Covert video monitoring in the assessment of medically unexplained symptoms in children.

PubMed

Wallace, Dustin P; Sim, Leslie A; Harrison, Tracy E; Bruce, Barbara K; Harbeck-Weber, Cynthia

2012-04-01

Diagnosis of medically unexplained symptoms (MUS) occurs after thorough evaluations have failed to identify a physiological cause for symptoms. However, families and providers may wonder if something has been missed, leading to reduced confidence in behavioral treatment. Confidence may be improved through the use of technology such as covert video monitoring to better assess functioning across settings. A 12-year-old male presented with progressive neurological decline, precipitated by chronic pain. After thorough evaluation and the failure of standard treatments (medical, rehabilitative, and psychological) covert video monitoring revealed that the patient demonstrated greater abilities when alone in his room. Negative reinforcement was used to initiate recovery, accompanied by positive reinforcement and a rehabilitative approach. Covert video monitoring assisted in three subsequent cases over the following 3 years. In certain complex cases, video monitoring can inform the assessment and treatment of MUS. Discussion includes ethical and practical considerations.

Vincristine-induced peripheral neuropathy in pediatric cancer patients

PubMed Central

Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L

2016-01-01

Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761

Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

PubMed

Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

2018-02-01

Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2-Surveillance for Treatment Complications and Disease Progression.

PubMed

McNamara, C; Sugrue, G; Murray, B; MacMahon, P J

2017-09-01

An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile. Special attention is given to the diagnosing of progressive multifocal leukoencephalopathy in patients treated with natalizumab as this is a key area in which neuroradiologists can contribute to improved patient outcomes. This article also outlines the aims of treatment and reviews the possibility of "no evidence of disease activity" becoming a treatment goal with the availability of more effective therapies. Potential future areas and technologies including image subtraction, brain volume measurement and advanced imaging techniques such as double inversion recovery are also reviewed. It is anticipated that such advancements in this rapidly developing field will improve the accuracy of monitoring an individual patient's response to treatment. © 2017 by American Journal of Neuroradiology.

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

[Prescribing monitoring in clinical practice: from enlightened empiricism to rational strategies].

PubMed

Buclin, Thierry; Herzig, Lilli

2013-05-15

Monitoring of a medical condition is the periodic measurement of one or several physiological or biological variables to detect a signal regarding its clinical progression or its response to treatment. We distinguish different medical situations between diagnostic, clinical and therapeutic process to apply monitoring. Many clinical, variables can be used for monitoring, once their intrinsic properties (normal range, critical difference, kinetics, reactivity) and external validity (pathophysiological importance, predictive power for clinical outcomes) are established. A formal conceptualization of monitoring is being developed and should support the rational development of monitoring strategies and their validation through appropriate clinical trials.

Current practices in laboratory monitoring of HIV infection

PubMed Central

Vajpayee, Madhu; Mohan, Teena

2011-01-01

After a diagnosis of HIV infection is made, the patient needs to be monitored using both clinical assessment and laboratory markers. HIV/AIDS monitoring is essential in guiding when to recommend initiation of therapy. Clinical monitoring will include staging of the HIV/AIDS disease using either the presence or absence of HIV-related signs and symptoms using the WHO staging system. Various laboratory methods can be used to monitor the disease progression and to guide whether the patient will need antiretroviral therapy or not. Laboratory monitoring for patients who are not on drugs is done to provide information about the stage of illness; to enable the clinician to make decisions on treatment and to give information on prognosis of the patient. Patients on drugs are monitored to assess their response to treatment with antiretroviral drugs and to detect any possible toxicity and improvement associated with the antiretroviral drugs. PMID:22310815

Improving drug addiction treatment in China.

PubMed

Tang, Yi-Lang; Hao, Wei

2007-07-01

To illustrate the current situation and problems of drug addiction in treatment China and propose suggestions. A descriptive study based on literature searched from Medline and the China National Knowledge Infrastructure database (1996-2007) and hand-picked references. Since the re-emergence of drug addiction in China in the early 1990s, there has been tremendous progress in drug addiction treatments in China, especially treatments for opiate addiction. However, many problems and challenges remain for improvement, including widespread negative attitudes towards drug abuse and drug-dependent individuals, the lack of evidence-based data on the efficacy of Chinese traditional medicine and the lack of a comprehensive and integrated system to organize all treatment resources and monitor treatment progress. The authors discuss the challenges that impede effective treatments of drug addiction and some suggestions are proposed. Implementing these suggestions can improve the outcome of treatment of drug-dependent individuals and benefit the whole society. China faces substantial drug addiction problems that appear to be worsening with time. Although much progress in drug addiction treatment has been made, improvement in many aspects is needed urgently.

The Role of Regular Home Practice in the Relaxation Treatment of Tension Headache.

ERIC Educational Resources Information Center

Blanchard, Edward B.; And Others

1991-01-01

Gave 27 tension headache sufferers progressive muscle relaxation (PMR) training, with 14 of those subjects also receiving home practice and application instructions. Compared to third group of sufferers (n=6) who merely monitored headache activity, both treated groups showed significant reduction in headache activity. Treatment groups did not…

Creating Abbreviated Rating Scales to Monitor Classroom Inattention-Overactivity, Aggression, and Peer Conflict: Reliability, Validity, and Treatment Sensitivity

ERIC Educational Resources Information Center

Volpe, Robert J.; Gadow, Kenneth D.

2010-01-01

Rating scales developed to measure child emotional and behavioral problems typically are so long as to make their use in progress monitoring impractical in typical school settings. This study examined two methods of selecting items from existing rating scales to create shorter instruments for use in assessing response to intervention. The…

Psychometric Evaluation of the Symptoms and Functioning Severity Scale (SFSS) Short Forms with Out-of-Home Care Youth

ERIC Educational Resources Information Center

Gross, Thomas J.; Duppong Hurley, Kristin; Lambert, Matthew C.; Epstein, Michael H.; Stevens, Amy L.

2015-01-01

Background: There is a need for brief progress monitoring measures of behavioral and emotional symptoms for youth in out-of-home care. The Symptoms and Functioning Severity Scale (SFSS; Bickman et al. in Manual of the peabody treatment progress battery. Vanderbilt University, Nashville, 2010) is one measure that has clinician and youth short forms…

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

PubMed

Tinmouth, Jill; Peeva, Valentina; Amare, Henok; Blitz, Sandra; Raboud, Janet; Sano, Marie; Steele, Leah; Salit, Irving E

2016-09-01

High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. This was a prospective cohort study. The study was conducted at an outpatient clinic at a tertiary care center in Toronto. Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. We measured the incidence of anal cancer per 100 person-years of follow-up. Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Diabetes Treatment Breakthrough.

ERIC Educational Resources Information Center

Baker, Shelly; And Others

1993-01-01

Eight experts in visual impairment respond briefly to reports that intensive monitoring of blood glucose levels by persons with diabetes can lead to a 70% reduction in the progression of detectable diabetic retinopathy. Comments are generally optimistic, though some cautions are raised. (DB)

The pros and cons of the QuantiFERON test for the diagnosis of tuberculosis, prediction of disease progression, and treatment monitoring.

PubMed

Ndzi, Elvis Ndukong; Nkenfou, Celine Nguefeu; Gwom, Luc Christian; Fainguem, Nadine; Fokam, Joseph; Pefura, Yone

2016-06-01

Tuberculosis (TB) is a re-emerging disease with the advent of human immunodeficiency virus/AIDS infections. Discovered in 1959, diagnosed by various approaches and treated with antibiotics, the treatment of TB infection still poses public health concerns. Many cases of resistance and cross-resistance are observed. Diagnosis by culture, which is considered as the standard method, takes too long (20-30days) and is not suitable for extrapulmonary TB. QuantiFERON test, which is an indirect immunoassay based on blood, was developed. Much hope was placed in this new approach because it is based on blood, and many research teams have used it. We discuss the results of these different research groups who have used QuantiFERON for diagnosis, prediction of disease progression, or monitoring patients during the treatment of TB. Articles published in PubMed and documents published on Google were searched with the keywords: diagnosis and TB and QuantiFERON; TB and QuantiFERON and therapeutic monitoring; interferon-γ release assay; disease progression. These articles were read and analyzed. The results were controversial with regards to using the QuantiFERON test for the diagnosis of TB according to the study population (ethnic group, bacillus Calmette-Guérin vaccine use) and according to the state of the immune system of the people studied (human immunodeficiency virus immunosuppression in cancer medication, hypertension). Also, research findings were controversial with regards to using QuantiFERON for monitoring TB patients on anti-TB medications. Also, the predictive positive value for the progression to TB among immigrant close contacts of both interferon-γ release assays was not better than that of the tuberculin skin test. The QuantiFERON has advantages and limitations depending on the type of population studied. Recommendations are made to improve the sensitivity and specificity and to differentiate between latent and active TB by adding other specific proteins in the Mycobacterium tuberculosis antigen cocktail. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Generic protease detection technology for monitoring periodontal disease.

PubMed

Zheng, Xinwei; Cook, Joseph P; Watkinson, Michael; Yang, Shoufeng; Douglas, Ian; Rawlinson, Andrew; Krause, Steffi

2011-01-01

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.

Toward surface quantification of liver fibrosis progression

NASA Astrophysics Data System (ADS)

He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

2010-09-01

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

Short-term ecological consequences of collaborative restoration treatments in ponderosa pine forests of Colorado

USGS Publications Warehouse

Briggs, Jenny S.; Fornwalt, Paula J.; Feinstein, Jonas A.

2017-01-01

Ecological restoration treatments are being implemented at an increasing rate in ponderosa pine and other dry conifer forests across the western United States, via the USDA Forest Service’s Collaborative Forest Landscape Restoration (CFLR) program. In this program, collaborative stakeholder groups work with National Forests (NFs) to adaptively implement and monitor ecological restoration treatments intended to offset the effects of many decades of anthropogenic stressors. We initiated a novel study to expand the scope of treatment effectiveness monitoring efforts in one of the first CFLR landscapes, Colorado’s Front Range. We used a Before/After/Control/Impact framework to evaluate the short-term consequences of treatments on numerous ecological properties. We collected pre-treatment and one year post-treatment data on NF and partner agencies’ lands, in 66 plots distributed across seven treatment units and nearby untreated areas. Our results reflected progress toward several treatment objectives: treated areas had lower tree density and basal area, greater openness, no increase in exotic understory plants, no decrease in native understory plants, and no decrease in use by tree squirrels and ungulates. However, some findings suggested the need for adaptive modification of both treatment prescriptions and monitoring protocols: treatments did not promote heterogeneity of stand structure, and monitoring methods may not have been robust enough to detect changes in surface fuels. Our study highlights both the effective aspects of these restoration treatments, and the importance of initiating and continuing collaborative science-based monitoring to improve the outcomes of broad-scale forest restoration efforts.

Volumetric optoacoustic monitoring of endovenous laser treatments

NASA Astrophysics Data System (ADS)

Fehm, Thomas F.; Deán-Ben, Xosé L.; Schaur, Peter; Sroka, Ronald; Razansky, Daniel

2016-03-01

Chronic venous insufficiency (CVI) is one of the most common medical conditions with reported prevalence estimates as high as 30% in the adult population. Although conservative management with compression therapy may improve the symptoms associated with CVI, healing often demands invasive procedures. Besides established surgical methods like vein stripping or bypassing, endovenous laser therapy (ELT) emerged as a promising novel treatment option during the last 15 years offering multiple advantages such as less pain and faster recovery. Much of the treatment success hereby depends on monitoring of the treatment progression using clinical imaging modalities such as Doppler ultrasound. The latter however do not provide sufficient contrast, spatial resolution and three-dimensional imaging capacity which is necessary for accurate online lesion assessment during treatment. As a consequence, incidence of recanalization, lack of vessel occlusion and collateral damage remains highly variable among patients. In this study, we examined the capacity of volumetric optoacoustic tomography (VOT) for real-time monitoring of ELT using an ex-vivo ox foot model. ELT was performed on subcutaneous veins while optoacoustic signals were acquired and reconstructed in real-time and at a spatial resolution in the order of 200μm. VOT images showed spatio-temporal maps of the lesion progression, characteristics of the vessel wall, and position of the ablation fiber's tip during the pull back. It was also possible to correlate the images with the temperature elevation measured in the area adjacent to the ablation spot. We conclude that VOT is a promising tool for providing online feedback during endovenous laser therapy.

Management of Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

PubMed Central

Silver, Katherine Culp

2015-01-01

Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests (PFTs) and high resolution CT (HRCT) scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. While immunosuppression remains the mainstay of treatment, anti-fibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future. PMID:26210128

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer.

PubMed

Sefrioui, David; Perdrix, Anne; Sarafan-Vasseur, Nasrin; Dolfus, Claire; Dujon, Antoine; Picquenot, Jean-Michel; Delacour, Julien; Cornic, Marie; Bohers, Elodie; Leheurteur, Marianne; Rigal, Olivier; Tennevet, Isabelle; Thery, Jean-Christophe; Alexandru, Cristina; Guillemet, Cécile; Moldovan, Cristian; Veyret, Corinne; Frebourg, Thierry; Di Fiore, Frédéric; Clatot, Florian

2015-11-15

Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a marker of resistance to aromatase inhibitors in hormone receptor positive metastatic breast cancer. We retrospectively considered seven patients treated for metastatic breast cancer with available samples from the primary tumor before any treatment, cryopreserved metastasis removed during progression and concomitant plasmas. All these seven patients were in disease progression after previous exposure to aromatase inhibitors for at least 6 months, and were assessed for ESR1 mutations detection in tumor and circulating DNA. For these patients, Sanger sequencing identified four metastases with clear ESR1 mutation and one possible, whereas digital PCR identified six mutated metastases. Then, under blind conditions and using digital PCR, corresponding circulating ESR1 mutations were successfully detected in four of these six metastatic breast cancer patients. Moreover, in two patients with serial blood samples following treatments exposure, the monitoring of circulating ESR1 mutations clearly predicted disease evolution. In the context of high interest for ESR1 mutations, our results highlight that these acquired recurrent mutations may be tracked in circulating tumor DNA and may be of clinical relevance for metastatic breast cancer patient monitoring. © 2015 UICC.

Increasing Psychotherapists’ Adoption and Implementation of the Evidence-based Practice of Progress Monitoring

PubMed Central

Persons, Jacqueline B.; Koerner, Kelly; Eidelman, Polina; Thomas, Cannon; Liu, Howard

2015-01-01

Evidence-based practices (EBPs) reach consumers slowly because practitioners are slow to adopt and implement them. We hypothesized that giving psychotherapists a tool + training intervention that was designed to help the therapist integrate the EBP of progress monitoring into his or her usual way of working would be associated with adoption and sustained implementation of the particular progress monitoring tool we trained them to use (the Depression Anxiety Stress Scales on our Online Progress Tracking tool) and would generalize to all types of progress monitoring measures. To test these hypotheses, we developed an online progress monitoring tool and a course that trained psychotherapists to use it, and we assessed progress monitoring behavior in 26 psychotherapists before, during, immediately after, and 12 months after they received the tool and training. Immediately after receiving the tool + training intervention, participants showed statistically significant increases in use of the online tool and of all types of progress monitoring measures. Twelve months later, participants showed sustained use of any type of progress monitoring measure but not the online tool. PMID:26618237

Increasing psychotherapists' adoption and implementation of the evidence-based practice of progress monitoring.

PubMed

Persons, Jacqueline B; Koerner, Kelly; Eidelman, Polina; Thomas, Cannon; Liu, Howard

2016-01-01

Evidence-based practices (EBPs) reach consumers slowly because practitioners are slow to adopt and implement them. We hypothesized that giving psychotherapists a tool + training intervention that was designed to help the therapist integrate the EBP of progress monitoring into his or her usual way of working would be associated with adoption and sustained implementation of the particular progress monitoring tool we trained them to use (the Depression Anxiety Stress Scales on our Online Progress Tracking tool) and would generalize to all types of progress monitoring measures. To test these hypotheses, we developed an online progress monitoring tool and a course that trained psychotherapists to use it, and we assessed progress monitoring behavior in 26 psychotherapists before, during, immediately after, and 12 months after they received the tool and training. Immediately after receiving the tool + training intervention, participants showed statistically significant increases in use of the online tool and of all types of progress monitoring measures. Twelve months later, participants showed sustained use of any type of progress monitoring measure but not the online tool. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress.

PubMed

Braconi, Daniela; Bernardini, Giulia; Paffetti, Alessandro; Millucci, Lia; Geminiani, Michela; Laschi, Marcella; Frediani, Bruno; Marzocchi, Barbara; Santucci, Annalisa

2016-12-01

Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fully automated disease severity assessment and treatment monitoring in retinopathy of prematurity using deep learning

NASA Astrophysics Data System (ADS)

Brown, James M.; Campbell, J. Peter; Beers, Andrew; Chang, Ken; Donohue, Kyra; Ostmo, Susan; Chan, R. V. Paul; Dy, Jennifer; Erdogmus, Deniz; Ioannidis, Stratis; Chiang, Michael F.; Kalpathy-Cramer, Jayashree

2018-03-01

Retinopathy of prematurity (ROP) is a disease that affects premature infants, where abnormal growth of the retinal blood vessels can lead to blindness unless treated accordingly. Infants considered at risk of severe ROP are monitored for symptoms of plus disease, characterized by arterial tortuosity and venous dilation at the posterior pole, with a standard photographic definition. Disagreement among ROP experts in diagnosing plus disease has driven the development of computer-based methods that classify images based on hand-crafted features extracted from the vasculature. However, most of these approaches are semi-automated, which are time-consuming and subject to variability. In contrast, deep learning is a fully automated approach that has shown great promise in a wide variety of domains, including medical genetics, informatics and imaging. Convolutional neural networks (CNNs) are deep networks which learn rich representations of disease features that are highly robust to variations in acquisition and image quality. In this study, we utilized a U-Net architecture to perform vessel segmentation and then a GoogLeNet to perform disease classification. The classifier was trained on 3,000 retinal images and validated on an independent test set of patients with different observed progressions and treatments. We show that our fully automated algorithm can be used to monitor the progression of plus disease over multiple patient visits with results that are consistent with the experts' consensus diagnosis. Future work will aim to further validate the method on larger cohorts of patients to assess its applicability within the clinic as a treatment monitoring tool.

Predicting reading outcomes with progress monitoring slopes among middle grade students

PubMed Central

Tolar, Tammy D.; Barth, Amy E.; Fletcher, Jack M.; Francis, David J.; Vaughn, Sharon

2013-01-01

Effective implementation of response-to-intervention (RTI) frameworks depends on efficient tools for monitoring progress. Evaluations of growth (i.e., slope) may be less efficient than evaluations of status at a single time point, especially if slopes do not add to predictions of outcomes over status. We examined progress monitoring slope validity for predicting reading outcomes among middle school students by evaluating latent growth models for different progress monitoring measure-outcome combinations. We used multi-group modeling to evaluate the effects of reading ability, reading intervention, and progress monitoring administration condition on slope validity. Slope validity was greatest when progress monitoring was aligned with the outcome (i.e., word reading fluency slope was used to predict fluency outcomes in contrast to comprehension outcomes), but effects varied across administration conditions (viz., repeated reading of familiar vs. novel passages). Unless the progress monitoring measure is highly aligned with outcome, slope may be an inefficient method for evaluating progress in an RTI context. PMID:24659899

[Remote sensing monitoring and screening for urban black and odorous water body: A review.

PubMed

Shen, Qian; Zhu, Li; Cao, Hong Ye

2017-10-01

Continuous improvement of urban water environment and overall control of black and odorous water body are not merely national strategic needs with the action plan for prevention and treatment of water pollution, but also the hot issues attracting the attention of people. Most previous researches concentrated on the study of cause, evaluation and treatment measures of this phenomenon, and there are few researches on the monitoring using remote sensing, which is often a strain to meet the national needs of operational monitoring. This paper mainly summarized the urgent research problems, mainly including the identification and classification standard, research on the key technologies, and the frame of remote sensing screening systems for the urban black and odorous water body. The main key technologies were concluded too, including the high spatial resolution image preprocessing and extraction technique for black and odorous water body, the extraction of water information in city zones, the classification of the black and odorous water, and the identification and classification technique based on satellite-sky-ground remote sensing. This paper summarized the research progress and put forward research ideas of monitoring and screening urban black and odorous water body via high spatial resolution remote sensing technology, which would be beneficial to having an overall grasp of spatial distribution and improvement progress of black and odorous water body, and provide strong technical support for controlling urban black and odorous water body.

