loan, or has received initial and subsequent real estate...

40 CFR 63.10006 - When must I conduct subsequent performance tests or tune-ups?

Code of Federal Regulations, 2012 CFR

2012-07-01

... applicable periodic HCl emissions tests according to Table 5 to this subpart and § 63.10007 at least... performance tests according to Table 5 to this subpart and § 63.10007 at least every year. (b) For affected... years (once every year for Hg) according to Table 5 and § 63.10007. Should subsequent emissions testing...

40 CFR 63.10006 - When must I conduct subsequent performance tests or tune-ups?

Code of Federal Regulations, 2014 CFR

2014-07-01

... limit, you must conduct all applicable periodic HCl emissions tests according to Table 5 to this subpart... performance tests according to Table 5 to this subpart and § 63.10007 at least every year. (b) For affected... years (once every year for Hg) according to Table 5 and § 63.10007. Should subsequent emissions testing...

40 CFR 63.10006 - When must I conduct subsequent performance tests or tune-ups?

Code of Federal Regulations, 2013 CFR

2013-07-01

... limit, you must conduct all applicable periodic HCl emissions tests according to Table 5 to this subpart... performance tests according to Table 5 to this subpart and § 63.10007 at least every year. (b) For affected... years (once every year for Hg) according to Table 5 and § 63.10007. Should subsequent emissions testing...

Mastitis outcomes on pre-ovulatory follicle diameter, estradiol concentrations, subsequent luteal profiles and conception rate in Buffaloes.

PubMed

Mansour, Mohamed Mohsen; Zeitoun, Moustafa M; Hussein, Fekry M

2017-06-01

The objectives of this study was to investigate the outcome of mastitis, in its clinical or subclinical forms, on the mean diameter of pre-ovulatory follicle (POF), plasma estradiol concentration on the day of estrus, subsequent luteal profile and subsequent conception rate in buffaloes. Sixty dairy buffalo (Bubalus bubalus) conducted in this study were divided into three groups {healthy (H), n=20; subclinical mastitis (SCM), n=18; and clinical mastitis (CM), n=22}. Ultrasonography of ovaries revealed that mean diameter of POF was larger (P<0.05) in H buffalo (14.35mm) compared to SCM (12.40mm) and CM (10.25mm). Also, plasma estradiol concentration on the day of estrus was higher (P<0.05) in H buffalo compared to SCM and CM counterparts; 34.95 vs. 32.87 and 27.50pg/ml, respectively. Besides, positive correlation was observed between the POF diameter with plasma estradiol concentration in H, SCM and CM buffaloes (r=0.64, 0.74, 0.72 respectively, P<0.05). Moreover, positive correlations (P<0.01) were found on days 9, 12, 16, and 21 post-ovulation between POF diameter and luteal profile. Thus, the conception rate in H buffalo was higher (P<0.05) compared with SCM and CM counterparts; 55% vs. 38.89 and 18.18%, respectively. In conclusion, mastitis in its clinical or subclinical forms disrupts the functioning of the pre-ovulatory follicle on the day of estrus, associated with low follicular estradiol production, resulting in suppression to subsequent luteal profile leading to substantial decrease in pregnancy consequence of buffaloes. Copyright © 2017 Elsevier B.V. All rights reserved.

The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations

PubMed Central

Bodini, Margherita; Ronchini, Chiara; Giacò, Luciano; Russo, Anna; Melloni, Giorgio E. M.; Luzi, Lucilla; Sardella, Domenico; Volorio, Sara; Hasan, Syed K.; Ottone, Tiziana; Lavorgna, Serena; Lo-Coco, Francesco; Candoni, Anna; Fanin, Renato; Toffoletti, Eleonora; Iacobucci, Ilaria; Martinelli, Giovanni; Cignetti, Alessandro; Tarella, Corrado; Bernard, Loris; Pelicci, Pier Giuseppe

2015-01-01

The analyses carried out using 2 different bioinformatics pipelines (SomaticSniper and MuTect) on the same set of genomic data from 133 acute myeloid leukemia (AML) patients, sequenced inside the Cancer Genome Atlas project, gave discrepant results. We subsequently tested these 2 variant-calling pipelines on 20 leukemia samples from our series (19 primary AMLs and 1 secondary AML). By validating many of the predicted somatic variants (variant allele frequencies ranging from 100% to 5%), we observed significantly different calling efficiencies. In particular, despite relatively high specificity, sensitivity was poor in both pipelines resulting in a high rate of false negatives. Our findings raise the possibility that landscapes of AML genomes might be more complex than previously reported and characterized by the presence of hundreds of genes mutated at low variant allele frequency, suggesting that the application of genome sequencing to the clinic requires a careful and critical evaluation. We think that improvements in technology and workflow standardization, through the generation of clear experimental and bioinformatics guidelines, are fundamental to translate the use of next-generation sequencing from research to the clinic and to transform genomic information into better diagnosis and outcomes for the patient. PMID:25499761

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

PubMed

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-09-07

To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity

PubMed Central

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-01-01

AIM To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). RESULTS Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. CONCLUSION Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties. PMID:28970722

Study of sample preparation for determination of endocannabinoids and analogous compounds in human serum by LC-MS/MS in MRM mode.

PubMed

Luque-Córdoba, D; Calderón-Santiago, M; Luque de Castro, M D; Priego-Capote, F

2018-08-01

Endocannabinoids are lipids with a key role in physiological processes such as the immune response or the metabolism. This involvement explains their association to pathologies such as cancer, obesity or multiple sclerosis. The determination of endocannabinoids constitutes a challenge for clinical laboratories due to the variety of biological matrices and the wide range of concentrations at which they can be found. This research deals with the comparison of three sample preparation strategies (viz., on-line SPE, off-line SPE for interferents removal, and protein precipitation) for subsequent LC-MS/MS analysis of 14 endocannabinoids and analogous compounds in serum. As a result, the on-line coupling between SPE and LC-MS/MS is proposed as the best approach for this determination. The proposed method allows full automation of the overall process, shortening of the analysis time, and avoidance of errors associated with sample preparation steps. The improvement in sensitivity and selectivity thus achieved allows obtaining quantification limits at the pg mL -1 level, which makes possible the application of the method for clinical studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Discrimination and chemical characterization of different Paeonia lactifloras (Radix Paeoniae Alba and Radix Paeoniae Rubra) by infrared macro-fingerprint analysis-through-separation

NASA Astrophysics Data System (ADS)

Wang, Yang; Wang, Ping; Xu, Changhua; Sun, Suqin; Zhou, Qun; Shi, Zhe; Li, Jin; Chen, Tao; Li, Zheng; Cui, Weili

2015-11-01

Paeonia lactiflora, a commonly used herbal medicine (HM) in Traditional Chinese Medicine (TCM), mainly has two species, Radix Paeoniae Alba (RPA) and Radix Paeoniae Rubra (RPR), for different clinical applications in TCM. For expounding the chemical profile of RPA and RPR and ensuring the clinical efficacy and safety, an infrared macro-fingerprint analysis-through-separation method integrated with statistical pattern recognition was developed to analyze and discriminate the two Paeonia lactifloras. In IR spectra, the major difference between the two was in the range of 1200-900 cm-1: the strongest peak of RPA was at 1024 cm-1, while that of RPR was 1049 cm-1. The difference was magnified in second derivative spectra. The findings were further verified by investigating the separation process of total glucosides, stepwisely monitored by both of IR and UPLC-MS/MS. Simultaneously, the aqueous extracts of RPA and RPR had been separated continuously to acquire the comprehensively hierarchical chemical characteristics for undoubtedly identification and subsequently discrimination of the two herbs. Moreover, 60 batches of the two HMs (30 for each) were objectively classified by principal component regression (PCR) model based on IR macro-fingerprints.

Gold nanoparticle should understand protein corona for being a clinical nanomaterial.

PubMed

Charbgoo, Fahimeh; Nejabat, Mojgan; Abnous, Khalil; Soltani, Fatemeh; Taghdisi, Seyed Mohammad; Alibolandi, Mona; Thomas Shier, W; Steele, Terry W J; Ramezani, Mohammad

2018-02-28

Gold nanoparticles (AuNPs) have attracted great attention in biomedical fields due to their unique properties. However, there are few reports on clinical trial of these nanoparticles. In vivo, AuNPs face complex biological fluids containing abundant proteins, which challenge the prediction of their fate that is known as "bio-identity". These proteins attach onto the AuNPs surface forming protein corona that makes the first step of nano-bio interface and dictates the subsequent AuNPs fate. Protein corona formation even stealth active targeting effect of AuNPs. Manipulating the protein corona identity based on the researcher goal is the way to employ corona to achieve maximum effect in therapy or other applications. In this review, we provide details on the biological identity of AuNPs under various environmental- and/or physiological conditions. We also highlight how the particular corona can direct the biodistribution of AuNPs. We further discuss the strategies available for controlling or reducing corona formation on AuNPs surface and achieving desired effects using AuNPs in vivo by engineering protein corona on their surface. Copyright © 2018 Elsevier B.V. All rights reserved.

Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags

PubMed Central

Wee, Eugene J.H.; Wang, Yuling; Tsao, Simon Chang-Hao; Trau, Matt

2016-01-01

Sensitive and accurate identification of specific DNA mutations can influence clinical decisions. However accurate diagnosis from limiting samples such as circulating tumour DNA (ctDNA) is challenging. Current approaches based on fluorescence such as quantitative PCR (qPCR) and more recently, droplet digital PCR (ddPCR) have limitations in multiplex detection, sensitivity and the need for expensive specialized equipment. Herein we describe an assay capitalizing on the multiplexing and sensitivity benefits of surface-enhanced Raman spectroscopy (SERS) with the simplicity of standard PCR to address the limitations of current approaches. This proof-of-concept method could reproducibly detect as few as 0.1% (10 copies, CV < 9%) of target sequences thus demonstrating the high sensitivity of the method. The method was then applied to specifically detect three important melanoma mutations in multiplex. Finally, the PCR/SERS assay was used to genotype cell lines and ctDNA from serum samples where results subsequently validated with ddPCR. With ddPCR-like sensitivity and accuracy yet at the convenience of standard PCR, we believe this multiplex PCR/SERS method could find wide applications in both diagnostics and research. PMID:27446486

Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags.

PubMed

Wee, Eugene J H; Wang, Yuling; Tsao, Simon Chang-Hao; Trau, Matt

2016-01-01

Sensitive and accurate identification of specific DNA mutations can influence clinical decisions. However accurate diagnosis from limiting samples such as circulating tumour DNA (ctDNA) is challenging. Current approaches based on fluorescence such as quantitative PCR (qPCR) and more recently, droplet digital PCR (ddPCR) have limitations in multiplex detection, sensitivity and the need for expensive specialized equipment. Herein we describe an assay capitalizing on the multiplexing and sensitivity benefits of surface-enhanced Raman spectroscopy (SERS) with the simplicity of standard PCR to address the limitations of current approaches. This proof-of-concept method could reproducibly detect as few as 0.1% (10 copies, CV < 9%) of target sequences thus demonstrating the high sensitivity of the method. The method was then applied to specifically detect three important melanoma mutations in multiplex. Finally, the PCR/SERS assay was used to genotype cell lines and ctDNA from serum samples where results subsequently validated with ddPCR. With ddPCR-like sensitivity and accuracy yet at the convenience of standard PCR, we believe this multiplex PCR/SERS method could find wide applications in both diagnostics and research.

Stem Cells as a Tool for Breast Imaging

PubMed Central

Padín-Iruegas, Maria Elena; López López, Rafael

2012-01-01

Stem cells are a scientific field of interest due to their therapeutic potential. There are different groups, depending on the differentiation state. We can find lonely stem cells, but generally they distribute in niches. Stem cells don't survive forever. They are affected for senescence. Cancer stem cells are best defined functionally, as a subpopulation of tumor cells that can enrich for tumorigenic property and can regenerate heterogeneity of the original tumor. Circulating tumor cells are cells that have detached from a primary tumor and circulate in the bloodstream. They may constitute seeds for subsequent growth of additional tumors (metastasis) in different tissues. Advances in molecular imaging have allowed a deeper understanding of the in vivo behavior of stem cells and have proven to be indispensable in preclinical and clinical studies. One of the first imaging modalities for monitoring pluripotent stem cells in vivo, magnetic resonance imaging (MRI) offers high spatial and temporal resolution to obtain detailed morphological and functional information. Advantages of radioscintigraphic techniques include their picomolar sensitivity, good tissue penetration, and translation to clinical applications. Radionuclide imaging is the sole direct labeling technique used thus far in human studies, involving both autologous bone marrow derived and peripheral stem cells. PMID:22848220

Analyzing psychotherapy process as intersubjective sensemaking: an approach based on discourse analysis and neural networks.

PubMed

Nitti, Mariangela; Ciavolino, Enrico; Salvatore, Sergio; Gennaro, Alessandro

2010-09-01

The authors propose a method for analyzing the psychotherapy process: discourse flow analysis (DFA). DFA is a technique representing the verbal interaction between therapist and patient as a discourse network, aimed at measuring the therapist-patient discourse ability to generate new meanings through time. DFA assumes that the main function of psychotherapy is to produce semiotic novelty. DFA is applied to the verbatim transcript of the psychotherapy. It defines the main meanings active within the therapeutic discourse by means of the combined use of text analysis and statistical techniques. Subsequently, it represents the dynamic interconnections among these meanings in terms of a "discursive network." The dynamic and structural indexes of the discursive network have been shown to provide a valid representation of the patient-therapist communicative flow as well as an estimation of its clinical quality. Finally, a neural network is designed specifically to identify patterns of functioning of the discursive network and to verify the clinical validity of these patterns in terms of their association with specific phases of the psychotherapy process. An application of the DFA to a case of psychotherapy is provided to illustrate the method and the kinds of results it produces.