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

PubMed

Hamdy, Freddie C; Donovan, Jenny L; Lane, J Athene; Mason, Malcolm; Metcalfe, Chris; Holding, Peter; Davis, Michael; Peters, Tim J; Turner, Emma L; Martin, Richard M; Oxley, Jon; Robinson, Mary; Staffurth, John; Walsh, Eleanor; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Paul, Alan; Powell, Philip; Prescott, Stephen; Rosario, Derek J; Rowe, Edward; Neal, David E

2016-10-13

The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Radiation necrosis presenting as pseudoprogression (PsP) during alectinib treatment of previously radiated brain metastases in ALK-positive NSCLC: Implications for disease assessment and management.

PubMed

Ou, Sai-Hong Ignatius; Klempner, Samuel J; Azada, Michele C; Rausei-Mills, Veronica; Duma, Christopher

2015-06-01

Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Curriculum-Based Measurement of Oral Reading: Quality of Progress Monitoring Outcomes

ERIC Educational Resources Information Center

Christ, Theodore J.; Zopluoglu, Cengiz; Long, Jeffery D.; Monaghen, Barbara D.

2012-01-01

Curriculum-based measurement of oral reading (CBM-R) is frequently used to set student goals and monitor student progress. This study examined the quality of growth estimates derived from CBM-R progress monitoring data. The authors used a linear mixed effects regression (LMER) model to simulate progress monitoring data for multiple levels of…

Biological markers of human tumors and monitoring of cancer treatment.

PubMed

Tanneberger, S; Nissen, E; Ziegenbein, R

1979-01-01

The development of human tumors is accompanied very often by tumor-associated phenomena such as production of tumor-derived substances, production of certian substances in response to the tumor or immunological reactions. Up to now no of these phenomena can be used as a diagnostic cancer test but biological markers are increasingly used for monitoring progression and regression of human tumors. Basing on a number of own studies the value of the determination of CEA-serum level and urinary excretion of hydroxyprolin, spermidin and putrescin for monitoring the tumor behaviour particularly during cancer chemotherapy is demonstrated.

Progression of Ulcerative Dermatitis Lesions in C57BL/6Crl Mice and the Development of a Scoring System for Dermatitis Lesions

PubMed Central

Hampton, Anna L; Hish, Gerald A; Aslam, Muhammad N; Rothman, Edward D; Bergin, Ingrid L; Patterson, Kathleen A; Naik, Madhav; Paruchuri, Tejaswi; Varani, James; Rush, Howard G

2012-01-01

Ulcerative dermatitis (UD) is a common, spontaneous condition in mice with a C57BL/6 background. Although initial lesions may be mild, UD is a progressive disease that often results in ulcerations or debilitating fibrotic contractures. In addition, lesions typically are unresponsive to treatment. Euthanasia is often warranted in severe cases, thereby affecting study outcomes through the loss of research subjects. Because the clinical assessment of UD can be subjective, a quantitative scoring method and documentation of the likely time-frame of progression may be helpful in predicting when animals that develop dermatitis should be removed from a study. Such a system may also be helpful in quantitatively assessing success of various treatment strategies and be valuable to clinical laboratory animal veterinarians. In this 1.5-y, prospective cohort study, we followed 200 mice to monitor the development and course of UD. Mice were examined every 2 wk. A clinical sign (alopecia, pruritus, or peripheral lymphadenopathy) was not identified that predicted development of UD lesions in the subsequent 2-wk period. Once UD developed, pruritus, the character of the lesion (single or multiple crust, coalescing crust, erosion, or ulceration), and the size of the lesion were the only parameters that changed (increased) over the course of the disease. Pruritus was a factor in the rapid progression of UD lesions. We used these findings to develop a quantitative scoring system for the severity of UD. This enhanced understanding of the progression of UD and the quantitative scoring system will enhance the monitoring of UD. PMID:23312087

Multimodal imaging-monitored progression of stroke-like episodes in a case of MELAS syndrome.

PubMed

Namer, Izzie Jacques; Wolff, Valérie; Dietemann, Jean-Louis; Marescaux, Christian

2014-03-01

We report imaging findings during, between, and after 2 stroke-like episodes in a 45-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome with an A32243G mitochondrial mutation 6 years before. In November 2010, for a first episode, she showed mixed aphasia with logorrhea, disinhibition, agitation, euphoria, and a large left temporoparietal lesion. Symptomatology progressively regressed under L-arginine treatment. She was readmitted in June 2011 for a second episode with great anxiety, disorientation, impaired face recognition, worsening mixed aphasia, and a new right temporal lesion. After additional L-carnitine treatment, she remained without relapse for 14 months.

Natural History of Rotator Cuff Disease and Implications on Management

PubMed Central

Hsu, Jason

2015-01-01

Degenerative rotator cuff disease is commonly associated with ageing and is often asymptomatic. The factors related to tear progression and pain development are just now being defined through longitudinal natural history studies. The majority of studies that follow conservatively treated painful cuff tears or asymptomatic tears that are monitored at regular intervals show slow progression of tear enlargement and muscle degeneration over time. These studies have highlighted greater risks for disease progression for certain variables, such as the presence of a full-thickness tear and involvement of the anterior aspect supraspinatus tendon. Coupling the knowledge of the natural history of degenerative cuff tear progression with variables associated with greater likelihood of successful tendon healing following surgery will allow better refinement of surgical indications for rotator cuff disease. In addition, natural history studies may better define the risks of nonoperative treatment over time. This article will review pertinent literature regarding degenerative rotator cuff disease with emphasis on variables important to defining appropriate initial treatments and refining surgical indications. PMID:26726288

Alzheimer's Dye Test?

ERIC Educational Resources Information Center

Science Teacher, 2005

2005-01-01

Massachusetts Institute of Technology (MIT) scientists have developed a new dye that could offer noninvasive early diagnosis of Alzheimer's disease, a discovery that could aid in monitoring the progression of the disease and in studying the efficacy of new treatments to stop it. The work is published in Angewandte Chemie. Today, doctors can only…

Dynamic Assessment in Phonological Disorders: The Scaffolding Scale of Stimulability

ERIC Educational Resources Information Center

Glaspey, Amy M.; Stoel-Gammon, Carol

2005-01-01

Dynamic assessment is applied to phonological disorders with the Scaffolding Scale of Stimulability (SSS). The SSS comprises a 21-point hierarchical scale of cues and linguistic environments. With the SSS, clinicians assess stimulability as a diagnostic indicator and use the measure to monitor progress across treatment. Unlike other phonological…

[Homeostasis and Disorder of Musculoskeletal System.Progress in the treatment of rheumatoid arthritis.

PubMed

Tanaka, Yoshiya

Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis. Clinical remission is now realistic targets for the treatment, achieved by a large proportion of rheumatoid arthritis patients, which leads to structural remission without damage in bone and cartilage as well as functional remission. Furthermore, orally available small but strong molecules targeting Janus kinase(JAK)are emerging. When DMARDs are prescribed, appropriate selection of DMARDs, adequate screening, regular monitoring and systemic management are required.

TREATMENT OF PROGRESSION OF DIFFUSE ASTROCYTOMA BY HERBAL MEDICINE: CASE REPORT.

PubMed

Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

2016-01-01

The paper presents the results of the use of phytotherapy in a 33-year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression. Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which the subject was taking in form of tea once a day at regular intervals. The patient started phytotherapy along with temozolomide, which was the only oncological treatment she was under after the tumour had progressed. Following the finished chemotherapy, the patient continued the treatment with herbal medicine only. She regularly took phytotherapy without interruption and to the fullest extent for 30 months, and the results of treatment were monitored by periodic scanning using nuclear magnetic resonance technique. The control scanning that was conducted after the end of combined treatment with temozolomide and phytotherapy showed tumour regression. The patient continued with phytotherapy after finishing chemotherapy and, during the following 24 months, it was the sole treatment option. In that period, the regression of the tumour continued, until a control examination 30 months after the introduction of phytotherapy showed no clinical and radiological signs of tumour. The results presented in this research paper clearly indicate the potential of phytotherapy in the treatment of some types of brain tumours. A complete regression of tumour following the treatment with nothing but herbal medicine offers support for such claim. Future research should demonstrate the effectiveness of phytotherapy, as a supplementary form of brain tumour treatment, and the results of this research should be compared with the existing information on the effectiveness of the protocols currently used in the treatment of these types of tumour.

Clinical utility of circulating tumour cell detection in non-small-cell lung cancer.

PubMed

Fusi, Alberto; Metcalf, Robert; Krebs, Matthew; Dive, Caroline; Blackhall, Fiona

2013-12-01

Recent years have witnessed increased interest in the detection of circulating tumour cells (CTCs) for diagnosis, monitoring, and treatment decision making in patients with cancer. Factors that have led to accelerated research in this field include advances in technologies for examination of intact CTCs, personalised medicine with treatment selection according to molecular characteristics, and continued lack of understanding of the biology of treatment resistance and metastasis. CTCs offer promise as a surrogate for tissue where there is insufficient tissue for molecular analysis and where there is a requirement to serially monitor molecular changes in cancer cells through treatment or on progression. In patients with either small cell or non-small cell lung cancer (NSCLC), there is evidence that CTC number is prognostic and that CTCs counted before and after treatment mirror treatment response. In patients with molecularly defined subtypes of NSCLC, CTCs demonstrate the same molecular changes as the cancer cells of the tumour. However, CTCs are not quite ready for "primetime" in the lung cancer clinic. There are still more questions than answers with respect to the optimal technologies for their detection and analysis, their biological significance, and their clinical utility. Despite this the current pace of progress in CTC technology development seems set to make "liquid biopsies" a clinical reality within the next decade. For the everyday clinician and clinical trialist, it will be important to maintain knowledge of the strengths and weaknesses of the technologies and evolving evidence base for CTCs as a routinely used diagnostic tool.

Flex Sensor Based Biofeedback Monitoring for Post-Stroke Fingers Myopathy Patients

NASA Astrophysics Data System (ADS)

Garda, Y. R.; Caesarendra, W.; Tjahjowidodo, T.; Turnip, A.; Wahyudati, S.; Nurhasanah, L.; Sutopo, D.

2018-04-01

Hands are one of the crucial parts of the human body in carrying out daily activities. Accidents on the hands decreasing in motor skills of the hand so that therapy is necessary to restore motor function of the hand. In addition to accidents, hand disabilities can be caused by certain diseases, e.g. stroke. Stroke is a partial destruction of the brain. It occurs if the arteries that drain blood to the brain are blocked, or if torn or leak. The purpose of this study to make biofeedback monitoring equipment for post-stroke hands myopathy patients. Biofeedback is an alternative method of treatment that involves measuring body functions measured subjects such as skin temperature, sweat activity, blood pressure, heart rate and hand paralysis due to stroke. In this study, the sensor used for biofeedback monitoring tool is flex sensor. Flex sensor is a passive resistive device that changes its resistance as the sensor is bent. Flex sensor converts the magnitude of the bend into electrical resistance, the greater the bend the greater the resistance value. The monitoring used in this biofeedback monitoring tool uses Graphical User Interface (GUI) in C# programming language. The motivation of the study is to monitor and record the progressive improvement of the hand therapy. Patients who experienced post-stroke can see the therapy progress quantitatively.

Apomab, a fully human agonistic antibody to DR5, exhibits potent antitumor activity against primary and metastatic breast cancer

PubMed Central

Zinonos, Irene; Labrinidis, Agatha; Lee, Michelle; Liapis, Vasilios; Hay, Shelley; Ponomarev, Vladimir; Diamond, Peter; Zannettino, Andrew C.W.; Findlay, David M.; Evdokiou, Andreas

2017-01-01

Apomab, a fully human agonistic DR5 monoclonal antibody, triggers apoptosis through activation of the extrinsic apoptotic signaling pathway. In this study, we assessed the cytotoxic effect of Apomab in vitro and evaluated its antitumor activity in murine models of breast cancer development and progression. MDA-MB-231-TXSA breast cancer cells were transplanted into the mammary fat pad or directly into the tibial marrow cavity of nude mice. Apomab was administered early, postcancer cell transplantation, or after tumors progressed to an advanced stage. Tumor burden was monitored progressively using bioluminescence imaging, and the development of breast cancer–induced osteolysis was measured using micro-computed tomography. In vitro, Apomab treatment induced apoptosis in a panel of breast cancer cell lines but was without effect on normal human primary osteoblasts, fibroblasts, or mammary epithelial cells. In vivo, Apomab exerted remarkable tumor suppressive activity leading to complete regression of well-advanced mammary tumors. All animals transplanted with breast cancer cells directly into their tibiae developed large osteolytic lesions that eroded the cortical bone. In contrast, treatment with Apomab following an early treatment protocol inhibited both intraosseous and extraosseous tumor growth and prevented breast cancer–induced osteolysis. In the delayed treatment protocol, Apomab treatment resulted in the complete regression of advanced tibial tumors with progressive restoration of both trabecular and cortical bone leading to full resolution of osteolytic lesions. Apomab represents a potent immunotherapeutic agent with strong activity against the development and progression of breast cancer and should be evaluated in patients with primary and metastatic disease. PMID:19808976

Effects of Progress Monitoring Feedback on Early Literacy Student Achievement

ERIC Educational Resources Information Center

Lopuch, Jeremy Jon

2016-01-01

The purpose of this study was to examine the effects of diagnostic formative assessment feedback on early literacy skills. The participants were 12 first-grade general education teachers and 51 of their students who were assigned to the following treatments, diagnostic feedback and skills feedback (control) which lasted for 10 weeks. During the…

Informant Discrepancies in Externalizing and Internalizing Symptoms and Adaptive Skills of High-Functioning Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

McDonald, Christin A.; Lopata, Christopher; Donnelly, James P.; Thomeer, Marcus L.; Rodgers, Jonathan D.; Jordan, Allyson K.

2016-01-01

Assessment of clinical symptoms requires information from multiple informants. Discrepancies between informants' ratings can have significant implications in school settings (e.g., access to services, treatment planning, progress monitoring). This study examined parent-teacher discrepancies for ratings of internalizing and externalizing symptoms,…

Common Progress Monitoring Graph Omissions: Missing Goal and Goal Line. Progress Monitoring Brief #2

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring assessment is one of the four essential components of Response to Intervention (RTI), as defined by the National Center on Response to Intervention (NCRTI). Progress data allow teachers to evaluate the academic performance of students over time, quantify rates of improvement or responsiveness to instruction, and evaluate…

Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

PubMed

Zhang, Wei; Xia, Wenjie; Lv, Zhengye; Ni, Chao; Xin, Yin; Yang, Liu

2017-01-01

Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional 'solid biopsy', which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning. © 2017 The Author(s)Published by S. Karger AG, Basel.

The neural basis of monitoring goal progress

PubMed Central

Benn, Yael; Webb, Thomas L.; Chang, Betty P. I.; Sun, Yu-Hsuan; Wilkinson, Iain D.; Farrow, Tom F. D.

2014-01-01

The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC) as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent functional magnetic resonance imagining (fMRI) while playing a game that involved monitoring progress toward either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory (WM) in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress toward a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring. PMID:25309380

Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque.

PubMed

Byrne, S J; Dashper, S G; Darby, I B; Adams, G G; Hoffmann, B; Reynolds, E C

2009-12-01

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with bacteria. Diagnosis is achieved retrospectively by clinical observation of attachment loss. Predicting disease progression would allow for targeted preventive therapy. The aim of this study was to monitor disease progression in patients on a maintenance program and determine the levels of specific bacteria in subgingival plaque samples and then examine the ability of the clinical parameters of disease and levels of specific bacteria in the plaque samples to predict disease progression. During a 12-month longitudinal study of 41 subjects, 25 sites in 21 subjects experienced disease progression indicated by at least 2 mm of clinical attachment loss. Real-time polymerase chain reaction was used to determine the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque samples. No clinical parameters were able to predict periodontal disease progression. In sites undergoing imminent periodontal disease progression within the next 3 months, significant partial correlations were found between P. gingivalis and T. forsythia (r = 0.55, P < 0.001) and T. denticola and T. forsythia (r = 0.43, P = 0.04). The odds of a site undergoing imminent periodontal disease progression increased with increasing levels of P. gingivalis and T. denticola. Monitoring the proportions of P. gingivalis and T. denticola in subgingival plaque has the potential to help identify sites at significant risk for progression of periodontitis, which would assist in the targeted treatment of disease.

Revolutionizing Child Welfare with Outcomes Management

PubMed Central

Toche-Manley, Linda L.; Dietzen, Laura; Nankin, Jesse; Beigel, Astrid

2013-01-01

Outcomes management technology holds great promise for improving the quality of services provided to youth in the child welfare system. Advantages include better detection of behavioral health and trauma-related issues, early indicators of case progress or risk of failure and program- and system-level learning. Yet organizational barriers to implementation persist. Attention is spent in this paper on addressing these barriers so the use of outcomes management technology becomes a common practice. A model for predicting resiliency is presented, along with case examples demonstrating its potential use for treatment planning and monitoring progress. PMID:23460130

Monitoring Transcriptomic Changes in Soil-Grown Roots and Shoots of Arabidopsis thaliana Subjected to a Progressive Drought Stress.

PubMed

Bashir, Khurram; Rasheed, Sultana; Matsui, Akihiro; Iida, Kei; Tanaka, Maho; Seki, Motoaki

2018-01-01

Numerous experiments have been performed in Arabidopsis to monitor changes in gene expression that occur in response to a variety of abiotic and biotic stresses, different growth conditions, and at various developmental stages. In addition, gene expression patterns have also been characterized among wild-type and mutant genotypes. Despite these numerous reports, transcriptional changes occurring in roots of soil-grown plants subjected to a progressive drought stress have remained undocumented. To fill this gap, we established a system that allows one to establish water-deficit conditions and to collect root and shoot samples with minimal damage to the root system. Arabidopsis plants are grown in a ceramic-based granular soil and subjected to progressive drought stress by withholding water. Root and shoot samples were collected separately, RNA was purified, and a microarray analysis of drought-stressed roots and shoots was performed at 0, 1, 3, 5, 7, and 9 days after the onset of drought stress treatment. Here, we describe the detailed protocol used to analyze the transcriptomic changes occurring in roots and shoots of soil-grown Arabidopsis subjected to a progressive drought stress.

Monitoring Academic and Social Skills in Elementary School: A Psychometric Evaluation of the Classroom Performance Survey

ERIC Educational Resources Information Center

Caldarella, Paul; Larsen, Ross A. A.; Williams, Leslie; Wehby, Joseph H.; Wills, Howard; Kamps, Debra

2017-01-01

Numerous well-validated academic progress monitoring tools are used in schools, but there are fewer behavioral progress monitoring measures available. Some brief behavior rating scales have been shown to be effective in monitoring students' progress, but most focus only on students' social skills and do not address critical academic-related…

Monitoring Academic and Social Skills in Elementary School: A Psychometric Evaluation of the Classroom Performance Survey

ERIC Educational Resources Information Center

Caldarella, Paul; Larsen, Ross A. A.; Williams, Leslie; Wehby, Joseph H.; Wills, Howard P.; Kamps, Debra M.

2017-01-01

Numerous well validated academic progress monitoring tools are used in schools, but there are fewer behavioral progress monitoring measures available. Some brief behavior rating scales have been shown to be effective in monitoring students' progress, but most focus only on students' social skills and do not address critical academic-related…

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Remote Blood Glucose Monitoring in mHealth Scenarios: A Review.