75 FR 22434 - Exelon Nuclear Texas Holdings, LLC; Notice of Receipt and Availability of Application for an...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... for a construction permit (CP) or combined license (COL) for a nuclear power facility. The ESP process...), the permit holder may reference the permit in an application for a CP or COL. Subsequent Federal...

Clinical Implications of a Dimensional Approach: The Normal:Abnormal Spectrum of Early Irritability.

PubMed

Wakschlag, Lauren S; Estabrook, Ryne; Petitclerc, Amelie; Henry, David; Burns, James L; Perlman, Susan B; Voss, Joel L; Pine, Daniel S; Leibenluft, Ellen; Briggs-Gowan, Margaret L

2015-08-01

The importance of dimensional approaches is widely recognized, but an empirical base for clinical application is lacking. This is particularly true for irritability, a dimensional phenotype that cuts across many areas of psychopathology and manifests early in life. We examine longitudinal, dimensional patterns of irritability and their clinical import in early childhood. Irritability was assessed longitudinally over an average of 16 months in a clinically enriched, diverse community sample of preschoolers (N = 497; mean = 4.2 years; SD = 0.8). Using the Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) as a developmentally sensitive indicator of early childhood irritability, we examined its convergent/divergent, clinical, and incremental predictive validity, and modeled its linear and nonlinear associations with clinical risk. The Temper Loss scale demonstrated convergent and divergent validity to child and maternal factors. In multivariate analyses, Temper Loss predicted mood (separation anxiety disorder [SAD], generalized anxiety disorder [GAD], and depression/dysthymia), disruptive (oppositional defiant disorder [ODD], attention-deficit/hyperactivity disorder [ADHD], and conduct disorder [CD]) symptoms. Preschoolers with even mildly elevated Temper Loss scale scores showed substantially increased risk of symptoms and disorders. For ODD, GAD, SAD, and depression, increases in Temper Loss scale scores at the higher end of the dimension had a greater impact on symptoms relative to increases at the lower end. Temper Loss scale scores also showed incremental validity over DSM-IV disorders in predicting subsequent impairment. Finally, accounting for the substantial heterogeneity in longitudinal patterns of Temper Loss significantly improved prediction of mood and disruptive symptoms. Dimensional, longitudinal characterization of irritability informs clinical prediction. A vital next step will be empirically generating parameters for the incorporation of dimensional information into clinical decision-making with reasonable certainty. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.

The Photodynamic Bone Stabilization System: a minimally invasive, percutaneous intramedullary polymeric osteosynthesis for simple and complex long bone fractures.

PubMed

Vegt, Paul; Muir, Jeffrey M; Block, Jon E

2014-01-01

The treatment of osteoporotic long bone fractures is difficult due to diminished bone density and compromised biomechanical integrity. The majority of osteoporotic long bone fractures occur in the metaphyseal region, which poses additional problems for surgical repair due to increased intramedullary volume. Treatment with internal fixation using intramedullary nails or plating is associated with poor clinical outcomes in this patient population. Subsequent fractures and complications such as screw pull-out necessitate additional interventions, prolonging recovery and increasing health care costs. The Photodynamic Bone Stabilization System (PBSS) is a minimally invasive surgical technique that allows clinicians to repair bone fractures using a light-curable polymer contained within an inflatable balloon catheter, offering a new treatment option for osteoporotic long bone fractures. The unique polymer compound and catheter application provides a customizable solution for long bone fractures that produces internal stability while maintaining bone length, rotational alignment, and postsurgical mobility. The PBSS has been utilized in a case series of 41 fractures in 33 patients suffering osteoporotic long bone fractures. The initial results indicate that the use of the light-cured polymeric rod for this patient population provides excellent fixation and stability in compromised bone, with a superior complication profile. This paper describes the clinical uses, procedural details, indications for use, and the initial clinical findings of the PBSS.

Mechanisms and therapeutic effectiveness of lactobacilli

PubMed Central

Di Cerbo, Alessandro; Palmieri, Beniamino; Aponte, Maria; Morales-Medina, Julio Cesar; Iannitti, Tommaso

2016-01-01

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects. PMID:26578541

Longitudinal noninvasive magnetic resonance imaging of brain microhemorrhages in BACE inhibitor-treated APP transgenic mice.

PubMed

Beckmann, Nicolau; Doelemeyer, Arno; Zurbruegg, Stefan; Bigot, Karine; Theil, Diethilde; Frieauff, Wilfried; Kolly, Carine; Moulin, Pierre; Neddermann, Daniel; Kreutzer, Robert; Perrot, Ludovic; Brzak, Irena; Jacobson, Laura H; Staufenbiel, Matthias; Neumann, Ulf; Shimshek, Derya R

2016-09-01

Currently, several immunotherapies and BACE (Beta Site APP Cleaving Enzyme) inhibitor approaches are being tested in the clinic for the treatment of Alzheimer's disease. A crucial mechanism-related safety concern is the exacerbation of microhemorrhages, which are already present in the majority of Alzheimer patients. To investigate potential safety liabilities of long-term BACE inhibitor therapy, we used aged amyloid precursor protein (APP) transgenic mice (APP23), which robustly develop cerebral amyloid angiopathy. T2*-weighted magnetic resonance imaging (MRI), a translational method applicable in preclinical and clinical studies, was used for the detection of microhemorrhages throughout the entire brain, with subsequent histological validation. Three-dimensional reconstruction based on in vivo MRI and serial Perls' stained sections demonstrated a one-to-one matching of the lesions thus allowing for their histopathological characterization. MRI detected small Perls' positive areas with a high spatial resolution. Our data demonstrate that volumetric assessment by noninvasive MRI is well suited to monitor cerebral microhemorrhages in vivo. Furthermore, 3 months treatment of aged APP23 with the potent BACE-inhibitor NB-360 did not exacerbate microhemorrhages in contrast to Aβ-antibody β1. These results substantiate the safe use of BACE inhibitors regarding microhemorrhages in long-term clinical studies for the treatment of Alzheimer's disease. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The Photodynamic Bone Stabilization System: a minimally invasive, percutaneous intramedullary polymeric osteosynthesis for simple and complex long bone fractures

PubMed Central

Vegt, Paul; Muir, Jeffrey M; Block, Jon E

2014-01-01

The treatment of osteoporotic long bone fractures is difficult due to diminished bone density and compromised biomechanical integrity. The majority of osteoporotic long bone fractures occur in the metaphyseal region, which poses additional problems for surgical repair due to increased intramedullary volume. Treatment with internal fixation using intramedullary nails or plating is associated with poor clinical outcomes in this patient population. Subsequent fractures and complications such as screw pull-out necessitate additional interventions, prolonging recovery and increasing health care costs. The Photodynamic Bone Stabilization System (PBSS) is a minimally invasive surgical technique that allows clinicians to repair bone fractures using a light-curable polymer contained within an inflatable balloon catheter, offering a new treatment option for osteoporotic long bone fractures. The unique polymer compound and catheter application provides a customizable solution for long bone fractures that produces internal stability while maintaining bone length, rotational alignment, and postsurgical mobility. The PBSS has been utilized in a case series of 41 fractures in 33 patients suffering osteoporotic long bone fractures. The initial results indicate that the use of the light-cured polymeric rod for this patient population provides excellent fixation and stability in compromised bone, with a superior complication profile. This paper describes the clinical uses, procedural details, indications for use, and the initial clinical findings of the PBSS. PMID:25540600

The frequency of clinical pregnancy and implantation rate after cultivation of embryos in a medium with granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with preceding failed attempts of ART.

PubMed

Tevkin, S; Lokshin, V; Shishimorova, M; Polumiskov, V

2014-10-01

The application in IVF practice of modern techniques can improve positive outcome of each cycle in the assisted reproductive technology (ART) programs and the effectiveness of treatment as a whole. There are embryos in the female reproductive tract in physiological medium which contain various cytokines and growth factors. It plays an important role in the regulation of normal embryonic development, improve implantation and subsequently optimizing the development of the fetus and the placenta. Granulocyte macrophage colony-stimulating factor (GM-CSF is one of the cytokines playing an important role in reproductive function. Addition of recombinant GM-CSF to the culture medium can makes closer human embryos culture to in vivo conditions and improve the efficacy ART cycles. The analysis of culture embryos in EmbryoGen medium has shown that fertilization rate embryo culture and transfer to patients with previous unsuccessful attempts increases clinical pregnancy rate compared to the control group 39.1 versus 27.8%, respectively. It is noted that the implantation rate (on 7 weeks' gestation) and progressive clinical pregnancy rate (on 12 weeks' gestation) were significantly higher in group embryos culture in EmbryoGen medium compared to standard combination of medium (ISM1+VA), and were 20.4 and 17.4% versus 11.6 and 9.1%, respectively.

Tooth wear prevention: a quantitative and qualitative in vitro study.

PubMed

Kaidonis, J A; Gratiaen, J; Bhatia, N; Richards, L C; Townsend, G C

2003-03-01

Management of tooth wear from grinding presents a significant clinical challenge. Acrylic nightguards are often used to protect the teeth, but many patients still grind with these appliances. This study aimed to test the effectiveness of three lubricants in reducing enamel wear by using an electro-mechanical machine under controlled conditions, with a view to undertaking a subsequent longitudinal clinical study. Sectioned tooth specimens were worn against each other under different loads and with the addition of three different lubricants: calcium fluoride (CaF) powder, olive-oil, and a combination of calcium fluoride with olive-oil in the form of a slurry. Wear rates of enamel only were quantified by weighing the specimens, and resin replicas of the worn tooth surfaces were made for examination under a scanning electron microscope. All three lubricants reduced the amount of enamel wear significantly compared with wearing specimens without adding lubricants. Wear rate was influenced by the type of lubricant and the load applied. Wear rates were significantly less for olive-oil and the olive-oil/CaF slurry compared with CaF alone. The microwear detail differed between the three lubricants. This study has shown that enamel wear can be reduced using dry or wet lubricants between opposing teeth that are worn under controlled conditions. Further research is required to clarify their possible clinical applications.

Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations.

PubMed

Oddo, Mauro; Poole, Daniele; Helbok, Raimund; Meyfroidt, Geert; Stocchetti, Nino; Bouzat, Pierre; Cecconi, Maurizio; Geeraerts, Thomas; Martin-Loeches, Ignacio; Quintard, Hervé; Taccone, Fabio Silvio; Geocadin, Romergryko G; Hemphill, Claude; Ichai, Carole; Menon, David; Payen, Jean-François; Perner, Anders; Smith, Martin; Suarez, José; Videtta, Walter; Zanier, Elisa R; Citerio, Giuseppe

2018-04-01

To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions-using a sequential approach to avoid biases and misinterpretations-was used to generate the final consensus statement. The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

[Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations].

PubMed

Aach, M; Meindl, R C; Geßmann, J; Schildhauer, T A; Citak, M; Cruciger, O

2015-02-01

Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Clinical Computer Applications in Mental Health

PubMed Central

Greist, John H.; Klein, Marjorie H.; Erdman, Harold P.; Jefferson, James W.

1982-01-01

Direct patient-computer interviews were among the earliest applications of computing in medicine. Yet patient interviewing and other clinical applications have lagged behind fiscal/administrative uses. Several reasons for delays in the development and implementation of clinical computing programs and their resolution are discussed. Patient interviewing, clinician consultation and other applications of clinical computing in mental health are reviewed.

Developing Abilities to Navigate Through the Grey Zones in Complex Environments: Nurses' Reasons for Applying to a Clinical Ethics Residency for Nurses.

PubMed

Jurchak, Martha; Grace, Pamela J; Lee, Susan M; Willis, Danny G; Zollfrank, Angelika A; Robinson, Ellen M

2017-07-01

Nurses face complex ethical issues in practice and have to determine appropriate actions. An inability to conceptualize or follow a preferred course of action can give rise to moral uncertainty or moral distress. Both moral uncertainty and moral distress are problematic for nurses and their patients. A program designed to increase nurse confidence in moral decision making, the clinical ethics residency for nurses (CERN), was offered selectively to nurses affiliated with two academic medical centers. This is a report of the analysis of their application essays. Over a 3-year period, 67 application essays were analyzed using conventional content analysis. Applicants comprised one third advanced practice nurses (APNs) and two thirds staff nurses. They were asked to describe their reasons for interest in the CERN and how they would apply the knowledge gained. For conventional content analyses, no theoretical presumptions are used; rather, codes are identified from the data in an iterative manner and eventually collapsed into themes. Initially, broad themes were identified by the CERN team. Subsequently, in-depth and recursive readings were completed by a subset of three members, resulting in refinement of themes and subthemes. The overarching theme identified was "developing abilities to navigate through the 'grey zones' in complex environments." Three subthemes were: (a) nurses encountering patients who are chronically critically ill, culturally diverse, and presenting with complex circumstances; (b) nurses desiring enhanced ethics knowledge and skills to improve quality of care, understand different perspectives, and act as a resource for others; and (c) nurses supporting and facilitating patient-centered ethical decision making. Findings are consistent with those appearing in the international literature but provide a more cohesive and comprehensive account than previously, and hold promise for the development of educational and policy strategies to address moral distress and uncertainty. This study is relevant to clinical practice in its verification of the need nurses have for ethics knowledge, skill refinement, and application through communication. These findings affirmed the challenge that nurses feel in communicating their ethical concerns in an effective and engaging way and their commitment to advocacy and improvement in the quality of care for patients. © 2017 Sigma Theta Tau International.