PubMed

Lanzola, Giordano; Losiouk, Eleonora; Del Favero, Simone; Facchinetti, Andrea; Galderisi, Alfonso; Quaglini, Silvana; Magni, Lalo; Cobelli, Claudio

2016-11-24

Glucose concentration in the blood stream is a critical vital parameter and an effective monitoring of this quantity is crucial for diabetes treatment and intensive care management. Effective bio-sensing technology and advanced signal processing are therefore of unquestioned importance for blood glucose monitoring. Nevertheless, collecting measurements only represents part of the process as another critical task involves delivering the collected measures to the treating specialists and caregivers. These include the clinical staff, the patient's significant other, his/her family members, and many other actors helping with the patient treatment that may be located far away from him/her. In all of these cases, a remote monitoring system, in charge of delivering the relevant information to the right player, becomes an important part of the sensing architecture. In this paper, we review how the remote monitoring architectures have evolved over time, paralleling the progress in the Information and Communication Technologies, and describe our experiences with the design of telemedicine systems for blood glucose monitoring in three medical applications. The paper ends summarizing the lessons learned through the experiences of the authors and discussing the challenges arising from a large-scale integration of sensors and actuators.

Remote Blood Glucose Monitoring in mHealth Scenarios: A Review

PubMed Central

Lanzola, Giordano; Losiouk, Eleonora; Del Favero, Simone; Facchinetti, Andrea; Galderisi, Alfonso; Quaglini, Silvana; Magni, Lalo; Cobelli, Claudio

2016-01-01

Glucose concentration in the blood stream is a critical vital parameter and an effective monitoring of this quantity is crucial for diabetes treatment and intensive care management. Effective bio-sensing technology and advanced signal processing are therefore of unquestioned importance for blood glucose monitoring. Nevertheless, collecting measurements only represents part of the process as another critical task involves delivering the collected measures to the treating specialists and caregivers. These include the clinical staff, the patient’s significant other, his/her family members, and many other actors helping with the patient treatment that may be located far away from him/her. In all of these cases, a remote monitoring system, in charge of delivering the relevant information to the right player, becomes an important part of the sensing architecture. In this paper, we review how the remote monitoring architectures have evolved over time, paralleling the progress in the Information and Communication Technologies, and describe our experiences with the design of telemedicine systems for blood glucose monitoring in three medical applications. The paper ends summarizing the lessons learned through the experiences of the authors and discussing the challenges arising from a large-scale integration of sensors and actuators. PMID:27886122

Current perspective of neuroprotection and glaucoma

PubMed Central

Tian, Kailin; Shibata-Germanos, Shannon; Pahlitzsch, Milena; Cordeiro, M Francesca

2015-01-01

Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs). The main concomitant factor is the elevated intraocular pressure (IOP). Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment. PMID:26635467

Quantitative long term measurements of burns in a rat model using Spatial Frequency Domain Imaging (SFDI) and Laser Speckle Imaging (LSI)

PubMed Central

Ponticorvo, Adrien; Burmeister, David M.; Rowland, Rebecca; Baldado, Melissa; Kennedy, Gordon T.; Saager, Rolf; Bernal, Nicole; Choi, Bernard; Durkin, Anthony J.

2017-01-01

The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies are shifting focus to burn care in an attempt to help quantify not only burn depth but also the progress of healing. While accurate early assessment of partial thickness burns is critical for dictating the course of treatment, the ability to quantitatively monitor wound status over time is critical for understanding treatment efficacy. SFDI and LSI are both non-invasive imaging modalities that have been shown to have great diagnostic value for burn severity, but have yet to be tested over the course of wound healing. In this study, a hairless rat model (n=6, 300-450g) was used with a four pronged comb to create four identical partial thickness burns (superficial n=3 and deep n=3) that were used to monitor wound healing over a 28 day period. Weekly biopsies were taken for histological analysis to verify wound progression. Both SFDI and LSI were performed weekly to track the evolution of hemodynamic (blood flow and oxygen saturation) and structural (reduced scattering coefficient) properties for the burns. LSI showed significant changes in blood flow from baseline to 220% in superficial and 165% in deep burns by day 7. In superficial burns, blood flow returned to baseline levels by day 28, but not for deep burns where blood flow remained elevated. Smaller increases in blood flow were also observed in the surrounding tissue over the same time period. Oxygen saturation values measured with SFDI showed a progressive increase from baseline values of 66% to 74% in superficial burns and 72% in deep burns by day 28. Additionally, SFDI showed significant decreases in the reduced scattering coefficient shortly after the burns were created. The scattering coefficient progressively decreased in the wound area, but returned towards baseline conditions at the end of the 28 day period. Scattering changes in the surrounding tissue remained constant despite the presence of hemodynamic changes. Here we show that LSI and SFDI are capable of monitoring changes in hemodynamic and scattering properties in burn wounds over a 28 day period. These results highlight the potential insights that can be gained by using noninvasive imaging technologies to study wound healing. Further development of these technologies could be revolutionary for wound monitoring and studying the efficacy of different treatments. PMID:28220508

Evaluation of the Effects of Sensory Integration-Based Intervention by a Preschool Special Education Teacher

ERIC Educational Resources Information Center

Bonggat, Penelope Wong; Hall, Laura J.

2010-01-01

This study addresses the call for increased research on common public school practices and progress monitoring by public school teachers. An alternating treatment design was implemented by a preschool teacher to evaluate the effect of sensory-integration based activities compared with an attention control on the on task behavior of three…

The Effects of Relaxation Training with Cognitive or Nondirective Therapy and the Role of Relaxation-Induced Anxiety in the Treatment of Generalized Anxiety.

ERIC Educational Resources Information Center

Borkovec, T. D.; And Others

1987-01-01

Provided 30 volunteers with generalized anxiety disorder with training in progressive muscle relaxation. Clients were also given cognitive or nondirective therapy. All showed substantial reductions in anxiety measured by psychiatric assessor ratings, questionnaires, and daily self-monitoring. Relaxation plus cognitive therapy produced…

[Is it too late to start orthopedic treatment for idiopathic scoliosis with Risser scores of 4?].

PubMed

Avellanet, M; González Viejo, M-A; Sáenz, A; Hijós, M-E

2006-12-01

Orthopaedic treatment for idiopathic scoliosis in adolescence is indicated with a curve of > or =20 degrees and a Risser score< or =4, because progression of curve is low with Risser scores >4. We present the case of a young man with a left lumbar idiopathic scoliosis (T12-L4) with a curve of 10 degrees, which was stable from 13 years (Risser 0) to 16 years old (Risser 4). The scoliosis progressed quickly after a Risser score of 4 was achieved. The man had been wearing a lift on the left foot since he was 13, because of a leg length discrepancy, and had been under clinical and radiological monitoring. When the boy reached 17 years, the scoliosis rapidly progressed, to a curve of 22 degrees and a Risser score of >4. The scoliosis was effectively treated with a Boston brace. At 20 years, the Risser score was 5, and the left lumbar curve was 13 degrees after discontinuing the use of the brace. To our knowledge, no scientific reference indicates a time limit to orthopaedic treatment for idiopathic adolescent scoliosis. Despite the experts' recommendations, a brace might be indicated with a Risser score > or =4 to stop the progression of the curve.

Design and implementation air quality monitoring robot

NASA Astrophysics Data System (ADS)

Chen, Yuanhua; Li, Jie; Qi, Chunxue

2017-01-01

Robot applied in environmental protection can break through the limitations in working environment, scope and mode of the existing environmental monitoring and pollution abatement equipments, which undertake the innovation and improvement in the basin, atmosphere, emergency and pollution treatment facilities. Actually, the relevant technology is backward with limited research and investment. Though the device companies have achieved some results in the study on the water quality monitoring, pipeline monitoring and sewage disposal, this technological progress on the whole is still much slow, and the mature product has not been formed. As a result, the market urges a demand of a new type of device which is more suitable for environmental protection on the basis of robot successfully applied in other fields. This paper designs and realizes a tracked mobile robot of air quality monitoring, which can be used to monitor air quality for the pollution accident in industrial parks and regular management.

Series length used during trend analysis affects sensitivity to changes in progression rate in the ocular hypertension treatment study.

PubMed

Gardiner, Stuart K; Demirel, Shaban; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Cioffi, George A; Ritch, Robert; Gordon, Mae O; Kass, Michael A

2013-02-15

Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability. Series of visual fields (mean 24 per eye) completed at 6-month intervals from participants randomized initially to observation were split into subseries before and after the initiation of treatment (the "split-point"). The mean deviation rate of change (MDR) was derived using these entire subseries, and using only the window length (W) tests nearest the split-point, for different window lengths of W tests. A generalized estimating equation model was used to detect changes in MDR occurring at the split-point. Using shortened subseries with W = 7 tests, the MDR slowed by 0.142 dB/y upon initiation of treatment (P < 0.001), and the proportion of eyes showing "rapid deterioration" (MDR <-0.5 dB/y with P < 5%) decreased from 11.8% to 6.5% (P < 0.001). Using the entire sequence, no significant change in MDR was detected (P = 0.796), and there was no change in the proportion of eyes progressing (P = 0.084). Window lengths 6 ≤ W ≤ 9 produced similar benefits. Event analysis revealed a beneficial treatment effect in this dataset. This effect was not detected by linear trend analysis applied to entire series, but was detected when using shorter subseries of length between six and nine fields. Using linear trend analysis on the entire field sequence may not be optimal for detecting and monitoring progression. Nonlinear analyses may be needed for long series of fields. (ClinicalTrials.gov number, NCT00000125.).

The effectiveness of anticellulite treatment using tripolar radiofrequency monitored by classic and high-frequency ultrasound.

PubMed

Mlosek, R K; Woźniak, W; Malinowska, S; Lewandowski, M; Nowicki, A

2012-06-01

  Cellulite affects nearly 85% of the female population. Given the size of the phenomenon, we are continuously looking for effective ways to reduce cellulite. Reliable monitoring of anticellulite treatment remains a problem.   The main aim of the study was to evaluate the effectiveness of anticellulite treatment carried out using radiofrequency (RF), which was monitored by classical and high-frequency ultrasound.   Twenty-eight women underwent anticellulite treatment using RF, 17 women were in the placebo group. The therapy was monitored by classical and high-frequency ultrasound. The examinations evaluated the thickness of the epidermal echo, dermis thickness, dermis echogenicity, the length of the subcutaneous tissue bands growing into the dermis, the presence or absence of oedema, the thickness of subcutaneous tissue as well as thigh circumference and the stage of cellulite (according to the Nürnberger-Müller scale).   Cellulite was reduced in 89.286% of the women who underwent RF treatment. After the therapy, the following observations were made: a decrease in the thickness of the dermis and subcutaneous tissue, an increase in echogenicity reflecting on the increase in the number of collagen fibres, decreased subcutaneous tissue growing into bands in the dermis, and the reduction of oedema. In the placebo group, no statistically significant changes of the above parameters were observed.   Radiofrequency enables cellulite reduction. A crucial aspect is proper monitoring of the progress of such therapy, which ultrasound allows. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Imaging in rheumatology: reconciling radiology and rheumatology.

PubMed

Tins, Bernhard J; Butler, Robin

2013-12-01

Imaging in rheumatology was in the past largely confined to radiographs of the hands and sacroiliac joints (SIJs) helping to establish the diagnosis and then monitoring disease progression. Radiographs are not very sensitive for early inflammation in inflammatory rheumatic disorders and the demand on imaging services was therefore limited. However, over the last 10-15 years new drugs and new technologies have brought new challenges and opportunities to rheumatology and radiology as specialties. New drug treatments allow more effective treatment, preventing many complications. Early diagnosis and disease monitoring has become the challenge for the rheumatologist and radiologist alike. The best possible patient outcome is only achieved if the two specialties understand each other's viewpoint. This article reviews the role of imaging-in particular radiography, magnet resonance imaging, computer tomography, ultrasound and nuclear medicine-for the diagnosis and monitoring of rheumatological disorders, concentrating on rheumatoid arthritis, inflammatory spondylarthropathies and gout. Teaching Points • New drugs for the treatment of inflammatory disorders has led to greatly improved outcomes. • Imaging often allows for earlier diagnosis of inflammatory disorders. • Early diagnosis and treatment can often prevent the development of crippling disease manifestations. • Tailored imaging examinations are best achieved by consultation of rheumatologist and radiologist.

Behavioral-Progress Monitoring Using the Electronic Daily Behavioral Report Card (e-DBRC) System

ERIC Educational Resources Information Center

Burke, Mack D.; Vannest, Kimberly J.

2008-01-01

In this article, the authors present an overview of a Web-based electronic system for behavioral-progress monitoring. Behavioral-progress monitoring is necessary to evaluate responsiveness to behavioral interventions, the effects of positive behavioral support, and the attainment of individualized education program goals and objectives. The…

Decision-Making Accuracy of CBM Progress-Monitoring Data

ERIC Educational Resources Information Center

Hintze, John M.; Wells, Craig S.; Marcotte, Amanda M.; Solomon, Benjamin G.

2018-01-01

This study examined the diagnostic accuracy associated with decision making as is typically conducted with curriculum-based measurement (CBM) approaches to progress monitoring. Using previously published estimates of the standard errors of estimate associated with CBM, 20,000 progress-monitoring data sets were simulated to model student reading…

Using an Online Tool for Learning about and Implementing Algebra Progress Monitoring

ERIC Educational Resources Information Center

Foegen, Anne; Stecker, Pamela M.; Genareo, Vincent R.; Lyons, Renée; Olson, Jeannette R.; Simpson, Amber; Romig, John Elwood; Jones, Rachel

2016-01-01

Research supports special educators' use of progress-monitoring data for instructional decision-making purposes as an evidence-based practice for improving student achievement. This article describes the Professional Development for Algebra Progress Monitoring (PD-APM) system. PD-APM, is an online system that includes two "hubs" that…

Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

PubMed Central

Martini, Andrea; Gallotta, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2015-01-01

Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. PMID:26689503

Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC.

PubMed

Knebel, Franciele H; Bettoni, Fabiana; Shimada, Andrea K; Cruz, Manoel; Alessi, João Victor; Negrão, Marcelo V; Reis, Luiz Fernando L; Katz, Artur; Camargo, Anamaria A

2017-06-01

Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation. Erlotinib was discontinued and osimertinib was initiated. Blood samples were collected at erlotinib progression and during osimertinib treatment for the detection of the activating (EGFR-exon19del) and resistance mutations (EGFR-T790M, EGFR-C797S, BRAF-V600E, METamp and ERBB2amp) in the plasma DNA using digital droplet PCR. Plasma levels of the activating EGFR-exon19del accurately paralleled the clinical and radiological progression of disease and allowed early detection of AR to osimertinib. Resistance to osimertinib coincided with the emergence of a small tumor cell subpopulation carrying the known EGFR-C797S resistance mutation and an additional subpopulation carrying amplified copies of EGFR-exon19del. Given the existence of multiple AR mechanisms, quantification of the original EGFR activation mutation, instead of the resistance mutations, can be efficiently used to monitor response to osimertinib, allowing early detection of AR. Absolute quantification of both activation and resistance mutations can provide important information on tumor clonal evolution upon progression to osimertinib. Selective amplification of the EGFR-exon19del allele may represent a novel resistance mechanism to osimertinib. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammatory mediators as biomarkers in brain disorders.

PubMed

Nuzzo, Domenico; Picone, Pasquale; Caruana, Luca; Vasto, Sonya; Barera, Annalisa; Caruso, Calogero; Di Carlo, Marta

2014-06-01

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases.

An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food

PubMed Central

Majdinasab, Marjan; Yaqub, Mustansara; Rahim, Abdur; Catanante, Gaelle; Hayat, Akhtar; Marty, Jean Louis

2017-01-01

Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food. PMID:28837093

Monitoring of the degradation in the rat's articular cartilage inducing osteoarthritis using common-path Fourier-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Shin, D. H.; Park, S. H.; Kim, B. Y.; Lee, M. Y.; Baik, H. K.; Seo, J. H.; Kang, J. U.; Song, C. G.

2013-03-01

The objective of this experiment is to evaluate the utility and limitations of optical coherence tomography (OCT) for real-time, high-resolution structural analysis. We monitored the degradation of the rat's articular cartilage inducing osteoarthritis (OA) and the change of the rat's articular cartilage recovery by treatment medication, using our developed common-path Fourier-domain (CP-FD) OCT. Also, we have done a comparative analysis the rat's articular cartilage and OA grade. To observe the progression of OA, we induced OA by injecting the monosodium iodoacetate (MIA) into the right knee joint. After the injection of MIA, we sacrificed the rats at intervals of 3 days and obtained OCT and histological images. OCT and histological images showed the OA progress of similar pattern. These results illustrated the potential for non-invasive diagnosis about the grade of OA using CP-FD OCT.

Orthodontic treatment effects on inflammatory marker profiles in saliva before and after 2 archwire changes

NASA Astrophysics Data System (ADS)

Yamamoto, Zulham; Jaafar, Ikmal Mohamad; Rohaya, M. A. W.; Abidin, Intan Zarina Zainol; Senafi, Sahidan; Ariffin, Zaidah Zainal; Ariffin, Shahrul Hisham Zainal

2013-11-01

Periodontal tissue changes exerted by external forces in orthodontic treatment allow tooth movement. The changes in periodontal tissues i.e. inflammation can be monitored using gingival crevicular fluid (GCF). GCF is a component of saliva. Saliva could be used to monitor periodontal disease progression. The use of saliva to monitor periodontal tissues changes during orthodontic treatment is still unknown. Therefore, we observed the profiles of inflammatory markers namely creatine kinase ('CK), nitric oxide (NO), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in saliva of orthodontic patients to evaluate their importance in orthodontic treatment. A total of 21 subjects (13 female and 8 male) participated in this study. Samples were collected from gingival crevicular fluid at three period of archwire changes: baseline (M0), 2 weeks after 0.014" NiTi archwire (M1), and 2 weeks after 0.018" NiTi archwire (M2). All enzyme activities i.e. CK, LDH and AST were measured spectrophotometrically at 340 nm. Griess assay was used to measure nitric oxide level. CK activity, NO level, LDH activity and AST activity in saliva samples did not show significant differences among period of archwire changes. The use of inflammatory marker profiles in saliva may not represent the changes in periodontal tissues during orthodontic treatment.

Biomarkers in the evolution of multiple sclerosis.

PubMed

Berger, Thomas

2017-11-01

Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown. Currently, there are no individualized biomarkers suitable to track disease progression. Neutralizing antibodies against IFN-β, natalizumab and daclizumab arise with variable frequency and reduce treatment efficacy. The anti-John Cunningham virus antibody index has potential as a biomarker for risk of progressive multifocal leukoencephalopathy.

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

PubMed

Mikhaylova, Irina N; Shubina, Irina Zh; Chkadua, George Z; Petenko, Natalia N; Morozova, Lidia F; Burova, Olga S; Beabelashvili, Robert Sh; Parsunkova, Kermen A; Balatskaya, Natalia V; Chebanov, Dmitrii K; Pospelov, Vadim I; Nazarova, Valeria V; Vihrova, Anastasia S; Cheremushkin, Evgeny A; Molodyk, Alvina A; Kiselevsky, Mikhail V; Demidov, Lev V

2018-05-11

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

Advanced Imaging in Osteoarthritis

PubMed Central

Li, Qi; Amano, Keiko; Link, Thomas M.; Ma, C. Benjamin

2016-01-01

Context: Radiography is widely accepted as the gold standard for diagnosing osteoarthritis (OA), but it has limitations when assessing early stage OA and monitoring progression. While there are improvements in the treatment of OA, the challenge is early recognition. Evidence Acquisition: MEDLINE and PubMed as well as professional orthopaedic and imaging websites were reviewed from 2006 to 2016. Study Design: Clinical review. Level of Evidence: Level 4. Results: Magnetic resonance imaging (MRI) can provide the most comprehensive assessment of joint injury and OA with the advantages of being noninvasive and multiplanar with excellent soft tissue contrast. However, MRI is expensive, time consuming, and not widely used for monitoring OA clinically. Computed tomography (CT) and CT arthrography (CTA) can also be used to evaluate OA, but these are also invasive and require radiation exposure. Ultrasound is particularly useful for evaluation of synovitis but not for progression of OA. Conclusion: MRI, CT, and CTA are available for the diagnosis and monitoring of OA. Improvement in techniques and decrease in cost can allow some of these modalities to be effective methods of detecting early OA. PMID:27510507

Common Progress Monitoring Omissions: Planning and Practice. Progress Monitoring Brief #1

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

MAPP (Monitoring Academic Progress Policy): Providing Advising Direction Through the Use of a Degree Auditing System.