Relationship of clinical and quality of life trajectories following the onset of seizures: findings from the UK MESS Study.

PubMed

Jacoby, Ann; Lane, Steven; Marson, Anthony; Baker, Gus A

2011-05-01

We defined a series of clinical trajectories represented among adult patients with new-onset seizures across a 4-year follow-up period; and linked these clinical trajectories to the quality of life (QOL) profiles and trajectories of those experiencing them. We examined both between- and within-group differences. Analyses were based on 253 individuals completing QOL questionnaires at baseline and 2 and 4 years subsequently. Based on patient self-report, we defined five "clinical trajectory" groups: individuals experiencing a single seizure only; individuals entering early remission; individuals experiencing late remission; individuals initially becoming seizure-free but subsequently relapsing; individuals with seizures persisting throughout follow-up. QOL profiles at each time point were compared using a validated QOL battery, NEWQOL. Even at baseline, there were significant between-group differences, with patients experiencing a single seizure only reporting the best QOL profile and those with seizures subsequently persisting across all time points reporting the worst. By 2 years, the QOL profiles of individuals experiencing early remission were similar to those of single seizure patients, as were those for late remission and relapse patients. A consistent pattern was seen, with "single seizure" individuals doing best and individuals with persistent seizures doing worst. Of particular concern is that even at baseline, individuals whose seizures persisted were doing poorly for QOL, suggesting the possibility that underlying neurobiologic mechanisms were operating. In contrast, our findings support previous reports of only short-lived and small QOL decrements for individuals experiencing a single or few seizures. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Four-year follow-up of transient ischemic attacks, strokes, and mimics: a retrospective transient ischemic attack clinic cohort study.

PubMed

Dutta, Dipankar; Bowen, Emily; Foy, Chris

2015-05-01

There is limited information on outcomes from rapid access transient ischemic attack (TIA) clinics. We present 4-year outcomes of TIAs, strokes, and mimics from a UK TIA clinic database. All patients referred between April 2010 and May 2012 were retrospectively identified and outcomes determined. End points were stroke, myocardial infarction, any vascular event (TIA, stroke, or myocardial infarction), and all-cause death. Data were analyzed by survival analysis. Of 1067 patients, 31.6% were TIAs, 18% strokes, and 50.4% mimics. Median assessment time was 4.5 days from onset and follow-up was for 34.9 months. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke, and 2.0% of mimics at the end of follow-up. Stroke risk at 90 days was 1.3% for patients diagnosed as TIA or stroke. Compared with mimics, hazard ratios for subsequent stroke were 3.88 (1.90-7.91) for TIA and 5.84 (2.81-12.11) for stroke. Hazard ratio for any subsequent vascular event was 2.91 (1.97-4.30) for TIA and 2.83 (1.81-4.41) for stroke. Hazard ratio for death was 1.68 (1.10-2.56) for TIA and 2.19 (1.38-3.46) for stroke. Our results show a lower 90-day stroke incidence after TIA or minor stroke than in earlier studies, suggesting that rapid access daily TIA clinics may be having a significant effect on reducing strokes. © 2015 American Heart Association, Inc.

[Instituto de Investigaciones Clinicas "Dr. Américo Negrette": 55 years of excellent research versus global economic recession].

PubMed

Valero Cedeño, Nereida Josefina

2014-12-01

The Instituto de Investigaciones Clínicas "Dr. Américo Negrette" belongs to the Faculty of Medicine at University of Zulia in Maracaibo, Zulia State, Venezuela. It was created on December 4, 1959 by Dr. Américo Negrette. Today, with 55 years of existence, the Institute seeks to fulfill the mission that characterizes it, based on the values instilled by its founder and maintained by subsequent generations, whose research projects are implemented through seven research sections: Biochemistry, Hematologic Research, Neuropharmacology and Neuroscience, Immunology and Cell Biology, Clinical Neurochemistry, Parasitology and Virology. The research originated in these laboratories have become national and international points of reference, despite the current economic situation with budget deficits that put at risk the quality and originality of their projects with negative consequences on the productivity and applications for health population, reasons of biomedical research.

Recent technological advances in pediatric brain tumor surgery.

PubMed

Zebian, Bassel; Vergani, Francesco; Lavrador, José Pedro; Mukherjee, Soumya; Kitchen, William John; Stagno, Vita; Chamilos, Christos; Pettorini, Benedetta; Mallucci, Conor

2017-01-01

X-rays and ventriculograms were the first imaging modalities used to localize intracranial lesions including brain tumors as far back as the 1880s. Subsequent advances in preoperative radiological localization included computed tomography (CT; 1971) and MRI (1977). Since then, other imaging modalities have been developed for clinical application although none as pivotal as CT and MRI. Intraoperative technological advances include the microscope, which has allowed precise surgery under magnification and improved lighting, and the endoscope, which has improved the treatment of hydrocephalus and allowed biopsy and complete resection of intraventricular, pituitary and pineal region tumors through a minimally invasive approach. Neuronavigation, intraoperative MRI, CT and ultrasound have increased the ability of the neurosurgeon to perform safe and maximal tumor resection. This may be facilitated by the use of fluorescing agents, which help define the tumor margin, and intraoperative neurophysiological monitoring, which helps identify and protect eloquent brain.

[Application of an OPT model in a paediatric nursing clinical case in primary health care].

PubMed

Rifà Ros, Rosa; Pérez Pérez, Isabel

2011-01-01

This article describes the assessment and nursing diagnostic hypothesis generation on a 10 years old child with a parietal contusion who attended the health care centre with his mother. The health centre is located in a rural area in Catalonia, and a paediatric nurse was placed in charge of the child. In the assessment and the subsequent information analysis, the nurse identified an unhealthy situation for the correct development of the child. The situation required the mother's intervention and a change in her habits and behaviours. For the approach of the case study, the OPT model (Outcome Present-state Testing) by Pesut and Herdman was used. The assessment was made by using Marjory Gordon's Functional Health Patterns assessment, and the NANDA-I nursing diagnoses taxonomy, NOC Outcomes taxonomy and NIC Interventions taxonomy was used for the diagnoses and planning. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Age-related reduction of cerebral ischemic preconditioning: myth or reality?

PubMed Central

Della-Morte, David; Cacciatore, Francesco; Salsano, Elisa; Pirozzi, Gilda; Genio, Maria Teresa Del; D’Antonio, Iole; Gargiulo, Gaetano; Palmirotta, Raffaele; Guadagni, Fiorella; Rundek, Tatjana; Abete, Pasquale

2013-01-01

Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed. PMID:24204128

78 FR 22269 - International Conference on Harmonisation; Draft Guidance on M7 Assessment and Control of DNA...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.'' The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The draft guidance emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that reside or are reasonably expected to reside in a final drug substance or product, taking into consideration the intended conditions of human use. The draft guidance is intended to provide guidance for new drug substances and new drug products during their clinical development and subsequent applications for marketing.