ERIC Educational Resources Information Center

Severy, Lawrence J.; Slinger, Peter J.

1996-01-01

Describes a computerized partial degree auditing system, MAPP (Monitoring Academic Progress Policy), developed at the University of Florida to monitor students' progress into appropriate majors and apply institutional policy concerning degrees. The system generates letters directing students to advisors when needed. Discusses advantages for…

Common Progress Monitoring Omissions: Reporting Information to Parents. Progress Monitoring Brief #4

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Web-Based Mathematics Progress Monitoring in Second Grade

ERIC Educational Resources Information Center

Salaschek, Martin; Souvignier, Elmar

2014-01-01

We examined a web-based mathematics progress monitoring tool for second graders. The tool monitors the learning progress of two competences, number sense and computation. A total of 414 students from 19 classrooms in Germany were checked every 3 weeks from fall to spring. Correlational analyses indicate that alternate-form reliability was adequate…

Use of a Progress Monitoring System to Enable Teachers to Differentiate Mathematics Instruction

ERIC Educational Resources Information Center

Ysseldyke, Jim; Tardrew, Steve

2007-01-01

We explored how a progress monitoring and instructional management system can be used to help educators differentiate instruction and meet the wide-ranging learning needs of their increasingly diverse classrooms. We compared classrooms in 24 states that used a curriculum-based progress monitoring and instructional management system, Accelerated…

Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

PubMed

Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

2015-02-02

Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

Challenges in the management of glaucoma in developing countries.

PubMed

Butt, Nadeem Hafeez; Ayub, Muhammad Hammad; Ali, Muhammad Hassaan

2016-01-01

Glaucoma is the most common optic neuropathy characterized by normal to raised intraocular pressure (IOP), visual field defects, loss of retinal nerve fiber layer, thinning of the neuroretinal rim, and cupping of the optic disc. IOP reduction by medical, laser, or surgical therapies remains the only clinically proven treatment of glaucoma. The challenges in glaucoma management are diverse. They include early detection and diagnosis, setting of appropriate target IOP, choice of treatment, monitoring of quality of life and sight, and compliance with the treatment. Early diagnosis can be made by assessing optic nerve structure using imaging devices and optic nerve function through perimetry. Reducing IOP and controlling its fluctuations are considered to be the most important factors in limiting progression of glaucoma. Selection of the best suitable therapy out of medical, surgical, or laser treatment options is yet another management challenge. Patients suffering from glaucoma experience poor quality of life owing to the diagnosis itself, functional visual loss, inconvenience and cost of treatment, and side effects of treatment. All these factors lead to poor compliance, adherence, and persistence to treatment, and further progression of the disease. It is, therefore, important that ophthalmologists keep all the aforementioned factors in mind when managing patients with glaucoma.

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their

Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

PubMed Central

Nilsson, R. Jonas A.; Karachaliou, Niki; Berenguer, Jordi; Gimenez-Capitan, Ana; Schellen, Pepijn; Teixido, Cristina; Tannous, Jihane; Kuiper, Justine L.; Drees, Esther; Grabowska, Magda; van Keulen, Marte; Heideman, Danielle A.M.; Thunnissen, Erik; Dingemans, Anne-Marie C.; Viteri, Santiago; Tannous, Bakhos A.; Drozdowskyj, Ana; Rosell, Rafael; Smit, Egbert F.; Wurdinger, Thomas

2016-01-01

Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. PMID:26544515

Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer.

PubMed

Nilsson, R Jonas A; Karachaliou, Niki; Berenguer, Jordi; Gimenez-Capitan, Ana; Schellen, Pepijn; Teixido, Cristina; Tannous, Jihane; Kuiper, Justine L; Drees, Esther; Grabowska, Magda; van Keulen, Marte; Heideman, Danielle A M; Thunnissen, Erik; Dingemans, Anne-Marie C; Viteri, Santiago; Tannous, Bakhos A; Drozdowskyj, Ana; Rosell, Rafael; Smit, Egbert F; Wurdinger, Thomas

2016-01-05

Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.

Self-guided training for deep brain stimulation planning using objective assessment.

PubMed

Holden, Matthew S; Zhao, Yulong; Haegelen, Claire; Essert, Caroline; Fernandez-Vidal, Sara; Bardinet, Eric; Ungi, Tamas; Fichtinger, Gabor; Jannin, Pierre

2018-04-04

Deep brain stimulation (DBS) is an increasingly common treatment for neurodegenerative diseases. Neurosurgeons must have thorough procedural, anatomical, and functional knowledge to plan electrode trajectories and thus ensure treatment efficacy and patient safety. Developing this knowledge requires extensive training. We propose a training approach with objective assessment of neurosurgeon proficiency in DBS planning. To assess proficiency, we propose analyzing both the viability of the planned trajectory and the manner in which the operator arrived at the trajectory. To improve understanding, we suggest a self-guided training course for DBS planning using real-time feedback. To validate the proposed measures of proficiency and training course, two experts and six novices followed the training course, and we monitored their proficiency measures throughout. At baseline, experts planned higher quality trajectories and did so more efficiently. As novices progressed through the training course, their proficiency measures increased significantly, trending toward expert measures. We developed and validated measures which reliably discriminate proficiency levels. These measures are integrated into a training course, which quantitatively improves trainee performance. The proposed training course can be used to improve trainees' proficiency, and the quantitative measures allow trainees' progress to be monitored.

Chronic Diarrhea in Dogs: What Do We Actually Know About It?

PubMed

Westermarck, Elias

2016-06-01

There is a paucity of research based knowledge about chronic diarrhoea in dogs. In the literature no studies can be found that confirms that round worm, whip worm, hook worm or giardia cause chronic diarrhoea in dogs. For this reason, it is questionable to study endoparasites when clarifying the reason for chronic diarrhoea in dogs. No study confirms that clostridium-, campylobacter- or salmonella species cause chronic diarrhoea signs in dogs. There is no research-based information to-date that endoscopy would be helpful in the diagnosis of dogs with chronic diarrhoea or to monitor how the disease progresses. Neither no reliable laboratory test can be recommended to be used in evaluating the seriousness of the disease or to monitor the progress of the disease. There is no evidence based information on what food should be recommended for dogs suffering from diarrhoea. Only a few studies have been published that show how effective antibiotics are in the treatment of diarrhoeal dogs. Many more studies are needed before it is possible to determine how effective corticosteroids are in the treatment of diarrhoea in dogs. Copyright © 2016 Elsevier Inc. All rights reserved.

Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.

PubMed

Huang, Sharon K; Hoon, Dave S B

2016-03-01

Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post-treatment drug resistance often developed in melanoma patients. Non-invasive blood biomarker assays allow for regular dynamic monitoring of disease. "Liquid Biopsy" of blood, which exploits circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and cell-free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. With advancements of improving molecular assays, liquid biopsy analysis as a powerful, routine clinical assay for melanoma patients, is highly promising prospective. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Base-Position Error Rate Analysis of Next-Generation Sequencing Applied to Circulating Tumor DNA in Non-Small Cell Lung Cancer: A Prospective Study

PubMed Central

Zonta, Eleonora; Didelot, Audrey; Combe, Pierre; Thibault, Constance; Gibault, Laure; Lours, Camille; Taly, Valérie; Laurent-Puig, Pierre

2016-01-01

Background Circulating tumor DNA (ctDNA) is an approved noninvasive biomarker to test for the presence of EGFR mutations at diagnosis or recurrence of lung cancer. However, studies evaluating ctDNA as a noninvasive “real-time” biomarker to provide prognostic and predictive information in treatment monitoring have given inconsistent results, mainly due to methodological differences. We have recently validated a next-generation sequencing (NGS) approach to detect ctDNA. Using this new approach, we evaluated the clinical usefulness of ctDNA monitoring in a prospective observational series of patients with non-small cell lung cancer (NSCLC). Methods and Findings We recruited 124 patients with newly diagnosed advanced NSCLC for ctDNA monitoring. The primary objective was to analyze the prognostic value of baseline ctDNA on overall survival. ctDNA was assessed by ultra-deep targeted NGS using our dedicated variant caller algorithm. Common mutations were validated by digital PCR. Out of the 109 patients with at least one follow-up marker mutation, plasma samples were contributive at baseline (n = 105), at first evaluation (n = 85), and at tumor progression (n = 66). We found that the presence of ctDNA at baseline was an independent marker of poor prognosis, with a median overall survival of 13.6 versus 21.5 mo (adjusted hazard ratio [HR] 1.82, 95% CI 1.01–3.55, p = 0.045) and a median progression-free survival of 4.9 versus 10.4 mo (adjusted HR 2.14, 95% CI 1.30–3.67, p = 0.002). It was also related to the presence of bone and liver metastasis. At first evaluation (E1) after treatment initiation, residual ctDNA was an early predictor of treatment benefit as judged by best radiological response and progression-free survival. Finally, negative ctDNA at E1 was associated with overall survival independently of Response Evaluation Criteria in Solid Tumors (RECIST) (HR 3.27, 95% CI 1.66–6.40, p < 0.001). Study population heterogeneity, over-representation of EGFR-mutated patients, and heterogeneous treatment types might limit the conclusions of this study, which require future validation in independent populations. Conclusions In this study of patients with newly diagnosed NSCLC, we found that ctDNA detection using targeted NGS was associated with poor prognosis. The heterogeneity of lung cancer molecular alterations, particularly at time of progression, impairs the ability of individual gene testing to accurately detect ctDNA in unselected patients. Further investigations are needed to evaluate the clinical impact of earlier evaluation times at 1 or 2 wk. Supporting clinical decisions, such as early treatment switching based on ctDNA positivity at first evaluation, will require dedicated interventional studies. PMID:28027313

[Reliability of endocervical curettage after conservative treatment of intraepithelial neoplasia of the cervix].

PubMed

Lecointre, L; Akladios, C-Y; Averous, G; Lefebvre, F; Baulon, E; Thoma, V; Fender, M; Baldauf, J-J

2015-02-01

To evaluate the reliability of endocervical curettage (ECC) in patients previously treated for CIN. Retrospective analysis of data from 85 patients between January 1985 and December 2011 who received an ECC during monitoring after treatment of CIN. The reliability of the ECC was evaluated by comparison with the final histological analysis of the surgical specimen or the data for subsequent cyto-colpo-histological follow-up. Patients were referred to colposcopy either within the immediate post-treatment monitoring (n=42), meanly 9.7±5.3 months after treatment, or if cytological abnormalities were detected during long-term monitoring, meanly 78.6±52.4 months after treatment. Colposcopy was unsatisfactory in 75.3% of patients and normal colposcopic findings were found in 80% of patients. A perfect agreement between the ECC and the endocervical final diagnosis was noted in 68 patients (80%). For the diagnosis of severe cervical lesions (CIN 2+) ECC had a sensitivity of 86.2% (68.3-96.1), a specificity of 94.6% (85.1-98.9) and positive and negative predictive values of 61.4% (47.6-74.0) and 93% (83.0-98.1), respectively. The high sensitivity and negative predictive value of ECC for the diagnosis of severe post-therapeutic endocervical lesions avoid iterative treatment without increasing the risk of progression of a lesion to cancer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Introduction to biosensors

PubMed Central

Bhalla, Nikhil; Jolly, Pawan; Formisano, Nello

2016-01-01

Biosensors are nowadays ubiquitous in biomedical diagnosis as well as a wide range of other areas such as point-of-care monitoring of treatment and disease progression, environmental monitoring, food control, drug discovery, forensics and biomedical research. A wide range of techniques can be used for the development of biosensors. Their coupling with high-affinity biomolecules allows the sensitive and selective detection of a range of analytes. We give a general introduction to biosensors and biosensing technologies, including a brief historical overview, introducing key developments in the field and illustrating the breadth of biomolecular sensing strategies and the expansion of nanotechnological approaches that are now available. PMID:27365030

Role of pirfenidone in the management of pulmonary fibrosis.

PubMed

Meyer, Keith C; Decker, Catherine A

2017-01-01

Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antifibrotic agents have demonstrated lessening of lung function decline over time. Pirfenidone has been shown to significantly slow decline in forced vital capacity (FVC) over time and prolong progression-free survival, which led to its licensing by the United States Food and Drug Administration (FDA) in 2014 for the treatment of patients with IPF. However, pirfenidone has been associated with significant side effects, and patients treated with pirfenidone must be carefully monitored. We review recent and ongoing clinical research and experience with pirfenidone as a pharmacologic therapy for patients with IPF, provide a suggested approach to incorporate pirfenidone into a treatment algorithm for patients with IPF, and examine the potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by progressive pulmonary fibrosis.

A Curricular-Sampling Approach to Progress Monitoring: Mathematics Concepts and Applications

ERIC Educational Resources Information Center

Fuchs, Lynn S.; Fuchs, Douglas; Zumeta, Rebecca O.

2008-01-01

Progress monitoring is an important component of effective instructional practice. Curriculum-based measurement (CBM) is a form of progress monitoring that has been the focus of rigorous research. Two approaches for formulating CBM systems exist. The first is to assess performance regularly on a task that serves as a global indicator of competence…

Students, Teachers, and Schools as Sources of Variability, Integrity, and Sustainability in Implementing Progress Monitoring

ERIC Educational Resources Information Center

Bolt, Daniel M.; Ysseldyke, Jim; Patterson, Michael J.

2010-01-01

A three-level variance decomposition analysis was used to examine the sources of variability in implementation of a technology-enhanced progress monitoring system within each year of a 2-year study using a randomized-controlled design. We show that results of technology-enhanced progress monitoring are not necessarily a measure of student…

Hypothyroidism in the elderly: diagnosis and management

PubMed Central

Bensenor, Isabela M; Olmos, Rodrigo D; Lotufo, Paulo A

2012-01-01

Thyroid disorders are highly prevalent, occurring most frequently in aging women. Thyroid-associated symptoms are very similar to symptoms of the aging process; thus, improved methods for diagnosing overt and subclinical hypothyroidism in elderly people are crucial. Thyrotropin measurement is considered to be the main test for detecting hypothyroidism. Combined evaluations of thyroid stimulating hormone (TSH) and free-thyroxine can detect overt hypothyroidism (high TSH with low free-thyroxine levels) and subclinical hypothyroidism (high TSH with normal free-thyroxine levels). It is difficult to confirm the diagnosis of thyroid diseases based only on symptoms, but presence of symptoms could be an indicator of who should be evaluated for thyroid function. The most important reasons to treat overt hypothyroidism are to relieve symptoms and avoid progression to myxedema. Overt hypothyroidism is classically treated using L-thyroxine; elderly patients require a low initial dose that is increased every 4 to 6 weeks until normalization of TSH levels. After stabilization, TSH levels are monitored yearly. There is no doubt about the indication for treatment of overt hypothyroidism, but indications for treatment of subclinical disease are controversial. Although treatment of subclinical hypothyroidism may result in lipid profile improvement, there is no evidence that this improvement is associated with decreased cardiovascular or all-cause mortality in elderly patients. In patients with a high risk of progression from subclinical to overt disease, close monitoring of thyroid function could be the best option. PMID:22573936

Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

PubMed

Su, Jen-Min; Huang, Yu-Fang; Chen, Helen H W; Cheng, Ya-Min; Chou, Cheng-Yang

2006-05-01

To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

The vertical monitor position for presbyopic computer users with progressive lenses: how to reach clear vision and comfortable head posture.

PubMed

Weidling, Patrick; Jaschinski, Wolfgang

2015-01-01

When presbyopic employees are wearing general-purpose progressive lenses, they have clear vision only with a lower gaze inclination to the computer monitor, given the head assumes a comfortable inclination. Therefore, in the present intervention field study the monitor position was lowered, also with the aim to reduce musculoskeletal symptoms. A comparison group comprised users of lenses that do not restrict the field of clear vision. The lower monitor positions led the participants to lower their head inclination, which was linearly associated with a significant reduction in musculoskeletal symptoms. However, for progressive lenses a lower head inclination means a lower zone of clear vision, so that clear vision of the complete monitor was not achieved, rather the monitor should have been placed even lower. The procedures of this study may be useful for optimising the individual monitor position depending on the comfortable head and gaze inclination and the vertical zone of clear vision of progressive lenses. For users of general-purpose progressive lenses, it is suggested that low monitor positions allow for clear vision at the monitor and for a physiologically favourable head inclination. Employees may improve their workplace using a flyer providing ergonomic-optometric information.

Monitoring HIV and AIDS Related Policy Reforms: A Road Map to Strengthen Policy Monitoring and Implementation in PEPFAR Partner Countries

PubMed Central

2016-01-01

Achieving an AIDS-free generation will require the adoption and implementation of critical health policy reforms. However, countries with high HIV burden often have low policy development, advocacy, and monitoring capacity. This lack of capacity may be a significant barrier to achieving the AIDS-free generation goals. This manuscript describes the increased focus on policy development and implementation by the United States President’s Emergency Plan for AIDS Relief (PEPFAR). It evaluates the curriculum and learning modalities used for two regional policy capacity building workshops organized around the PEPFAR Partnership Framework agreements and the Road Map for Monitoring and Implementing Policy Reforms. A total of 64 participants representing the U.S. Government, partner country governments, and civil society organizations attended the workshops. On average, participants responded that their policy monitoring skills improved and that they felt they were better prepared to monitor policy reforms three months after the workshop. When followed-up regarding utilization of the Road Map action plan, responses were mixed. Reasons cited for not making progress included an inability to meet or a lack of time, personnel, or governmental support. This lack of progress may point to a need for building policy monitoring systems in high HIV burden countries. Because the success of policy reforms cannot be measured by the mere adoption of written policy documents, monitoring the implementation of policy reforms and evaluating their public health impact is essential. In many high HIV burden countries, policy development and monitoring capacity remains weak. This lack of capacity could hinder efforts to achieve the ambitious AIDS-free generation treatment, care and prevention goals. The Road Map appears to be a useful tool for strengthening these critical capacities. PMID:26914708

CEA monitoring of palliative treatment for colorectal carcinoma.

PubMed Central

Herrera, M A; Chu, T M; Holyoke, E D; Mittelman, A

1977-01-01

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable. PMID:64132

What Is Scientifically-Based Research on Progress Monitoring?

ERIC Educational Resources Information Center

Fuchs, Lynn S.; Fuchs, Douglas

2001-01-01

When teachers use systematic progress monitoring to track their students progress in reading, mathematics, or spelling, they are better able to identify students in need of additional or different forms of instruction, they design stronger instructional programs, and their students achieve better. This document first describes progress monitoring…

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

PubMed Central

Kristinsson, Sigurdur Y.

2011-01-01

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed. PMID:21441462

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

PubMed

Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

2011-05-26

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

Monitoring clinical progression with mitochondrial disease biomarkers

PubMed Central

Steele, Hannah E; Horvath, Rita; Lyon, Jon J; Chinnery, Patrick F

2017-01-01

Abstract Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies. PMID:28969370

Longitudinal whole genome analysis of pre and post drug treatment Mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.

PubMed

Datta, Gargi; Nieto, Luisa M; Davidson, Rebecca M; Mehaffy, Carolina; Pederson, Caroline; Dobos, Karen M; Strong, Michael

2016-05-01

Tuberculosis (TB) is one of the leading causes of death due to an infectious disease in the world. Understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant TB cases. We have analyzed three pairs of Mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. In the rifampicin resistant strain, we confirmed a mutation in rpoB (S450L) that is known to confer resistance to rifampicin. We discovered a novel L101R mutation in the katG gene of an isoniazid resistant strain, which may directly contribute to isoniazid resistance due to the proximity of the mutation to the katG isoniazid-activating site. Another isoniazid resistant strain had a rare mutation in the start codon of katG. We also identified a number of mutations in each longitudinal pair, such as toxin-antitoxin mutations that may influence the progression towards resistance or may play a role in compensatory fitness. These findings improve our knowledge of drug resistance progression during therapy and provide a methodology to monitor longitudinal strains using whole genome sequencing, polymorphism comparison, and functional annotation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Physiology and Electrical Activity of Uterine Contractions

PubMed Central

Garfield, Robert E.; Maner, William L.