Droplet Microfluidics for Chip-Based Diagnostics

PubMed Central

Kaler, Karan V. I. S.; Prakash, Ravi

2014-01-01

Droplet microfluidics (DMF) is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays. PMID:25490590

3D printing of a wearable personalized oral delivery device: A first-in-human study

PubMed Central

Brambilla, Davide

2018-01-01

Despite the burgeoning interest in three-dimensional (3D) printing for the manufacture of customizable oral dosage formulations, a U.S. Food and Drug Administration–approved tablet notwithstanding, the full potential of 3D printing in pharmaceutical sciences has not been realized. In particular, 3D-printed drug-eluting devices offer the possibility for personalization in terms of shape, size, and architecture, but their clinical applications have remained relatively unexplored. We used 3D printing to manufacture a tailored oral drug delivery device with customizable design and tunable release rates in the form of a mouthguard and, subsequently, evaluated the performance of this system in the native setting in a first-in-human study. Our proof-of-concept work demonstrates the immense potential of 3D printing as a platform for the development and translation of next-generation drug delivery devices for personalized therapy. PMID:29750201

Transformable liquid-metal nanomedicine

PubMed Central

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-01-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity. PMID:26625944

Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in Monoclonal Antibodies.

PubMed

Agrawal, Neeraj J; Dykstra, Andrew; Yang, Jane; Yue, Hai; Nguyen, Xichdao; Kolvenbach, Carl; Angell, Nicolas

2018-05-01

Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information. Since antibody sequence information is available in the discovery phase, the in silico method can be applied very early on to identify the oxidation-labile methionine residues and subsequently address the oxidation liability. We believe that the in silico method for methionine oxidation liability assessment can aid in antibody discovery and development phase to address the liability in a more rational way. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Curing genetic disease with gene therapy.

PubMed

Williams, David A

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile.

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

PubMed Central

2015-01-01

Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core–shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

The European hospital exemption clause-new option for gene therapy?

PubMed

Buchholz, Christian J; Sanzenbacher, Ralf; Schüle, Silke

2012-01-01

Gene-therapy medicinal products are currently applied to patients enrolled in authorized clinical trials to demonstrate safety and efficacy. Given a positive outcome, marketing authorization can subsequently be achieved via the centralized procedure coordinated by the European Medicines Agency. With Regulation (EC) No. 1394/2007 in force, advanced therapy medicinal products, including gene- and cell-therapy products, can be excepted from the obligation of obtaining a marketing authorization via the centralized procedure under specific conditions (so-called "hospital exemption"). This hospital exemption allows the application of gene-therapy medicinal products prepared on a non-routine basis for an individual patient and used under the exclusive professional responsibility of a medical practitioner. Here, we explain the requirements to be fulfilled in order to fall under this exemption, the implementation of this regulation into the German national legislation, and its impact on gene-therapy product development in the future.

Optical trapping for complex fluid microfluidics

NASA Astrophysics Data System (ADS)

Vestad, Tor; Oakey, John; Marr, David W. M.

2004-10-01

Many proposed applications of microfluidics involve the manipulation of complex fluid mixtures such as blood or bacterial suspensions. To sort and handle the constituent particles within these suspensions, we have developed a miniaturized automated cell sorter using optical traps. This microfluidic cell sorter offers the potential to perform chip-top microbiology more rapidly and with less associated hardware and preparation time than other techniques currently available. To realize the potential of this technology in practical clinical and consumer lab-on-a-chip devices however, microscale control of not only particulates but also the fluid phase must be achieved. To address this, we have developed a mechanical fluid control scheme that integrates well with our optical separations approach. We demonstrate here a combined technique, one that employs both mechanical actuation and optical trapping for the precise control of complex suspensions. This approach enables both cell and particle separations as well as the subsequent fluid control required for the completion of complex analyses.

A stimulus control technique for improving the efficacy of an established toilet training program.

PubMed

Taylor, S; Cipani, E; Clardy, A

1994-06-01

Standard toilet training regimens used with children with developmental disabilities have demonstrated effectiveness at achieving bladder and bowel continence. However, in some clinical applications in everyday practice, success has not been achieved, necessitating research into possible modifications of the current approaches. A widely used toilet training program was modified to reduce toileting accidents of a referred child. The modification involved the assessment of the discriminative stimulus for eliminating, namely, his undergarments. By removing the undergarments when an elimination became imminent, an "errorless" learning paradigm was established that allowed for more rapid and enduring acquisition of toileting skills than seen in previous training attempts. The results indicate the present procedure could expedite training for individuals who are difficult to teach appropriate toileting skills through an analysis of the controlling antecedent stimulus for accidents and subsequent manipulation of such stimuli.

Expression microdissection adapted to commercial laser dissection instruments

PubMed Central

Hanson, Jeffrey C; Tangrea, Michael A; Kim, Skye; Armani, Michael D; Pohida, Thomas J; Bonner, Robert F; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R

2016-01-01

Laser-based microdissection facilitates the isolation of specific cell populations from clinical or animal model tissue specimens for molecular analysis. Expression microdissection (xMD) is a second-generation technology that offers considerable advantages in dissection capabilities; however, until recently the method has not been accessible to investigators. This protocol describes the adaptation of xMD to commonly used laser microdissection instruments and to a commercially available handheld laser device in order to make the technique widely available to the biomedical research community. The method improves dissection speed for many applications by using a targeting probe for cell procurement in place of an operator-based, cell-by-cell selection process. Moreover, xMD can provide improved dissection precision because of the unique characteristics of film activation. The time to complete the protocol is highly dependent on the target cell population and the number of cells needed for subsequent molecular analysis. PMID:21412274

Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives

PubMed Central

Üner, Melike; Yener, Gülgün

2007-01-01

Solid lipid nanoparticles (SLN) have been reported to be an alternative system to emulsions, liposomes, microparticles and their polymeric counterparts for various application routes since the early 1990s due to their advantages. Various research groups have also increasingly focused on improving their stability in body fluids after administration by coating of particles with hydrophilic molecules such as poly(ethylene)glycol (PEG) derivatives. Altering surface characteristics by coating SLN with hydrophilic molecules improves plasma stability and biodistribution, and subsequent bioavailability of drugs entrapped. Their storage stability is also increased. This paper basicly reviews types of SLN, principles of drug loading and models of drug incorporation. The influence of PEG coating on particle size and surface characteristics is discussed followed by alteration in pharmacokinetics and bioavailability of drugs in order to target the site of action via SLN. The future direction of research and clinical implications of SLN is also considered. PMID:18019829

Curing Genetic Disease with Gene Therapy

PubMed Central

Williams, David A.