2007-01-01

Presently, there is no effective treatment for preterm labor. The most obvious reason for this anomaly is that there is no objective manner to evaluate the progression of pregnancy through steps leading to labor, either at term or preterm. Several techniques have been adopted to monitor labor, and/or to diagnose labor, but they are either subjective or indirect, and they do not provide an accurate prediction of when labor will occur. With no method to determine preterm labor, treatment might never improve. Uterine EMG (electromyography) methods may provide such needed diagnostics. PMID:17659954

Presenters in Focus: Updating Your Toolkit for Monitoring Progress of Younger Struggling Readers--Q&A with Nathan Clemens

ERIC Educational Resources Information Center

Clemens, Nathan

2017-01-01

Using a data-driven approach to effectively monitor progress remains an important staple for school psychologists. However, progress monitoring approaches vary significantly based on the age and development of the student, requiring a nuanced and unique approach, particularly for young emerging readers. In this Presenters in Focus Q&A,…

Progress Monitoring with Computer Adaptive Assessments: The Impact of Data Collection Schedule on Growth Estimates

ERIC Educational Resources Information Center

Nelson, Peter M.; Van Norman, Ethan R.; Klingbeil, Dave A.; Parker, David C.

2017-01-01

Although extensive research exists on the use of curriculum-based measures for progress monitoring, little is known about using computer adaptive tests (CATs) for progress-monitoring purposes. The purpose of this study was to evaluate the impact of the frequency of data collection on individual and group growth estimates using a CAT. Data were…

Evaluating the Responsiveness to Therapeutic Change with Routine Outcome Monitoring: A Comparison of the Symptom Questionnaire-48 (SQ-48) with the Brief Symptom Inventory (BSI) and the Outcome Questionnaire-45 (OQ-45).

PubMed

Carlier, Ingrid V E; Kovács, Viktória; van Noorden, Martijn S; van der Feltz-Cornelis, Christina; Mooij, Nanda; Schulte-van Maaren, Yvonne W M; van Hemert, Albert M; Zitman, Frans G; Giltay, Erik J

2017-01-01

Assessment of psychological distress is important, because it may help to monitor treatment effects and predict treatment outcomes. We previously developed the 48-item Symptom Questionnaire (SQ-48) as a public domain self-report psychological distress instrument and showed good internal consistency as well as good convergent and divergent validity among clinical and non-clinical samples. The present study, conducted among psychiatric outpatients in a routine clinical setting, describes additional psychometric properties of the SQ-48. The primary focus is on responsiveness to therapeutic change, which to date has been rarely examined within psychiatry or clinical psychology. Since a questionnaire should also be stable when no clinically important change occurs, we also examined test-retest reliability within a test-retest design before treatment (n = 43). A pre-treatment/post-treatment design was used for responsiveness to therapeutic change, comparing the SQ-48 with two internationally widely used instruments: the Brief Symptom Inventory (n = 97) and the Outcome Questionnaire-45 (n = 109). The results showed that the SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change, without significant differences between the questionnaires in terms of responsiveness. In sum, the SQ-48 is a psychometrically sound public domain self-report instrument that can be used for routine outcome monitoring, as a benchmark tool or for research purposes. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message The SQ-48 is developed as a public domain self-report questionnaire, in line with growing efforts to develop clinical instruments that are free of charge. The SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change or patient progress. There were no significant differences in terms of responsiveness between the SQ-48 and BSI or OQ-45. The SQ-48 can be used as a routine evaluation outcome measure for quality assurance in clinical practice. Providing feedback on patient progress via outcome measures could contribute to the enhancement of treatment outcomes. Copyright © 2015 John Wiley & Sons, Ltd.

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their molecular target and emit a detectable signal.

Diagnosis and Management of Hepatitis C Virus Infection.

PubMed

Mukherjee, Ronita; Burns, Andrew; Rodden, Diane; Chang, Frances; Chaum, Manita; Garcia, Nancy; Bollipalli, Nikitha; Niemz, Angelika

2015-10-01

The hepatitis C virus (HCV) infects more than 200 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to chronic liver disease, creating a heavy economic burden on resource-poor countries and lowering patient quality of life. Effective HCV diagnosis, treatment selection, and treatment monitoring are important in stopping disease progression. Serological assays, which detect anti-HCV antibodies in the patient after seroconversion, are used for initial HCV diagnosis. Qualitative and quantitative molecular assays are used to confirm initial diagnosis, determine viral load, and genotype the dominant strain. Viral load and genotype information are used to guide appropriate treatment. Various other biomarker assays are performed to assess liver function and enable disease staging. Most of these diagnostic methods are mature and routinely used in high-resource countries with well-developed laboratory infrastructure. Few technologies, however, are available that address the needs of low-resource areas with high HCV prevalence, such as Africa and Southeast Asia. © 2015 Society for Laboratory Automation and Screening.

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

PubMed

Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-09-01

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system

PubMed Central

Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-01-01

Diabetic nephropathy (DN) affects an estimated 20%–40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. PMID:25116004

Progress Monitoring the Effects of Daily Report Cards across Elementary and Secondary Settings Using Direct Behavior Rating: Single Item Scales

ERIC Educational Resources Information Center

Miller, Faith G.; Crovello, Nicholas J.; Chafouleas, Sandra M.

2017-01-01

Direct Behavior Rating-Single Item Scales (DBR-SIS) have been advanced as a promising, systematic, behavioral, progress-monitoring method that is flexible, efficient, and defensible. This study aimed to extend existing literature on the use of DBR-SIS in elementary and secondary settings, and to examine methods of monitoring student progress in…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Kindergarten. Technical Report # 0921

ERIC Educational Resources Information Center

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in kindergarten. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from…

Monitoring Progress in Child Poverty Reduction: Methodological Insights and Illustration to the Case Study of Bangladesh

ERIC Educational Resources Information Center

Roche, Jose Manuel

2013-01-01

Important steps have been taken at international summits to set up goals and targets to improve the wellbeing of children worldwide. Now the world also has more and better data to monitor progress. This paper presents a new approach to monitoring progress in child poverty reduction based on the Alkire and Foster adjusted headcount ratio and an…

Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Diabetes.

PubMed

Rao, Pasupuleti Visweswara; Gan, Siew Hua

2015-01-01

Nanotechnology is a field encompassing nanostructures, nanomaterials and nanoparticles, which are of increasing importance to researchers and industrial players alike. Nanotechnology addresses the construction and consumption of substances and devices on the nanometer scale. Nanomedicine is a new field that combines nanotechnology with medicine to boost human health care. Nanomedicine is an interdisciplinary field that includes various areas of biology, chemistry, physics and engineering. The most important problems related to diabetes management, such as self-monitoring of blood glucose levels and insulin injections, can now be conquered due to progress in nanomedicine, which offers glucose nanosensors, the layer-by-layer technique, carbon nanotubes, quantum dots, oral insulins, microspheres, artificial pancreases and nanopumps. In this review, the key methodological and scientific characteristics of nanomedicine related to diabetes treatment, glucose monitoring and insulin administration are discussed.

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Laser-induced autofluorescence-based objective evaluation of burn tissue repair in mice.

PubMed

Rathnakar, Bharath; Rao, Bola Sadashiva Satish; Prabhu, Vijendra; Chandra, Subhash; Mahato, Krishna Kishore

2018-05-01

Management of burn injuries are a growing concern, especially in determining the progression of healing. Several techniques are being practiced in clinics and have been considered all-time standard approaches to determine pre- and post-treatment outcomes of a healthy healing. However, these kinds of methods involve repeated biopsies and thereby hindering tissue repair. In view of this, our perspective was to develop a non-invasive tool in an attempt to provide a solution to determine the progression of healing, in vivo. Hence, the present study was designed to investigate the ability of laser-induced fluorescence (LIF) to monitor the variations in collagen intensity at various time points (0, 2, 6, 12, 18, 24, and 30 days) during burn tissue repair in mice, post low-power laser therapy (LPLT). The spectral findings demonstrated a significant change in collagen intensity as observed on day 24 (p < 0.05) and 30 (p < 0.01), when treated with LPLT (830 nm 3 J/cm 2 ) as compared to untreated control. From the observation, it was evident that the LIF could objectively monitor the progression of burn tissue repair in vivo.

Magnetic field effects on spectrally resolved lifetime of on-line oxygen monitoring using magneto-optic probes

NASA Astrophysics Data System (ADS)

Mermut, O.; Gallant, P.; Le Bouch, N.; Leclair, S.; Noiseux, I.; Vernon, M.; Morin, J.-F.; Diamond, K.; Patterson, M. S.; Samkoe, K.; Pogue, B.

2009-02-01

Multimodal agents that serve as both probes for contrast and light-activated effectors of cellular processes in diseased tissue were developed. These agents were introduced into multicellular tumor spheroids (3D tissue models) and in the chorioallantoic membrane (CAM) of a chicken embryo. The luminescence decay was examined using a novel technique involving a spectrally-resolved fluorescence lifetime apparatus integrated with a weak electromagnet. A spectrallyresolved lifetime setup was used to identify magneto-optic species sensitive to magnetic field effects and distinguish from background emissions. We demonstrate that the applied magnetic fields can alter reaction rates and product distribution of some dyes detected by time- and spectrally-resolved luminescence changes. We will discuss the use of exogenous magneto-optical probes taken up in tumors to both induce phototoxicity, a process that is governed by complex and dynamically evolving mechanisms involving reactive oxygen species, and monitor treatment progress. The magnetic field enhancement, measured over a range of weak fields (0-300 mT) is correlated to oxygenation and may be used to monitor dynamic changes occurring due to oxygen consumption over the course of photodynamic therapy. Such online measurements provide the possibility to derive real-time information about response to treatment via monitoring magnetic field enhancement/suppression of the time-resolved, spectrally-resolved luminescence of the probe at the site of the treatment directly. Magnetic perturbation of lifetime can serve as a status reporter, providing optical feedback of oxygen-mediated treatments in situ and allowing for real-time adjustment of a phototherapy treatment plan.

Program Monitoring Practices for Teachers of the Deaf and Hard of Hearing in Early Intervention

ERIC Educational Resources Information Center

Thomas, Anne E.; Marvin, Christine A.

2016-01-01

Program monitoring is an important and necessary assessment practice within the field of early childhood deaf education. Effective program monitoring requires a focus on both the consistent implementation of intervention strategies (fidelity) and the assessment of children's ongoing progress in response to interventions (progress monitoring).…

Ultrasound monitoring of the treatment of clinically significant knee osteoarthritis.

PubMed

Vojtassak, J; Vojtassak, J

2014-01-01

The study presented an ultrasound (US) monitoring of treatment as a new imaging US method with the results of therapy of clinically significant knee osteoarthritis. X-ray is widely used for knee osteoarthritis classification, which does not involve the evaluation of the soft tissue. High frequency and high resolution US of joints (arthrosonography, echoarthrography) assess not only morphologic but also functional changes in the knee joint. In the prospective study, 110 patients with clinically significant knee osteoarthritis were treated non-operative. US examination and US monitoring of therapy was performed during 24 weeks therapy period. A remission of pathomorphologic (marginal osteofytes) and pathophysiologic (effusion in anterior knee and Baker´s cyst) attributes were evaluated according the US classification. Pathomorphologic attributes changes showed a static state, without remission or progression. Pathophysiologic attributes changes showed a remission during the study period. The highest remission was in the first three weeks, 60 % anterior knee effusion and 62 % Baker´s cyst. At the end of study, no changes from the initial US grade was observed in 16 % of effusion in anterior knee and 22 % of Baker´s cyst. Therapeutic resistant Baker´s cyst was present at the end of study in 36 %. We demonstrated a new method - US monitoring of therapy, which can objectivize the efficiency of treatment of clinically significant knee osteoarthritis. We would recommend US monitoring of therapy for the routine use in orthopedic clinical praxis (Tab. 6, Graph 3, Fig. 3, Ref. 15).

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 1. Technical Report # 0919

ERIC Educational Resources Information Center

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grade 1. These measures, available as part of easyCBM [TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from schools…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 3. Technical Report # 09-02

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 2. Technical Report # 0920

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 5. Technical Report # 09-01

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 4. Technical Report # 09-03

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 7. Technical Report 0908

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 8. Technical Report # 09-04

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

An Examination of an Early Intervention Reading Program Focusing on the Progress Monitoring of Literacy Skills and the Reading Self-Concepts of Struggling Readers

ERIC Educational Resources Information Center

Samuelson, Teresa C.

2010-01-01

The purpose of this study was to examine progress monitoring, reading self-concept, and the literacy skills of first and second grade struggling readers. Progress monitoring is an instructional process used by teachers to assess students' academic performance on a regular basis, typically weekly or monthly. When based on the skill level of the…

Mutation testing for directing upfront targeted therapy and post-progression combination therapy strategies in lung adenocarcinoma

PubMed Central

Salgia, Ravi

2016-01-01

ABSTRACT Introduction: Advances in the biology of non-small-cell lung cancer, especially adenocarcinoma, reveal multiple molecular subtypes driving oncogenesis. Accordingly, individualized targeted therapeutics are based on mutational diagnostics. Areas covered: Advances in strategies and techniques for individualized treatment, particularly of adenocarcinoma, are described through literature review. Approved therapies are established for some molecular subsets, with new driver mutations emerging that represent increasing proportions of patients. Actionable mutations are de novo oncogenic drivers or acquired resistance mediators, and mutational profiling is important for directing therapy. Patients should be monitored for emerging actionable resistance mutations. Liquid biopsy and associated multiplex diagnostics will be important means to monitor patients during treatment. Expert commentary: Outcomes with targeted agents may be improved by integrating mutation screens during treatment to optimize subsequent therapy. In order for this to be translated into impactful patient benefit, appropriate platforms and strategies need to be optimized and then implemented universally. PMID:27139190

HIFU Monitoring and Control with Dual-Mode Ultrasound Arrays

NASA Astrophysics Data System (ADS)

Casper, Andrew Jacob

The biological effects of high-intensity focused ultrasound (HIFU) have been known and studied for decades. HIFU has been shown capable of treating a wide variety of diseases and disorders. However, despite its demonstrated potential, HIFU has been slow to gain clinical acceptance. This is due, in part, to the difficulty associated with robustly monitoring and controlling the delivery of the HIFU energy. The non-invasive nature of the surgery makes the assessment of treatment progression difficult, leading to long treatment times and a significant risk of under treatment. This thesis research develops new techniques and systems for robustly monitoring HIFU therapies for the safe and efficacious delivery of the intended treatment. Systems and algorithms were developed for the two most common modes of HIFU delivery systems: single-element and phased array applicators. Delivering HIFU with a single element transducer is a widely used technique in HIFU therapies. The simplicity of a single element offers many benefits in terms of cost and overall system complexity. Typical monitoring schemes rely on an external device (e.g. diagnostic ultrasound or MRI) to assess the progression of therapy. The research presented in this thesis explores using the same element to both deliver and monitor the HIFU therapy. The use of a dual-mode ultrasound transducer (DMUT) required the development of an FPGA based single-channel arbitrary waveform generator and high-speed data acquisition unit. Data collected from initial uncontrolled ablations led to the development of monitoring and control algorithms which were implemented directly on the FPGA. Close integration between the data acquisition and arbitrary waveform units allowed for fast, low latency control over the ablation process. Results are presented that demonstrate control of HIFU therapies over a broad range of intensities and in multiple in vitro tissues. The second area of investigation expands the DMUT research to an ultrasound phased-array. The phased-array allows for electronic steering of the HIFU focus and imaging of the acoustic medium. Investigating the dual-mode ultrasound array (DMUA) required the design and construction of a novel ultrasound-guided focused ultrasound (USgFUS) platform. The platform consisted of custom hardware designed for the unique requirements of operating a phased-array in both therapeutic and imaging modes. The platform also required the development of FPGA based signal processing and GPU based beamforming algorithms for online monitoring of the therapy process. The results presented in this thesis represent the first demonstration of a real-time USgFUS platform based around a DMUA. Experimental imaging and therapy results from series of animal experiments, including a 12 animal GLP study, are presented. In addition, in vitro control results, which build upon the DMUT work, are presented.

Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

PubMed

Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

2007-03-01

Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

[Efficacy of lisdexamphetamine to improve the behavioural and cognitive symptoms of attention deficit hyperactivity disorder: treatment monitored by means of the AULA Nesplora virtual reality test].

PubMed

Diaz-Orueta, U; Fernandez-Fernandez, M A; Morillo-Rojas, M D; Climent, G

2016-07-01

Lisdexanfetamine (LDX) is the drug for attention deficit hyperactivity disorder (ADHD) undergoing the largest research volume in the latest years. However, no studies certify its usefulness for the improvement of cognitive functioning in ADHD. To evaluate the efficacy of LDX in the behavioral and cognitive improvement of a group of patients with ADHD. Such efficacy was measured by means of the administration of AULA Nesplora virtual reality test before the prescription of pharmacological treatment and right after the treatment with LDX. The sample comprised 85 patients between 6 and 16 years, with clinical diagnosis of ADHD, who attended treatment in a neuropediatrics consultation. All patients started pharmacological treatment with the proper dose of LDX after the clinical interview and the first administration of AULA test. After an average treatment of 7.5 months, AULA was administered again and the treatment progress based on cognitive and motor symptomatology was assessed. Results showed highly significant improvements in selective and sustained attention, quality of attention focus and hyperactivity; moderate improvements in impulsivity; and an incidence close to zero in processing speed. LDX constitutes an adequate treatment for the substantial improvement of attention and hyperactivity; such improvement can be monitored accurately by means of AULA virtual reality test.

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

PubMed

Usmani, S Z; Cavenagh, J D; Belch, A R; Hulin, C; Basu, S; White, D; Nooka, A; Ervin-Haynes, A; Yiu, W; Nagarwala, Y; Berger, A; Pelligra, C G; Guo, S; Binder, G; Gibson, C J; Facon, T

2016-01-01

To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

Measuring Coverage in MNCH: Challenges in Monitoring the Proportion of Young Children with Pneumonia Who Receive Antibiotic Treatment

PubMed Central

Campbell, Harry; el Arifeen, Shams; Hazir, Tabish; O'Kelly, James; Bryce, Jennifer; Rudan, Igor; Qazi, Shamim Ahmad

2013-01-01

Pneumonia remains a major cause of child death globally, and improving antibiotic treatment rates is a key control strategy. Progress in improving the global coverage of antibiotic treatment is monitored through large household surveys such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), which estimate antibiotic treatment rates of pneumonia based on two-week recall of pneumonia by caregivers. However, these survey tools identify children with reported symptoms of pneumonia, and because the prevalence of pneumonia over a two-week period in community settings is low, the majority of these children do not have true pneumonia and so do not provide an accurate denominator of pneumonia cases for monitoring antibiotic treatment rates. In this review, we show that the performance of survey tools could be improved by increasing the survey recall period or by improving either overall discriminative power or specificity. However, even at a test specificity of 95% (and a test sensitivity of 80%), the proportion of children with reported symptoms of pneumonia who truly have pneumonia is only 22% (the positive predictive value of the survey tool). Thus, although DHS and MICS survey data on rates of care seeking for children with reported symptoms of pneumonia and other childhood illnesses remain valid and important, DHS and MICS data are not able to give valid estimates of antibiotic treatment rates in children with pneumonia. PMID:23667338

Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging.

PubMed

Wu, Shulian; Huang, Yudian; Tang, Qinggong; Li, Zhifang; Horng, Hannah; Li, Jiatian; Wu, Zaihua; Chen, Yu; Li, Hui

2018-03-01

Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.

Pediatric morphea (localized scleroderma): review of 136 patients.

PubMed

Christen-Zaech, Stéphanie; Hakim, Miriam D; Afsar, F Sule; Paller, Amy S

2008-09-01

Morphea is an autoimmune inflammatory sclerosing disorder that may cause permanent functional disability and disfigurement. We sought to determine the clinical features of morphea in a large pediatric cohort. We conducted a retrospective chart review of 136 pediatric patients with morphea from one center, 1989 to 2006. Most children showed linear morphea, with a disproportionately high number of Caucasian and female patients. Two patients with rapidly progressing generalized or extensive linear morphea and arthralgias developed restrictive pulmonary disease. Initial oral corticosteroid treatment and long-term methotrexate administration stabilized and/or led to disease improvement in most patients with aggressive disease. Retrospective analysis, relatively small sample size, and risk of a selected referral population to the single site are limitations. These data suggest an increased prevalence of morphea in Caucasian girls, and support methotrexate as treatment for problematic forms. Visceral manifestations rarely occur; the presence of progressive problematic cutaneous disease and arthralgias should trigger closer patient monitoring.