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile. PMID:25125725

Personalized Preventive Medicine: Genetics and the Response to Regular Exercise in Preventive Interventions

PubMed Central

Bouchard, Claude; Antunes-Correa, Ligia M.; Ashley, Euan A.; Franklin, Nina; Hwang, Paul M.; Mattsson, C. Mikael; Negrao, Carlos E.; Phillips, Shane A.; Sarzynski, Mark A.; Wang, Ping-yuan; Wheeler, Matthew T.

2014-01-01

Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications. PMID:25559061

Transformable liquid-metal nanomedicine

NASA Astrophysics Data System (ADS)

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-12-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Incidence of tympanic membrane perforation after intratympanic steroid treatment through myringotomy tubes.

PubMed

Rutt, Amy L; Hawkshaw, Mary J; Sataloff, Robert T

2011-04-01

Intratympanic (IT) steroids are often used to treat inner ear disorders such as sudden idiopathic sensorineural hearing loss, autoimmune inner ear disease, and Ménière disease. Administration of corticosteroids via IT injection, via application with a pledget to the round window, or via catheter has been used for this purpose. The frequency of adverse events related to the IT injection of steroids is low, with pain, short-lasting vertigo, otitis media, and tympanic perforations being the most common complications. However, the safety of IT steroid therapy has not yet been established in a randomized clinical trial. In this article, we discuss a group of 11 patients with sensorineural hearing loss who underwent myringotomy and tube placement for home-based dexamethasone instillation and subsequently developed the complication of tympanic membrane perforation. It appears that there is a significantly increased incidence of tympanic membrane perforations in this population.

Albumin as a "Trojan Horse" for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting.

PubMed

Yin, Qian; Tang, Li; Cai, Kaimin; Yang, Xujuan; Yin, Lichen; Zhang, Yanfeng; Dobrucki, Lawrence W; Helferich, William G; Fan, Timothy M; Cheng, Jianjun

2018-05-01

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.

Text de-identification for privacy protection: a study of its impact on clinical text information content.

PubMed

Meystre, Stéphane M; Ferrández, Óscar; Friedlin, F Jeffrey; South, Brett R; Shen, Shuying; Samore, Matthew H

2014-08-01

As more and more electronic clinical information is becoming easier to access for secondary uses such as clinical research, approaches that enable faster and more collaborative research while protecting patient privacy and confidentiality are becoming more important. Clinical text de-identification offers such advantages but is typically a tedious manual process. Automated Natural Language Processing (NLP) methods can alleviate this process, but their impact on subsequent uses of the automatically de-identified clinical narratives has only barely been investigated. In the context of a larger project to develop and investigate automated text de-identification for Veterans Health Administration (VHA) clinical notes, we studied the impact of automated text de-identification on clinical information in a stepwise manner. Our approach started with a high-level assessment of clinical notes informativeness and formatting, and ended with a detailed study of the overlap of select clinical information types and Protected Health Information (PHI). To investigate the informativeness (i.e., document type information, select clinical data types, and interpretation or conclusion) of VHA clinical notes, we used five different existing text de-identification systems. The informativeness was only minimally altered by these systems while formatting was only modified by one system. To examine the impact of de-identification on clinical information extraction, we compared counts of SNOMED-CT concepts found by an open source information extraction application in the original (i.e., not de-identified) version of a corpus of VHA clinical notes, and in the same corpus after de-identification. Only about 1.2-3% less SNOMED-CT concepts were found in de-identified versions of our corpus, and many of these concepts were PHI that was erroneously identified as clinical information. To study this impact in more details and assess how generalizable our findings were, we examined the overlap between select clinical information annotated in the 2010 i2b2 NLP challenge corpus and automatic PHI annotations from our best-of-breed VHA clinical text de-identification system (nicknamed 'BoB'). Overall, only 0.81% of the clinical information exactly overlapped with PHI, and 1.78% partly overlapped. We conclude that automated text de-identification's impact on clinical information is small, but not negligible, and that improved clinical acronyms and eponyms disambiguation could significantly reduce this impact. Copyright © 2014 Elsevier Inc. All rights reserved.

Application of biocatalysts to Space Station ECLSS and PMMS water reclamation

NASA Technical Reports Server (NTRS)

Jolly, Clifford D.; Bagdigian, Robert M.

1989-01-01

Immobilized enzyme reactors have been developed and tested for potential water reclamation applications in the Space Station Freedom Environmental Control and Life Support System (ECLSS) and Process Materials Management System (PMMS). The reactors convert low molecular weight organic contaminants found in ECLSS and PMMS wastewaters to compounds that are more efficiently removed by existing technologies. Demonstration of the technology was successfully achieved with two model reactors. A packed bed reactor containing immobilized urease was found to catalyze the complete decomposition of urea to by-products that were subsequently removed using conventional ion exchange results. A second reactor containing immobilized alcohol oxidase showed promising results relative to its ability to convert methanol and ethanol to the corresponding aldehydes for subsequent removal. Preliminary assessments of the application of biocatalysts to ECLSS and PMMS water reclamation sytems are presented.

Work Ability Index predicts application for disability pension after work-related medical rehabilitation for chronic back pain.

PubMed

Bethge, Matthias; Gutenbrunner, Christoph; Neuderth, Silke

2013-11-01

To determine whether the Work Ability Index (WAI), a short 7-item self-report questionnaire addressing issues of perceived disability, impairment, and expectations for resuming work, predicts application for disability pension, recommendations for further treatment, and other adverse work-related criteria in patients with chronic back pain after rehabilitation. Cohort study with 3-month follow-up. Seven inpatient rehabilitation centers. Patients (N=294; 168 women; mean age, 49.9y) with chronic back pain. The WAI was completed at the beginning of rehabilitation. All patients were treated according to the German rehabilitation guidelines for chronic back pain and work-related medical rehabilitation. Application for disability pension, as assessed by a postal questionnaire 3 months after discharge. Receiver operating characteristic curve analysis of the association between the WAI at baseline and subsequent application for disability pension revealed an area under the curve of .80 (95% confidence interval [CI], .62-.97). Youden index was highest when the WAI cutoff value was ≤20 points (sensitivity, 72.7%; specificity, 82.2%; total correct classification, 81.7%). After adjusting for age and sex, persons with a baseline WAI score of ≤20 points had 15.6 times (95% CI, 3.6-68.2) higher odds of subsequent application for disability pension, 4.9 times (95% CI, 1.5-16.8) higher odds of unemployment, and 6 times (95% CI, 2.4-15.2) higher odds of long-term sick leave at follow-up. The WAI could help rehabilitation professionals identify patients with back pain with a high risk of a subsequent application for disability pension. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cryopreservation: Vitrification and Controlled Rate Cooling.