ELF (Extremely Low Frequency) Communications System Ecological Monitoring Program: Summary of 1987 Progress

DTIC Science & Technology

1989-04-01

Development . Prenatal developmental stages are especially sensitive to environmental perturbations. At present, there is conflicting evidence of direct EM...effects on embryonic or fetal development . In addition, possible effects of the ELF system on parental behavior could also have an indirect effect on... development . The purpose of this element is to determine the incidence of abnormalities in embryonic development in tree swallows at treatment and control

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

PubMed

Zeestraten, Eva Anna; Benjamin, Philip; Lambert, Christian; Lawrence, Andrew John; Williams, Owen Alan; Morris, Robin Guy; Barrick, Thomas Richard; Markus, Hugh Stephen

2016-01-01

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD.

Assessment of the role of circulating breast cancer cells in tumor formation and metastatic potential using in vivo flow cytometry

NASA Astrophysics Data System (ADS)

Hwu, Derrick; Boutrus, Steven; Greiner, Cherry; Dimeo, Theresa; Kuperwasser, Charlotte; Georgakoudi, Irene

2011-04-01

The identification of breast cancer patients who will ultimately progress to metastatic disease is of significant clinical importance. The quantification and assessment of circulating tumor cells (CTCs) has been proposed as one strategy to monitor treatment effectiveness and disease prognosis. However, CTCs have been an elusive population of cells to study because of their small number and difficulties associated with isolation protocols. In vivo flow cytometry (IVFC) can overcome these limitations and provide insights in the role these cells play during primary and metastatic tumor growth. In this study, we used two-color IVFC to examine, for up to ten weeks following orthotopic implantation, changes in the number of circulating human breast cells expressing GFP and a population of circulating hematopoietic cells with strong autofluorescence. We found that the number of detected CTCs in combination with the number of red autofluorescent cells (650 to 690 nm) during the first seven days following implantation was predictive in development of tumor formation and metastasis eight weeks later. These results suggest that the combined detection of these two cell populations could offer a novel approach in the monitoring and prognosis of breast cancer progression, which in turn could aid significantly in their effective treatment.

Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia

PubMed Central

Stoessl, A. Jon; Lehericy, Stephane; Strafella, Antonio P.

2015-01-01

Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson’s disease from healthy controls, and show great promise for differentiation between Parkinson’s disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson’s disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson’s disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression. PMID:24954673

Prescription-event monitoring: methodology and recent progress.

PubMed

Rawson, N S; Pearce, G L; Inman, W H

1990-01-01

Event monitoring was first suggested 25 years ago as a way of detecting adverse reactions to drugs. Prescription-event monitoring (PEM), which has been developed by the Drug Safety Research Unit, is the first large-scale systematic post-marketing surveillance method to use event monitoring in the U.K. PEM identifies patients, who have been prescribed a particular drug, and their doctors from photocopies of National Health Service prescriptions which are processed centrally in England. A personalized follow-up questionnaire ("green form") is mailed to each patient's general practitioner, usually on the first anniversary of the initial prescription, asking for information about the patient, especially any "events" that he or she may have experienced since beginning treatment with the drug. The methodology of PEM is presented, together with examples of analyses that can be performed using results from recent studies. The problems and benefits of PEM are discussed.

Data Collection and Analysis Using Wearable Sensors for Monitoring Knee Range of Motion after Total Knee Arthroplasty

PubMed Central

Chiang, Chih-Yen; Chen, Kun-Hui; Liu, Kai-Chun; Hsu, Steen Jun-Ping; Chan, Chia-Tai

2017-01-01

Total knee arthroplasty (TKA) is the most common treatment for degenerative osteoarthritis of that articulation. However, either in rehabilitation clinics or in hospital wards, the knee range of motion (ROM) can currently only be assessed using a goniometer. In order to provide continuous and objective measurements of knee ROM, we propose the use of wearable inertial sensors to record the knee ROM during the recovery progress. Digitalized and objective data can assist the surgeons to control the recovery status and flexibly adjust rehabilitation programs during the early acute inpatient stage. The more knee flexion ROM regained during the early inpatient period, the better the long-term knee recovery will be and the sooner early discharge can be achieved. The results of this work show that the proposed wearable sensor approach can provide an alternative for continuous monitoring and objective assessment of knee ROM recovery progress for TKA patients compared to the traditional goniometer measurements. PMID:28241434

Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

NASA Astrophysics Data System (ADS)

Stolz, Martin; Gottardi, Riccardo; Raiteri, Roberto; Miot, Sylvie; Martin, Ivan; Imer, Raphaël; Staufer, Urs; Raducanu, Aurelia; Düggelin, Marcel; Baschong, Werner; Daniels, A. U.; Friederich, Niklaus F.; Aszodi, Attila; Aebi, Ueli

2009-03-01

The pathological changes in osteoarthritis-a degenerative joint disease prevalent among older people-start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. Methods A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. Discussion This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. Trial registration This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008). PMID:24997587

Wearable sensors for human health monitoring

NASA Astrophysics Data System (ADS)

Asada, H. Harry; Reisner, Andrew

2006-03-01

Wearable sensors for continuous monitoring of vital signs for extended periods of weeks or months are expected to revolutionize healthcare services in the home and workplace as well as in hospitals and nursing homes. This invited paper describes recent research progress in wearable health monitoring technology and its clinical applications, with emphasis on blood pressure and circulatory monitoring. First, a finger ring-type wearable blood pressure sensor based on photo plethysmogram is presented. Technical issues, including motion artifact reduction, power saving, and wearability enhancement, will be addressed. Second, sensor fusion and sensor networking for integrating multiple sensors with diverse modalities will be discussed for comprehensive monitoring and diagnosis of health status. Unlike traditional snap-shot measurements, continuous monitoring with wearable sensors opens up the possibility to treat the physiological system as a dynamical process. This allows us to apply powerful system dynamics and control methodologies, such as adaptive filtering, single- and multi-channel system identification, active noise cancellation, and adaptive control, to the monitoring and treatment of highly complex physiological systems. A few clinical trials illustrate the potentials of the wearable sensor technology for future heath care services.

The effect of carprofen on selected markers of bone metabolism in dogs with chronic osteoarthritis.

PubMed

Liesegang, A; Limacher, S; Sobek, A

2007-08-01

The purpose of this study was to investigate the effect of the nonsteroidal anti-inflammatory drug carprofen on bone turnover and to monitor the progress of chronic osteoarthritic dogs by measuring different bone markers and radiographic evalutation of the corresponding joints. For this purpose 20 dogs of different ages and weight were devided into 2 groups. Ten dogs were assigned to Group R, treated with carprofen, and ten dogs to Group C, which had no treatment. Radiographs of the affected joints were reviewed initially and six months later at the end of the experiment. Blood was taken 8 times from each dog. Four bone markers (Osteocalcin (OC), bone-specific alkaline phosphatase (bAP), carboxyterminal telopeptide of type I collagen (ICTP), serum CrossLaps (CTX) as well as 1,25-(OH)2-Vitamin D and parathyroid hormone (PTH) were monitored for 6 months. No significant group effects on bone markers were notied. In Group R a decrease in ICTP concentrations during the first three months and a significant decrease in CTX concentrations in the first two months of the study were observed. The bone formation marker bAP revealed a significant decrease throughout the experiment. Three dogs of Group C and one dog of Group R showed osteoarthritic progression in the radiographs. The significant decrease of CTX indicates that carprofentreatment could have a retarding effect on the progression of osteoarthritis. Radiological findings suggest that carprofen may delay osteophyte formation. The monitoring of focal metabolic processes as in bone of a osteoarthrotic joint is difficult, since the bone mass is very active and metabolic processes may have an influence on the monitoring.

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

PubMed Central

2014-01-01

Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

A Multidisciplinary Approach for Managing Severely Malaligned Lower Molars.

PubMed

Keinan, David; Birnboim-Blaum, Galit; Webber, Mariel

2016-01-01

An impacted mandibular molar is a common clinical situation that may damage adjacent teeth and impair periodontal health. Improper treatment brings the risk of damaging adjacent vital tissues. The risk can be reduced by early diagnosis and extraction of the impacted tooth by an experienced clinician. However, in clinical cases of two impacted molars, it may be beneficial for the patient to save at least one molar. This can be achieved by orthodontic alignment of one of the molars, while extracting the other. The decision should be based upon prognosis and risks for each procedure and for both teeth. The case presented here demonstrates a recommended clinical decision-making process before treatment, followed by monitored multidisciplinary treatment with adaptations made as the treatment progresses.

A Framework for Fibromyalgia Management for Primary Care Providers

PubMed Central

Arnold, Lesley M.; Clauw, Daniel J.; Dunegan, L. Jean; Turk, Dennis C.

2012-01-01

Fibromyalgia is a chronic widespread pain disorder commonly associated with comorbid symptoms, including fatigue and nonrestorative sleep. As in the management of other chronic medical disorders, the approach for fibromyalgia management follows core principles of comprehensive assessment, education, goal setting, multimodal treatment including pharmacological (eg, pregabalin, duloxetine, milnacipran) and nonpharmacological therapies (eg, physical activity, behavioral therapy, sleep hygiene, education), and regular education and monitoring of treatment response and progress. Based on these core management principles, this review presents a framework for primary care providers through which they can develop a patient-centered treatment program for patients with fibromyalgia. This proactive and systematic treatment approach encourages ongoing education and patient self-management and is designed for use in the primary care setting. PMID:22560527

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PubMed

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed Central

Ried, Karin; Eng, Peter; Sali, Avni

2017-01-01

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 out-of 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. PMID:28843267

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed

Ried, Karin; Eng, Peter; Sali, Avni

2017-08-27

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 outof 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. Creative Commons Attribution License

Advances in the Evaluation and Management of Esophageal Disease of Systemic Sclerosis

PubMed Central

Carlson, Dustin A.; Hinchcliff, Monique; Pandolfino, John E.

2015-01-01

Symptoms of heartburn and dysphagia, as well as objective findings of abnormal esophageal acid exposure and esophageal dysmotility are common in patients with systemic sclerosis (SSc). Treatments for SSc esophageal disease are generally limited to gastroesophageal reflux disease (GERD) treatment with proton pump inhibitors. Progresses made in esophageal diagnostic testing offer the potential for improved clinical characterization of esophageal disease in SSc that may help direct management decisions. In addition to reviewing GERD management in patients with SSc, present and potential uses of endoscopy, reflux monitoring, manometry, impedance planimetry, and endoscopic ultrasound are discussed. PMID:25475597

Female pattern hair loss: Current treatment concepts

PubMed Central

Dinh, Quan Q; Sinclair, Rodney

2007-01-01

Fewer than 45% of women go through life with a full head of hair. Female pattern hair loss is the commonest cause of hair loss in women and prevalence increases with advancing age. Affected women may experience psychological distress and impaired social functioning. In most cases the diagnosis can be made clinically and the condition treated medically. While many women using oral antiandrogens and topical minoxidil will regrow some hair, early diagnosis and initiation of treatment is desirable as these treatments are more effective at arresting progression of hair loss than stimulating regrowth. Adjunctive nonpharmacological treatment modalities such as counseling, cosmetic camouflage and hair transplantation are important measures for some patients. The histology of female pattern hair loss is identical to that of male androgenetic alopecia. While the clinical pattern of the hair loss differs between men, the response to oral antiandrogens suggests that female pattern hair loss is an androgen dependant condition, at least in the majority of cases. Female pattern hair loss is a chronic progressive condition. All treatments need to be continued to maintain the effect. An initial therapeutic response often takes 12 or even 24 months. Given this delay, monitoring for treatment effect through clinical photography or standardized clinical severity scales is helpful. PMID:18044135

MO-D-213-01: Workflow Monitoring for a High Volume Radiation Oncology Center

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

Laub, S; Dunn, M; Galbreath, G

2015-06-15

Purpose: Implement a center wide communication system that increases interdepartmental transparency and accountability while decreasing redundant work and treatment delays by actively monitoring treatment planning workflow. Methods: Intake Management System (IMS), a program developed by ProCure Treatment Centers Inc., is a multi-function database that stores treatment planning process information. It was devised to work with the oncology information system (Mosaiq) to streamline interdepartmental workflow.Each step in the treatment planning process is visually represented and timelines for completion of individual tasks are established within the software. The currently active step of each patient’s planning process is highlighted either red or greenmore » according to whether the initially allocated amount of time has passed for the given process. This information is displayed as a Treatment Planning Process Monitor (TPPM), which is shown on screens in the relevant departments throughout the center. This display also includes the individuals who are responsible for each task.IMS is driven by Mosaiq’s quality checklist (QCL) functionality. Each step in the workflow is initiated by a Mosaiq user sending the responsible party a QCL assignment. IMS is connected to Mosaiq and the sending or completing of a QCL updates the associated field in the TPPM to the appropriate status. Results: Approximately one patient a week is identified during the workflow process as needing to have his/her treatment start date modified or resources re-allocated to address the most urgent cases. Being able to identify a realistic timeline for planning each patient and having multiple departments communicate their limitations and time constraints allows for quality plans to be developed and implemented without overburdening any one department. Conclusion: Monitoring the progression of the treatment planning process has increased transparency between departments, which enables efficient communication. Having built-in timelines allows easy prioritization of tasks and resources and facilitates effective time management.« less

Wearable Technology for Chronic Wound Monitoring: Current Dressings, Advancements, and Future Prospects.

PubMed

Brown, Matthew S; Ashley, Brandon; Koh, Ahyeon

2018-01-01

Chronic non-healing wounds challenge tissue regeneration and impair infection regulation for patients afflicted with this condition. Next generation wound care technology capable of in situ physiological surveillance which can diagnose wound parameters, treat various chronic wound symptoms, and reduce infection at the wound noninvasively with the use of a closed loop therapeutic system would provide patients with an improved standard of care and an accelerated wound repair mechanism. The indicating biomarkers specific to chronic wounds include blood pressure, temperature, oxygen, pH, lactate, glucose, interleukin-6 (IL-6), and infection status. A wound monitoring device would help decrease prolonged hospitalization, multiple doctors' visits, and the expensive lab testing associated with the diagnosis and treatment of chronic wounds. A device capable of monitoring the wound status and stimulating the healing process is highly desirable. In this review, we discuss the impaired physiological states of chronic wounds and explain the current treatment methods. Specifically, we focus on improvements in materials, platforms, fabrication methods for wearable devices, and quantitative analysis of various biomarkers vital to wound healing progress.

Wearable Technology for Chronic Wound Monitoring: Current Dressings, Advancements, and Future Prospects

PubMed Central

Brown, Matthew S.; Ashley, Brandon; Koh, Ahyeon

2018-01-01

Chronic non-healing wounds challenge tissue regeneration and impair infection regulation for patients afflicted with this condition. Next generation wound care technology capable of in situ physiological surveillance which can diagnose wound parameters, treat various chronic wound symptoms, and reduce infection at the wound noninvasively with the use of a closed loop therapeutic system would provide patients with an improved standard of care and an accelerated wound repair mechanism. The indicating biomarkers specific to chronic wounds include blood pressure, temperature, oxygen, pH, lactate, glucose, interleukin-6 (IL-6), and infection status. A wound monitoring device would help decrease prolonged hospitalization, multiple doctors' visits, and the expensive lab testing associated with the diagnosis and treatment of chronic wounds. A device capable of monitoring the wound status and stimulating the healing process is highly desirable. In this review, we discuss the impaired physiological states of chronic wounds and explain the current treatment methods. Specifically, we focus on improvements in materials, platforms, fabrication methods for wearable devices, and quantitative analysis of various biomarkers vital to wound healing progress. PMID:29755977

Training General Education Pupils to Monitor Reading Using Curriculum-Based Measurement Procedures.

ERIC Educational Resources Information Center

Bentz, Johnell; And Others

1990-01-01

Although systematic monitoring of student progress has been associated with improved achievement, few teachers engage in progress monitoring because of testing-time requirements. Compared accuracy of 14 trained fourth- and fifth-grade general education students' curriculum-based reading assessments of second and third graders to accuracy of…

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

PubMed

Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

2015-11-10

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

PubMed Central

Cortazar, Ana Rosa; Liu, Xiaojing; Urosevic, Jelena; Castillo-Martin, Mireia; Fernández-Ruiz, Sonia; Morciano, Giampaolo; Caro-Maldonado, Alfredo; Guiu, Marc; Zúñiga-García, Patricia; Graupera, Mariona; Bellmunt, Anna; Pandya, Pahini; Lorente, Mar; Martín-Martín, Natalia; Sutherland, James David; Sanchez-Mosquera, Pilar; Bozal-Basterra, Laura; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Berenguer, Antonio; Embade, Nieves; Ugalde-Olano, Aitziber; Lacasa-Viscasillas, Isabel; Loizaga-Iriarte, Ana; Unda-Urzaiz, Miguel; Schultz, Nikolaus; Aransay, Ana Maria; Sanz-Moreno, Victoria; Barrio, Rosa; Velasco, Guillermo; Pinton, Paolo; Cordon-Cardo, Carlos; Carracedo, Arkaitz

2016-01-01

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator PGC1α suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is down-regulated in prostate cancer and associated to disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an Oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α-ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment. PMID:27214280

Feasibility of A-mode ultrasound attenuation as a monitoring method of local hyperthermia treatment.

PubMed

Manaf, Noraida Abd; Aziz, Maizatul Nadwa Che; Ridzuan, Dzulfadhli Saffuan; Mohamad Salim, Maheza Irna; Wahab, Asnida Abd; Lai, Khin Wee; Hum, Yan Chai

2016-06-01

Recently, there is an increasing interest in the use of local hyperthermia treatment for a variety of clinical applications. The desired therapeutic outcome in local hyperthermia treatment is achieved by raising the local temperature to surpass the tissue coagulation threshold, resulting in tissue necrosis. In oncology, local hyperthermia is used as an effective way to destroy cancerous tissues and is said to have the potential to replace conventional treatment regime like surgery, chemotherapy or radiotherapy. However, the inability to closely monitor temperature elevations from hyperthermia treatment in real time with high accuracy continues to limit its clinical applicability. Local hyperthermia treatment requires real-time monitoring system to observe the progression of the destroyed tissue during and after the treatment. Ultrasound is one of the modalities that have great potential for local hyperthermia monitoring, as it is non-ionizing, convenient and has relatively simple signal processing requirement compared to magnetic resonance imaging and computed tomography. In a two-dimensional ultrasound imaging system, changes in tissue microstructure during local hyperthermia treatment are observed in terms of pixel value analysis extracted from the ultrasound image itself. Although 2D ultrasound has shown to be the most widely used system for monitoring hyperthermia in ultrasound imaging family, 1D ultrasound on the other hand could offer a real-time monitoring and the method enables quantitative measurement to be conducted faster and with simpler measurement instrument. Therefore, this paper proposes a new local hyperthermia monitoring method that is based on one-dimensional ultrasound. Specifically, the study investigates the effect of ultrasound attenuation in normal and pathological breast tissue when the temperature in tissue is varied between 37 and 65 °C during local hyperthermia treatment. Besides that, the total protein content measurement was also conducted to investigate the relationship between attenuation and tissue denaturation level at different temperature ranges. The tissues were grouped according to their histology results, namely normal tissue with large predominance of cells (NPC), cancer tissue with large predominance of cells (CPC) and cancer with high collagen fiber content (CHF). The result shows that the attenuation coefficient of ultrasound measured following the local hyperthermia treatment increases with the increment of collagen fiber content in tissue as the CHF attenuated ultrasound at the highest rate, followed by NPC and CPC. Additionally, the attenuation increment is more pronounced at the temperature over 55 °C. This describes that the ultrasound wave experienced more energy loss when it propagates through a heated tissue as the tissue structure changes due to protein coagulation effect. Additionally, a significant increase in the sensitivity of attenuation to protein denaturation is also observed with the highest sensitivity obtained in monitoring NPC. Overall, it is concluded that one-dimensional ultrasound can be used as a monitoring method of local hyperthermia since its attenuation is very sensitive to the changes in tissue microstructure during hyperthermia.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

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

Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org; Choi, Junsung; Gonzalez, Ricardo J.

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significantmore » improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.« less

Multidrug-resistant tuberculosis around the world: what progress has been made?

PubMed Central

Mirzayev, Fuad; Wares, Fraser; Baena, Inés Garcia; Zignol, Matteo; Linh, Nguyen; Weyer, Karin; Jaramillo, Ernesto; Floyd, Katherine; Raviglione, Mario

2015-01-01

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB. PMID:25261327

Transient asymptomatic pulmonary opacities occurring during osimertinib treatment

PubMed Central

Noonan, Sinead A.; Sachs, Peter B.; Camidge, D. Ross

2017-01-01

Introduction Osimertinib is an Epidermal Growth Factor Receptor (EGFR) Inhibitor licensed for the treatment of EGFR mutant, T790M positive, non-small cell lung cancer (NSCLC). Previously unreported, common, transient asymptomatic pulmonary opacities (TAPOs) were noted at the University of Colorado in patients during osimertinib therapy. Methods CT imaging and clinical notes of NSCLC patients treated at the University of Colorado with osimertinib were retrospectively reviewed. Results Seven of twenty patients (35%), developed TAPOs while on osimertinib. The radiological patterns seen included ground-glass opacities with/without nodular consolidation. The median time to first lesion development was 8.7 weeks (range: 1.6 – 43 weeks) and 6 weeks (range: 1 – 11 weeks) to resolution during continued osimertinib. Conclusions TAPOs may be a previously unrecognized, benign feature associated with osimertinib therapy, which may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic, localized and there is no evidence of disease progression elsewhere it may be reasonable to continue treatment with osimertinib and monitor these lesions for resolution. PMID:27618759

BACE1 inhibition more effectively suppresses initiation than progression of β-amyloid pathology.

PubMed

Peters, Finn; Salihoglu, Hazal; Rodrigues, Eva; Herzog, Etienne; Blume, Tanja; Filser, Severin; Dorostkar, Mario; Shimshek, Derya R; Brose, Nils; Neumann, Ulf; Herms, Jochen

2018-05-01

BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology. The longitudinal approach allowed to assess the kinetics of individual plaques and associated presynaptic pathology, before and throughout treatment. BACE1 inhibition could not halt but slow down progressive β-amyloid deposition and associated synaptic pathology. Notably, the data revealed that the initial process of plaque formation, rather than the subsequent phase of gradual plaque growth, is most sensitive to BACE1 inhibition. This finding of particular susceptibility of plaque formation has profound implications to achieve optimal therapeutic efficacy for the prospective treatment of AD.

Clinical validation of a nanodiamond-embedded thermoplastic biomaterial

PubMed Central

Lee, Dong-Keun; Kee, Theodore; Liang, Zhangrui; Hsiou, Desiree; Miya, Darron; Wu, Brian; Osawa, Eiji; Chow, Edward Kai-Hua; Kang, Mo K.; Ho, Dean

2017-01-01

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications. PMID:29078364

Extra-articular fractures of the digital metacarpals and phalanges of the long fingers.

PubMed

Le Nen, D

2014-02-01

Metacarpal and phalangeal fractures of the long fingers are the result of trauma occurring under extremely varied circumstances. As a consequence, the clinical presentation varies greatly, with every bone and joint potentially being involved. Each step of their treatment is crucial, although the benign appearance of these injuries can lead to steps being missed: diagnostic phase with clinical examination and radiographs; therapeutic phase where the most suitable treatment is chosen, which combines mobilization of the digital chains as soon as possible and in every patient; follow-up phase with regular monitoring to detect any complications, especially secondary displacement, and verify that good progress is being made during rehabilitation. The goal of any fracture treatment is to preserve or restore the anatomy, with the emphasis here being on the stability and mobility of the digital chains. The potential progression towards serious functional sequelae (pain, instability or stiffness in hand) and the resulting significant socio-economic repercussions must be at the forefront of a surgeon's mind early on during the initial care of any finger or hand trauma. Copyright © 2014. Published by Elsevier SAS.

Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on treatment of prostate cancer

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

Price, Robert A.; Hannoun-Levi, Jean-Michel; Horwitz, Eric

2006-10-01

Purpose: The aim of this study was to evaluate the feasibility of treating the pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT) with respect to our routine acceptance criteria. Methods and Materials: A series of 10 previously treated prostate patients were randomly selected and the pelvic lymphatic regions delineated on the fused magnetic resonance/computed tomography data sets. A targeting progression was formed from the prostate and proximal seminal vesicles only to the inclusion of all pelvic lymphatic regions and presacral region resulting in 5 planning scenarios of increasing geometric difficulty. IMRT plans were generated for each stage for two acceleratormore » manufacturers. Dose volume histogram data were analyzed with respect to dose to the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis was performed for the number of segments required, monitor units, 'hot spots,' and treatment time. Results: Both rectal endpoints were met for all targets. Bladder endpoints were not met and the bowel endpoint was met in 40% of cases with the inclusion of the extended and presacral lymphatics. A significant difference was found in the number of segments and monitor units with targeting progression and between accelerators, with the smaller beamlets yielding poorer results. Treatment times between the 2 linacs did not exhibit a clinically significant difference when compared. Conclusions: Many issues should be considered with pelvic lymphatic irradiation during IMRT delivery for prostate cancer including dose per fraction, normal structure dose/volume limits, planning target volumes generation, localization, treatment time, and increased radiation leakage. We would suggest that, at a minimum, the endpoints used in this work be evaluated before beginning IMRT pelvic nodal irradiation.« less

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients.

PubMed

Hung, Yi-Ping; Chen, Ming-Huang; Lin, June-Seng; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

2018-07-01

Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation. Copyright © 2018. Published by Elsevier Taiwan LLC.

Digital monitoring and care: Virtual medicine.

PubMed

Shinbane, Jerold S; Saxon, Leslie A

2016-11-01

Remote digital health monitoring technologies can be synergistically organized to create a virtual medical system providing more continuous care centered on the patient rather than the bricks and mortar medical complex. Utilization of the digitalized patient health monitoring can facilitate diagnosis, treatment plans, physician-patient interaction, and accelerate the progress of medical research, education, and training. The field of cardiac electrophysiology has been an early adopter of this shift in care and serves as a paradigm applicable to all areas of medicine. The overall impact of this remote virtual care model on the quality of medical care and patient experience requires greater study, as well as vigilance as to the differences between technology and care in order to preserve the intangible and immeasurable factors that bring humanity to the art and science of medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical treatment and intraoperative spinal cord monitoring in scoliosis associated with chronic inflammatory demyelinating polyneuropathy: A case report

PubMed Central

Miyakoshi, Naohisa; Hongo, Michio; Kasukawa, Yuji; Ishikawa, Yoshinori; Misawa, Akiko; Shimada, Yoichi

2013-01-01

There has been only one reported case of neuromuscular scoliosis following chronic inflammatory demyelinating polyneuropathy (CIDP). However, no cases of scoliosis that were treated with surgery secondary to CIDP have been previously described. A 16-year-old boy with CIDP was consultant due to the progression of scoliosis with the coronal curve of 86° from T8 to T12. Posterior correction and fusion with segmental pedicle screws were performed under intraoperative spinal cord monitoring with transcranial electric motor-evoked potentials. Although the latency period was prolonged and amplitude was low, the potential remained stable. Coronal curve was corrected from 86° to 34° without neurological complications. We here describe scoliosis associated with CIDP, which was successfully treated with surgery under intraoperative spinal cord monitoring. PMID:23311940

Cutaneous respirometry by dynamic measurement of mitochondrial oxygen tension for monitoring mitochondrial function in vivo.

PubMed

Harms, Floor A; Voorbeijtel, Wilhelmina J; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

2013-09-01

Progress in diagnosis and treatment of mitochondrial dysfunction in chronic and acute disease could greatly benefit from techniques for monitoring of mitochondrial function in vivo. In this study we demonstrate the feasibility of in vivo respirometry in skin. Mitochondrial oxygen measurements by means of oxygen-dependent delayed fluorescence of protoporphyrin IX are shown to provide a robust basis for measurement of local oxygen disappearance rate (ODR). The fundamental principles behind the technology are described, together with an analysis method for retrievel of respirometry data. The feasibility and reproducibility of this clinically useful approach are demonstrated in a series of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

Introduction to biosensors.

PubMed

Bhalla, Nikhil; Jolly, Pawan; Formisano, Nello; Estrela, Pedro

2016-06-30

Biosensors are nowadays ubiquitous in biomedical diagnosis as well as a wide range of other areas such as point-of-care monitoring of treatment and disease progression, environmental monitoring, food control, drug discovery, forensics and biomedical research. A wide range of techniques can be used for the development of biosensors. Their coupling with high-affinity biomolecules allows the sensitive and selective detection of a range of analytes. We give a general introduction to biosensors and biosensing technologies, including a brief historical overview, introducing key developments in the field and illustrating the breadth of biomolecular sensing strategies and the expansion of nanotechnological approaches that are now available. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

PubMed Central

Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

2014-01-01

Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

Synthesis of current knowledge on post-fire seeding for soil stabilization and invasive species control

USGS Publications Warehouse

Beyers, Jan L.; Pyke, David A.; Wirth, Troy

2015-01-01

The General Accounting Office has identified a need for better information on the effectiveness of post-fire emergency stabilization and rehabilitation methods used by the U.S. Forest Service and Department of Interior (DOI) agencies. Since reviews were published on treatment effectiveness in the early 2000s, treatment choices have changed and increased monitoring has been done. Greater use of native species has added substantially to burned area emergency response (BAER) treatment costs, for example, but quantitative data on this treatment were scarce in earlier reviews. We synthesized current information on the effectiveness of post-fire seeding for both soil stabilization and for prevention of the spread of invasive species in rangelands. We reviewed published literature (peer-reviewed and “gray”) and agency monitoring reports, as well as compiled and analyzed quantitative data in agency files. Products of this review include a web-accessible database of monitoring reports and published information, a scientific journal paper summarizing findings of scientific studies, an annotated bibliography of peer-reviewed papers, a summary report published as a General Technical Report that will be available online (in progress), and presentations to scientific meetings and BAER/ESR team training sessions and workshops. By combining results from studies done by Forest Service and DOI agency personnel with research studies published since the initial reviews, we presented a comprehensive synthesis of seeding effectiveness knowledge that complements the review of other hillslope treatments published by other researchers. This information will help federal land managers make more cost-effective decisions on post-fire stabilization and rehabilitation treatments.

Speech in spinocerebellar ataxia.

PubMed

Schalling, Ellika; Hartelius, Lena

2013-12-01

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant cerebellar ataxias clinically characterized by progressive ataxia, dysarthria and a range of other concomitant neurological symptoms. Only a few studies include detailed characterization of speech symptoms in SCA. Speech symptoms in SCA resemble ataxic dysarthria but symptoms related to phonation may be more prominent. One study to date has shown an association between differences in speech and voice symptoms related to genotype. More studies of speech and voice phenotypes are motivated, to possibly aid in clinical diagnosis. In addition, instrumental speech analysis has been demonstrated to be a reliable measure that may be used to monitor disease progression or therapy outcomes in possible future pharmacological treatments. Intervention by speech and language pathologists should go beyond assessment. Clinical guidelines for management of speech, communication and swallowing need to be developed for individuals with progressive cerebellar ataxia. Copyright © 2013 Elsevier Inc. All rights reserved.

Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.

PubMed

Horovitz, Dafne D G; Magalhães, Tatiana S P C; Acosta, Angelina; Ribeiro, Erlane M; Giuliani, Liane R; Palhares, Durval B; Kim, Chong A; de Paula, Ana Carolina; Kerstenestzy, Marcelo; Pianovski, Mara A D; Costa, Maria Ione F; Santos, Francisca C; Martins, Ana Maria; Aranda, Carolina S; Correa Neto, Jordão; Holanda, Gervina Brady Moreira; Cardoso, Laércio; da Silva, Carlos A B; Bonatti, Renata C F; Ribeiro, Bethania F R; Rodrigues, Maria do Carmo S; Llerena, Juan C

2013-05-01

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age. Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated. A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved. The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population. Copyright © 2013 Elsevier Inc. All rights reserved.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

Salmon Supplementation Studies in Idaho Rivers, 1996-1998 Progress Report.

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

Reighn, Christopher A.; Lewis, Bert; Taki, Doug

1999-06-01

Information contained in this report summarizes the work that has been done by the Shoshone-Bannock Tribes Fisheries Department under BPA Project No. 89-098-3, Contract Number 92-BI-49450. Relevant data generated by the Shoshone-Bannock Tribe will be collated with other ISS cooperator data collected from the Salmon and Clearwater rivers and tributary streams. A summary of data presented in this report and an initial project-wide level supplementation evaluation will be available in the ISS 5 year report that is currently in progress. The Shoshone-Bannock Tribal Fisheries Department is responsible for monitoring a variety of chinook salmon (Oncorhynchus tshawytscha) production parameters as partmore » of the Idaho Supplementation Studies (BPA Project No. 89-098-3, Contract Number 92-BI-49450). Parameters include parr abundance in tributaries to the upper Salmon River; adult chinook salmon spawner abundance, redd counts, and carcass collection. A rotary screw trap is operated on the East Fork Salmon River and West Fork Yankee Fork Salmon River to enumerate and PIT-tag chinook smolts. These traps are also used to monitor parr movement, and collect individuals for the State and Tribal chinook salmon captive rearing program. The SBT monitors fisheries parameters in the following six tributaries of the Salmon River: Bear Valley Creek, East Fork Salmon River, Herd Creek, South Fork Salmon River, Valley Creek, and West Fork Yankee Fork. Chinook populations in all SBT-ISS monitored streams continue to decline. The South Fork Salmon River and Bear Valley Creek have the strongest remaining populations. Snorkel survey methodology was used to obtain parr population estimates for ISS streams from 1992 to 1997. Confidence intervals for the parr population estimates were large, especially when the populations were low. In 1998, based on ISS cooperator agreement, snorkeling to obtain parr population estimates was ceased due to the large confidence intervals. A rotary screw trap was operated on the West Fork Yankee Fork during the spring, summer, and fall of 1998 to monitor juvenile chinook migration. A screw trap was also operated on the East Fork of the Salmon River during the spring and fall from 1993 to 1997. Supplementation treatments have occurred on the South Fork Salmon River (IDFG), the East Fork Salmon River (EFSR), and the West Fork Yankee Fork of the Salmon River (WFYF). The EFSR received supplementation treatments yearly through 1995. There have been no treatments since 1995, and no significant future treatments from local broodstock are planned due to extremely poor escapement. The WFYF received a single presmolt treatment in 1994. There was an egg and adult release treatment in 1998 from the captive rearing program, not part of the original ISS study. Similarly, no significant future treatments are planned for the West Fork Yankee Fork due to extremely poor escapement. However, small scale experimental captive rearing and broodstock techniques are currently being tested with populations from the EFSR and WFYF. Captive rearing/broodstock techniques could potentially provide feedback for evaluation of supplementation. The other three SBT-ISS streams are control streams and do not receive supplementation treatments.« less

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease

PubMed Central

Zeestraten, Eva Anna; Benjamin, Philip; Lambert, Christian; Lawrence, Andrew John; Williams, Owen Alan; Morris, Robin Guy; Barrick, Thomas Richard; Markus, Hugh Stephen

2016-01-01

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI’s potential as surrogate marker for SVD. PMID:26808982

A joint estimation detection of Glaucoma progression in 3D spectral domain optical coherence tomography optic nerve head images

NASA Astrophysics Data System (ADS)

Belghith, Akram; Bowd, Christopher; Weinreb, Robert N.; Zangwill, Linda M.

2014-03-01

Glaucoma is an ocular disease characterized by distinctive changes in the optic nerve head (ONH) and visual field. Glaucoma can strike without symptoms and causes blindness if it remains without treatment. Therefore, early disease detection is important so that treatment can be initiated and blindness prevented. In this context, important advances in technology for non-invasive imaging of the eye have been made providing quantitative tools to measure structural changes in ONH topography, an essential element for glaucoma detection and monitoring. 3D spectral domain optical coherence tomography (SD-OCT), an optical imaging technique, has been commonly used to discriminate glaucomatous from healthy subjects. In this paper, we present a new framework for detection of glaucoma progression using 3D SD-OCT images. In contrast to previous works that the retinal nerve fiber layer (RNFL) thickness measurement provided by commercially available spectral-domain optical coherence tomograph, we consider the whole 3D volume for change detection. To integrate a priori knowledge and in particular the spatial voxel dependency in the change detection map, we propose the use of the Markov Random Field to handle a such dependency. To accommodate the presence of false positive detection, the estimated change detection map is then used to classify a 3D SDOCT image into the "non-progressing" and "progressing" glaucoma classes, based on a fuzzy logic classifier. We compared the diagnostic performance of the proposed framework to existing methods of progression detection.

A joint estimation detection of Glaucoma progression in 3D spectral domain optical coherence tomography optic nerve head images.

PubMed

Belghith, Akram; Bowd, Christopher; Weinreb, Robert N; Zangwill, Linda M

2014-03-18

Glaucoma is an ocular disease characterized by distinctive changes in the optic nerve head (ONH) and visual field. Glaucoma can strike without symptoms and causes blindness if it remains without treatment. Therefore, early disease detection is important so that treatment can be initiated and blindness prevented. In this context, important advances in technology for non-invasive imaging of the eye have been made providing quantitative tools to measure structural changes in ONH topography, an essential element for glaucoma detection and monitoring. 3D spectral domain optical coherence tomography (SD-OCT), an optical imaging technique, has been commonly used to discriminate glaucomatous from healthy subjects. In this paper, we present a new framework for detection of glaucoma progression using 3D SD-OCT images. In contrast to previous works that the retinal nerve fiber layer (RNFL) thickness measurement provided by commercially available spectral-domain optical coherence tomograph, we consider the whole 3D volume for change detection. To integrate a priori knowledge and in particular the spatial voxel dependency in the change detection map, we propose the use of the Markov Random Field to handle a such dependency. To accommodate the presence of false positive detection, the estimated change detection map is then used to classify a 3D SDOCT image into the "non-progressing" and "progressing" glaucoma classes, based on a fuzzy logic classifier. We compared the diagnostic performance of the proposed framework to existing methods of progression detection.

Youth Codesign of a Mobile Phone App to Facilitate Self-Monitoring and Management of Mood Symptoms in Young People With Major Depression, Suicidal Ideation, and Self-Harm.

PubMed

Hetrick, Sarah Elisabeth; Robinson, Jo; Burge, Eloise; Blandon, Ryan; Mobilio, Bianca; Rice, Simon M; Simmons, Magenta B; Alvarez-Jimenez, Mario; Goodrich, Simon; Davey, Christopher G

2018-01-23

Effective treatment of depression in young people is critical, given its prevalence, impacts, and link to suicide. Clinical practice guidelines point to the need for regular monitoring of depression symptom severity and the emergence of suicidal ideation to track treatment progress and guide intervention delivery. Yet, this is seldom integrated in clinical practice. The objective of this study was to address the gap between guidelines about monitoring and real-world practice by codesigning an app with young people that allows for self-monitoring of mood and communication of this monitoring with a clinician. We engaged young people aged 18 to 25 years who had experienced depression, suicidal ideation including those who self-harm, as well as clinicians in a codesign process. We used a human-centered codesign design studio methodology where young people designed the features of the app first individually and then as a group. This resulted in a minimal viable product design, represented through low-fidelity hand-drawn wireframes. Clinicians were engaged throughout the process via focus groups. The app incorporated a mood monitoring feature with innovative design aspects that allowed customization, and was named a "well-being tracker" in response to the need for a positive approach to this function. Brief personalized interventions designed to support young people in the intervals between face-to-face appointments were embedded in the app and were immediately available via pop-ups generated by a back-end algorithm within the well-being tracker. Issues regarding the safe incorporation of alerts generated by the app into face-to-face clinical services were raised by clinicians (ie, responding in a timely manner) and will need to be addressed during the full implementation of the app into clinical services. The potential to improve outcomes for young people via technology-based enhancement to interventions is enormous. Enhancing communication between young people and their clinicians about symptoms and treatment progress and increasing access to timely and evidence-based interventions are desirable outcomes. To achieve positive outcomes for young people using technology- (app) based interventions, it is critical to understand and incorporate, in a meaningful way, the expectations and motivations of both young people and clinicians. ©Sarah Elisabeth Hetrick, Jo Robinson, Eloise Burge, Ryan Blandon, Bianca Mobilio, Simon M Rice, Magenta B Simmons, Mario Alvarez-Jimenez, Simon Goodrich, Christopher G Davey. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.01.2018.