PubMed

Hunt, Charles J

2017-01-01

Cryopreservation is the application of low temperatures to preserve the structural and functional integrity of cells and tissues. Conventional cooling protocols allow ice to form and solute concentrations to rise during the cryopreservation process. The damage caused by the rise in solute concentration can be mitigated by the use of compounds known as cryoprotectants. Such compounds protect cells from the consequences of slow cooling injury, allowing them to be cooled at cooling rates which avoid the lethal effects of intracellular ice. An alternative to conventional cooling is vitrification. Vitrification methods incorporate cryoprotectants at sufficiently high concentrations to prevent ice crystallization so that the system forms an amorphous glass thus avoiding the damaging effects caused by conventional slow cooling. However, vitrification too can impose damaging consequences on cells as the cryoprotectant concentrations required to vitrify cells at lower cooling rates are potentially, and often, harmful. While these concentrations can be lowered to nontoxic levels, if the cells are ultra-rapidly cooled, the resulting metastable system can lead to damage through devitrification and growth of ice during subsequent storage and rewarming if not appropriately handled.The commercial and clinical application of stem cells requires robust and reproducible cryopreservation protocols and appropriate long-term, low-temperature storage conditions to provide reliable master and working cell banks. Though current Good Manufacturing Practice (cGMP) compliant methods for the derivation and banking of clinical grade pluripotent stem cells exist and stem cell lines suitable for clinical applications are available, current cryopreservation protocols, whether for vitrification or conventional slow freezing, remain suboptimal. Apart from the resultant loss of valuable product that suboptimal cryopreservation engenders, there is a danger that such processes will impose a selective pressure on the cells selecting out a nonrepresentative, freeze-resistant subpopulation. Optimizing this process requires knowledge of the fundamental processes that occur during the freezing of cellular systems, the mechanisms of damage and methods for avoiding them. This chapter draws together the knowledge of cryopreservation gained in other systems with the current state-of-the-art for embryonic and induced pluripotent stem cell preservation in an attempt to provide the background for future attempts to optimize cryopreservation protocols.

Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.

PubMed

Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry

2013-01-01

Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

Imaging in the assessment and management of athletic pubalgia.

PubMed

Robinson, Philip; Bhat, Vineet; English, Bryan

2011-02-01

This article reviews the clinical, anatomical, and biomechanical basis of pubalgia and relates it to the potential imaging findings and subsequent management. Although the magnetic resonance imaging features typically seen in symptomatic athletes are emphasized, this condition remains a complex clinical problem, and treatment addressing the functional rehabilitation of the entire region is highlighted. © Thieme Medical Publishers.

The Relationship between Method of Clinical Instruction in Radiography and Scores on the American Registry of Radiologic Technologists Certification Examination.

ERIC Educational Resources Information Center

Dowd, Steven B.

An examination was made of the relationship between clinical grade based on simulation and a subsequent outcome measurement, the national certification examination in radiography. Although the new "Essentials" developed by the Joint Review Committee in Education in Radiologic Technology discouraged use of simulation, the method had…

Management of dairy heifers and its relationships with the incidence of clinical mastitis.

PubMed

Parker, K I; Compton, C W R; Anniss, F M; Weir, A M; McDougal, S

2007-10-01

To describe aspects of management of dairy heifers before calving and determine risk factors for clinical mastitis postpartum in heifers, at the herd level, under pasture-based management systems in the Waikato and Taranaki regions of New Zealand. Dairy herdowners (n=578) provided information via a prospective survey about their practices for rearing heifers and management of mastitis. A proportion of herdowners (n=250) subsequently provided data on the cases of clinical mastitis in their herds, including the date, cow identification, age and quarter affected from cases occurring in the 4 months after the planned start of calving (PSC) in the subsequent lactation. The relationship between management factors and the proportion of heifers diagnosed with clinical mastitis within a herd was examined using bivariate and multivariate analyses. The herd average percentage of heifers with clinical mastitis was 13.6 (95% confidence interval (CI)=12.3-14.9)%, and multiparous cows with clinical mastitis was 9.0 (95% CI=8.2-9.8)% in the first 4 months of lactation. There were positive relationships between the proportion of heifers with clinical mastitis and average milk production per cow (kg milksolids/ lactation; p<0.001), number of cows milked per labour unit (p=0.003), stocking rate (<> 3.30 cows/ha; p=0.002), and incidence of clinical mastitis in multiparous cows (%/120 days; p<0.04), in the final multivariate model. The proportion of heifers with clinical mastitis per herd was lower in herds that milked their lactating cows in multiple groups (p=0.02). The risk of clinical mastitis in heifers was significantly associated with management practices. It may be possible to reduce the incidence of clinical mastitis in heifers by modification of management practices at the herd level, and further studies are required to investigate this.

Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding.

PubMed

Huang, Hsin-Chung; Yang, Hwai-I; Chang, Yu-Hsun; Chang, Rui-Jane; Chen, Mei-Huei; Chen, Chien-Yi; Chou, Hung-Chieh; Hsieh, Wu-Shiun; Tsao, Po-Nien

2012-12-01

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia. Copyright © 2012. Published by Elsevier B.V.

Lumbar Imaging with Reporting of Epidemiology (LIRE)- Protocol for a Pragmatic Cluster Randomized Trial

PubMed Central

Jarvik, Jeffrey G.; Comstock, Bryan A.; James, Kathryn T.; Avins, Andrew L.; Bresnahan, Brian W.; Deyo, Richard A.; Luetmer, Patrick H.; Friedly, Janna L.; Meier, Eric N.; Cherkin, Daniel C.; Gold, Laura S.; Rundell, Sean D.; Halabi, Safwan S.; Kallmes, David F.; Tan, Katherine W.; Turner, Judith A.; Kessler, Larry G.; Lavallee, Danielle C.; Stephens, Kari A.; Heagerty, Patrick J.

2015-01-01

Background Diagnostic imaging is often the first step in evaluating patients with back pain and likely functions as a “gateway” to a subsequent cascade of interventions. However, lumbar spine imaging frequently reveals incidental findings among normal, pain-free individuals suggesting that treatment of these “abnormalities” may not be warranted. Our prior work suggested that inserting the prevalence of imaging findings in patients without back pain into spine imaging reports may reduce subsequent interventions. We are now conducting a pragmatic cluster randomized clinical trial to test the hypothesis that inserting this prevalence data into lumbar spine imaging reports for studies ordered by primary care providers will reduce subsequent spine-related interventions. Methods/Design We are using a stepped wedge design that sequentially randomizes 100 primary care clinics at four health systems to receive either standard lumbar spine imaging reports, or reports containing prevalence data for common imaging findings in patients without back pain. We capture all outcomes passively through the electronic medical record. Our primary outcome is spine-related intervention intensity based on Relative Value Units (RVUs) during the following year. Secondary outcomes include subsequent prescriptions for opioid analgesics and cross-sectional lumbar spine re-imaging. Discussion If our study shows that adding prevalence data to spine imaging reports decreases subsequent back-related RVUs, this intervention could be easily generalized and applied to other kinds of testing, as well as other conditions where incidental findings may be common. Our study also serves as a model for cluster randomized trials that are minimal risk and highly pragmatic. PMID:26493088

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