Rare presentation of intractable tuberculous panophthalmitis with intraocular and intraorbital abscesses: a case report.

PubMed

Boonsopon, Sutasinee; Tesavibul, Nattaporn; Uiprasertkul, Mongkol; Leeamornsiri, Supinda; Choopong, Pitipol

2017-07-04

We report a rare presentation of extrapulmonary tuberculosis. A 29-year-old Burmese woman with human immunodeficiency virus infection and known pulmonary tuberculosis who had been treated for 5 months presented to our hospital with unilateral progressive painful visual loss of 1 month's duration. She was diagnosed with tuberculous panophthalmitis with subretinal and intraorbital abscesses, conjunctival abscess, and extraocular muscle tuberculoma. The diagnosis was confirmed by a conjunctival pus swab with a positive result for acid-fast bacilli and a positive result for a mycobacterial culture. There was high suspicion of multidrug-resistant tuberculosis. Despite receiving ongoing aggressive treatment with conventional antituberculous medications, this patient required subtotal orbital exenteration to control her infection and prevent further progression. Second-line antituberculous medications were added to the first-line therapy, with satisfactory results achieved. Tuberculous panophthalmitis with intraocular and intraorbital abscesses is a rare presentation of extrapulmonary tuberculosis. Patients who do not respond to first-line antituberculous therapy might be infected with either single-drug or multidrug-resistant Mycobacterium tuberculosis. Patient compliance is one of the key factors that can alter the course of treatment. Careful patient monitoring can improve disease progression, outcome, and prognosis.

Construction of a Cerebral Hemorrhage Test System Operated in Real-time

NASA Astrophysics Data System (ADS)

Li, Gen; Sun, Jian; Ma, Ke; Yan, Qingguang; Zheng, Xiaolin; Qin, Mingxin; Jin, Gui; Ning, Xu; Zhuang, Wei; Feng, Hua; Huang, Shiyuwei

2017-02-01

The real-time monitoring and evaluation of the severity and progression of cerebral hemorrhage is essential to its intensive care and its successful emergency treatment. Based on magnetic induction phase shift technology combined with a PCI data acquisition system and LabVIEW software, this study established a real-time monitoring system for cerebral hemorrhage. To test and evaluate the performance of the system, the authors performed resolution conductivity experiments, salted water simulation experiments and cerebral hemorrhage experiments in rabbits and found that when the conductivity difference was 0.73 S/m, the phase difference was 13.196°. The phase difference change value was positively proportional to the volume of saline water, and the conductivity value was positively related to the phase difference of liquid under the same volume conditions. After injecting 3 mL blood into six rabbits, the average change in the blood phase difference was -2.03783 ± 0.22505°, and it was positively proportional to the volume of blood, which was consistent with the theoretical results. The results show that the system can monitor the progressive development of cerebral hemorrhage in real-time and has the advantages of low cost, small size, high phase accuracy, and good clinical application potentiality.

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Optical imaging: new tools for arthritis.

PubMed

Chamberland, David; Jiang, Yebin; Wang, Xueding

2010-10-01

Conventional radiography, ultrasound, CT, MRI, and nuclear imaging are the current imaging modalities used for clinical evaluation of arthritis which is highly prevalent and a leading cause of disability. Some of these types of imaging are also used for monitoring disease progression and treatment response of arthritis. However, their disadvantages limit their utilities, such as ionizing radiation for radiography, CT, and nuclear imaging; suboptimal tissue contrast resolution for radiography, CT, ultrasound, and nuclear imaging; high cost for CT and MRI and nuclear imaging; and long data-acquisition time with ensuing patient discomfort for MRI. Recently, there have been considerable advances in nonionizing noninvasive optical imaging which has demonstrated promise for early diagnosis, monitoring therapeutic interventions and disease progression of arthritis. Optical based molecular imaging modalities such as fluorescence imaging have shown high sensitivity in detection of optical contrast agents and can aid early diagnosis and ongoing evaluation of chronic inflammatory arthritis. Optical transillumination imaging or diffuse optical tomography may differentiate normal joint clear synovial fluid from turbid and pink medium early in the inflammatory process. Fourier transform infrared spectroscopy has been used to evaluate fluid composition from joints affected by arthritis. Hemodynamic changes such as angiogenesis, hypervascularization, and hypoxia in arthritic articular tissue can potentially be observed by diffuse optical tomography and photoacoustic tomography. Optical measurements could also facilitate quantification of hemodynamic properties such as blood volume and oxygenation levels at early stages of inflammatory arthritis. Optical imaging provides methodologies which should contribute to detection of early changes and monitoring of progression in pathological characteristics of arthritis, with relatively simple instrumentation.

Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

PubMed Central

Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

2015-01-01

Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

[Progressive damage monitoring of corrugated composite skins by the FBG spectral characteristics].

PubMed

Zhang, Yong; Wang, Bang-Feng; Lu, Ji-Yun; Gu, Li-Li; Su, Yong-Gang

2014-03-01

In the present paper, a method of monitoring progressive damage of composite structures by non-uniform fiber Bragg grating (FBG) reflection spectrum is proposed. Due to the finite element analysis of corrugated composite skins specimens, the failure process under tensile load and corresponding critical failure loads of corrugated composite skin was predicated. Then, the non-uniform reflection spectrum of FBG sensor could be reconstructed and the corresponding relationship between layer failure order sequence of corrugated composite skin and FBG sensor reflection spectrums was acquired. A monitoring system based on FBG non-uniform reflection spectrum, which can be used to monitor progressive damage of corrugated composite skins, was built. The corrugated composite skins were stretched under this FBG non-uniform reflection spectrum monitoring system. The results indicate that real-time spectrums acquired by FBG non-uniform reflection spectrum monitoring system show the same trend with the reconstruction reflection spectrums. The maximum error between the corresponding failure and the predictive value is 8.6%, which proves the feasibility of using FBG sensor to monitor progressive damage of corrugated composite skin. In this method, the real-time changes in the FBG non-uniform reflection spectrum within the scope of failure were acquired through the way of monitoring and predicating, and at the same time, the progressive damage extent and layer failure sequence of corru- gated composite skin was estimated, and without destroying the structure of the specimen, the method is easy and simple to operate. The measurement and transmission section of the system are completely composed of optical fiber, which provides new ideas and experimental reference for the field of dynamic monitoring of smart skin.

Teacher Progress Monitoring of Instructional and Behavioral Management Practices: An Evidence-Based Approach to Improving Classroom Practices

ERIC Educational Resources Information Center

Reddy, Linda A.; Dudek, Christopher M.

2014-01-01

In the era of teacher evaluation and effectiveness, assessment tools that identify and monitor educators' instruction and behavioral management practices are in high demand. The Classroom Strategies Scale (CSS) Observer Form is a multidimensional teacher progress monitoring tool designed to assess teachers' usage of instructional and behavioral…

Dynamics of muscle strength improvement during isokinetic rehabilitation of athletes with ACL rupture and chondromalacia patellae.

PubMed

Desnica Bakrac, N

2003-03-01

To assess quantitatively dynamics and extent of the increase in muscle strength during isokinetic rehabilitation. daily measurements of muscle strength; detailed testing at the beginning and at the end of rehabilitation. Cybex Rehabilitation Center, Zagreb. 44 athletes (31 m, 13 F, age 16-35), 3 injury-defined groups: athletes with ACL rupture (non-reconstructed and reconstructed) and chondromalacia patellae. all subjects underwent isokinetic rehabilitation on Cybex Orthotron KT2 device, using individually designed protocols (extension and flexion exercises, concentric muscle contractions, 15 treatments). monitoring of daily progress on rehabilitation device and detailed testing on diagnostic device. All patients showed considerable improvement. Muscle strength improved on average 141% (SD=110) in ACL-reconstructed group, 144% (SD=130) for chondromalacia patellae group and 150% (SD=74) for ACL-non-reconstructed group, comparing to initial strength. Dynamic status tested on Cybex Otrhotron diagnostic device prior and after rehabilitation strongly correlated with final progress monitored on the rehabilitation device. Isokinetic rehabilitation is a quick and effective method in treating knee injuries in athletes. Both types of objective criteria have shown significant increase in muscle strength. The improvement of muscle strength was on the average 149% (SD=101), which is about 10% daily for 15 treatments. The greatest progress, 19% per day, occurred during first five days. The athletes were able to resume their sport activities as follows: patients from chondromalacia patellae group, and most of them from the non-reconstructed ACL group were back in competition within a month, while 75% from the ACL reconstructed group came back within 3 months, and the rest of them within 5 months.

ELF (Extremely Low Frequency) Communications System - Ecological Monitoring Program: Summary of 1988 Progress

DTIC Science & Technology

1989-11-01

of fresh leaves are fast at both sites. 3 Similar comparisons using autumn abscised leaves show intermediate processing rates at the treatment site...processing fresh or autumn- abscised leaves during 1988 (t-test). Analyses of variance showed that fresh leaves were pricessed significantly faster at the...Northern Journal of Applied Forestry, 5:14, 1988. 22 Connaughton, P. The effects of acid precipi*ation on nutrient levels in a forest soil and foliage of

[Cardiovascular management of patients with chronic myeloid leukemia from a multidisciplinary perspective, and proposing action protocol by consensus meeting].

PubMed

García-Gutiérrez, Valentín; Jiménez-Velasco, Antonio; Gómez-Casares, M Teresa; Sánchez-Guijo, Fermín; López-Sendón, Jose Luis; Steegmann Olmedillas, Juan Luis

2016-06-17

The second generation tyrosine kinase inhibitors (TKI, dasatinib and nilotinib) used in chronic myeloid leukemia (CML) treatment have shown a benefit compared to imatinib in responses achieved and disease progression. However, both have been related to some cardiovascular toxicity, being more frequent in patients with cardiovascular risk factors (CVRFs). Nowadays, due to the lack of recommendations for CML patients, CVRF management is carried out heterogeneously. The aim of this work is to develop recommendations on the prevention and monitoring of cardiovascular events (CVD) in patients with CML treated with TKIs. Experts from the Spanish Group of Chronic Myeloid Leukemia together with experts in cardiovascular risk have elaborated, after a consensus meeting, recommendations for the prevention and follow-up of CVE in patients with CML treated with TKI. Recommendations regarding the necessary information to be collected on clinical history, treatment decisions, as well as treatment and monitoring of CVRFs are shown in this document. TKI treatment requires comprehensive patient management from a multidisciplinary approach, in which both the prevention and management of CVRFs are essential. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

The National Institutes of Health Affordable Cancer Technologies Program: Improving Access to Resource-Appropriate Technologies for Cancer Detection, Diagnosis, Monitoring, and Treatment in Low- and Middle-Income Countries

PubMed Central

Divi, Rao; Gwede, Michael; Tandon, Pushpa; Sorg, Brian S.; Ossandon, Miguel R.; Agrawal, Lokesh; Pai, Vinay; Baker, Houston; Lash, Tiffani Bailey

2016-01-01

Point-of-care (POC) technologies have proved valuable in cancer detection, diagnosis, monitoring, and treatment in the developed world, and have shown promise in low-and-middle-income countries (LMIC) as well. Despite this promise, the unique design constraints presented in low-resource settings, coupled with the variety of country-specific regulatory and institutional dynamics, have made it difficult for investigators to translate successful POC cancer interventions to the LMIC markets. In response to this need, the National Cancer Institute has partnered with the National Institute of Biomedical Imaging and Bioengineering to create the National Institutes of Health Affordable Cancer Technologies (ACTs) program. This program seeks to simplify the pathway to market by funding multidisciplinary investigative teams to adapt and validate the existing technologies for cancer detection, diagnosis, and treatment in LMIC settings. The various projects under ACTs range from microfluidic cancer diagnostic tools to novel treatment devices, each geared for successful clinical adaptation to LMIC settings. Via progression through this program, each POC innovation will be uniquely leveraged for successful clinical translation to LMICs in a way not before seen in this arena. PMID:27730015

A pilot investigation of a mobile phone application and progressive reminder system to improve adherence to daily prevention treatment in adolescents and young adults with migraine.

PubMed

Ramsey, Rachelle R; Holbein, Christina E; Powers, Scott W; Hershey, Andrew D; Kabbouche, Marielle A; O'Brien, Hope L; Kacperski, Joanne; Shepard, Jeffrey; Hommel, Kevin A

2018-01-01

Background Effective management of migraine requires adherence to treatment recommendations; however, adolescents with migraine take their daily medications only 75% of the time. Low-cost adherence-focused interventions using technology may improve adherence, but have not been investigated. Methods Thirty-five adolescents and young adults (13-21 years) with migraine participated in an AB-design pilot study to assess the use of a mobile phone adherence-promotion application ("app") and progressive reminder system. Adherence was calculated using electronic monitoring during the baseline period and medication adherence intervention. Results Relative to baseline, adherence significantly improved during the first month of the intervention. Specifically, improvements existed for older participants with lower baseline adherence. Self-reported app-based adherence rates were significantly lower than electronically monitored adherence rates. Participants rated the intervention as acceptable and easy to use. Conclusions "Apps" have the potential to improve medication adherence and are a promising intervention for adolescents and young adults with low adherence. Involving parents in the intervention is also helpful. Providers should assess barriers to adherence and use of technology-based interventions, encourage parents to incorporate behavioral incentives, and provide referrals for more intensive interventions to improve long-term outcomes. Further, tracking adherence in an app may result in an underestimation of adherence. Future full-scale studies should be conducted to examine adherence promotion app interventions.

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 1-Mechanisms, Efficacy, and Safety.

PubMed

McNamara, C; Sugrue, G; Murray, B; MacMahon, P J

2017-09-01

Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications. An understanding of the new generation of MS drugs in conjunction with the key role that MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse events is of vital importance to the radiologist and clinical physician alike. Radiologists are in a unique position to detect many of the described complications well in advance of clinical symptoms. Part 1 of this review outlines recent developments in the treatment of MS and discusses the published clinical data on the efficacy and safety of the currently approved and emerging therapies in this condition as they apply to the radiologist. Part 2 will cover pharmacovigilance and the role the neuroradiologist plays in monitoring patients for signs of opportunistic infection and/or disease progression. © 2017 by American Journal of Neuroradiology.

Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

PubMed Central

Boerma, J. Ties; Stanecki, Karen A.; Newell, Marie-Louise; Luo, Chewe; Beusenberg, Michel; Garnett, Geoff P.; Little, Kirsty; Calleja, Jesus Garcia; Crowley, Siobhan; Kim, Jim Yong; Zaniewski, Elizabeth; Walker, Neff; Stover, John; Ghys, Peter D.

2006-01-01

This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment. PMID:16501733

Blood-based analyses of cancer: Circulating myeloid-derived suppressor cells - is a new era coming?

PubMed

Okla, Karolina; Wertel, Iwona; Wawruszak, Anna; Bobiński, Marcin; Kotarski, Jan

2018-06-21

Progress in cancer treatment made by the beginning of the 21st century has shifted the paradigm from one-size-fits-all to tailor-made treatment. The popular vision, to study solid tumors through the relatively noninvasive sampling of blood, is one of the most thrilling and rapidly advancing fields in global cancer diagnostics. From this perspective, immune-cell analysis in cancer could play a pivotal role in oncology practice. This approach is driven both by rapid technological developments, including the analysis of circulating myeloid-derived suppressor cells (cMDSCs), and by the increasing application of (immune) therapies, the success or failure of which may depend on effective and timely measurements of relevant biomarkers. Although the implementation of these powerful noninvasive diagnostic capabilities in guiding precision cancer treatment is poised to change the ways in which we select and monitor cancer therapy, challenges remain. Here, we discuss the challenges associated with the analysis and clinical aspects of cMDSCs and assess whether the problems in implementing tumor-evolution monitoring as a global tool in personalized oncology can be overcome.

Ultrasonic Monitoring of the Progress of Lactic Acid Fermentation

NASA Astrophysics Data System (ADS)

Masuzawa, Nobuyoshi; Kimura, Akihiro; Ohdaira, Etsuzo

2003-05-01

Promotion of lactic acid fermentation by ultrasonic irradiation has been attempted. It is possible to determine the progress of fermentation and production of a curd, i.e., yoghurt and or kefir, by measuring acidity using a pH meter. However, this method is inconvenient and indirect for the evaluation of the progress of lactic acid fermentation under anaerobic condition. In this study, an ultrasonic monitoring method for evaluating the progress of lactic acid fermentation was examined.

Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report.

PubMed

Hopps, S; Roach, A; Yuen, C; Borders, E

2015-02-01

Eumycetoma is a chronic infection of the skin and subcutaneous tissue caused by filamentous fungi, which usually occurs in tropical or subtropical countries. We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole. The use of voriconazole and liposomal amphotericin B halted the progression and allowed gradual resolution of the infection. The patient will require close monitoring and long-term therapy with voriconazole to obtain a clinical cure. Voriconazole and liposomal amphotericin B are potential initial treatment options, with long-term voriconazole maintenance therapy, for an Aspergillus-induced eumycetoma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases.

PubMed

Morita, Naoki; Haga, Sanae; Ohmiya, Yoshihiro; Ozaki, Michitaka

2016-03-15

We propose a new concept of tumor progression monitoring using dual luciferases in living animals to reduce stress for small animals and the cost of luciferin. The secreted Cypridina luciferase (CLuc) was used as an ex vivo indicator to continuously monitor tumor progression. On the other hand, the non-secreted firefly luciferase was used as an in vivo indicator to analyze the spatial distribution of the tumor at suitable time points indicated by CLuc. Thus, the new monitoring systems that use dual luciferases are available, allowing long-term bioluminescence imaging under minimal stress for the experimental animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring the progression of erosive tooth wear (ETW) using BEWE index in casts and their 3D images: A retrospective longitudinal study.

PubMed

Marro, Francisca; De Lat, Liesa; Martens, Luc; Jacquet, Wolfgang; Bottenberg, Peter

2018-04-13

To determine if the Basic erosive tooth wear index (BEWE index) is able to assess and monitor ETW changes in two consecutive cast models, and detect methodological differences when using the corresponding 3D image replicas. A total of 480 pre-treatment and 2-year post-treatment orthodontic models (n = 240 cast models and n = 240 3D image replicas) from 120 adolescents treated between 2002 and 2013 at the Gent Dental Clinic, Belgium, were scored using the BEWE index. For data analysis only posterior sextants were considered, and inter-method differences were evaluated using Wilcoxon Signed Rank test, Kappa values and Mc Nemar tests (p < 0.05). Correlations between methods were determined using Kendall tau correlation test. Significant changes of ETW were detected between two consecutive models when BEWE index was used to score cast models or their 3D image replicas (p < 0.001). A strong significant correlation (τb: 0.74; p < 0.001) was shown between both methods However, 3D image-BEWE index combination showed a higher probability for detecting initial surface changes, and scored significantly higher than casts (p < 0.001). Incidence and progression of ETW using 3D images was 13.3% (n = 16) and 60.9% (n = 56) respectively, with two subjects developing BEWE = 3 in at least one tooth surface. BEWE index is a suitable tool for the scoring of ETW lesions in 3D images and cast. The combination of both digital 3D records and index, can be used for the monitoring of ETW in a longitudinal approach. The higher sensibility of BEWE index when scoring 3D images might improve the early diagnosis of ETW lesions. The BEWE index combined with digital 3D records of oral conditions might improve the practitioner performance with respect to early diagnosis, monitoring and managing ETW. Copyright © 2018 Elsevier Ltd. All rights reserved.

Curriculum-Based Measurement of Oral Reading: Multi-Study Evaluation of Schedule, Duration, and Dataset Quality on Progress Monitoring Outcomes

ERIC Educational Resources Information Center

Christ, Theodore J.; Zopluoglu, Cengiz; Monaghen, Barbara D.; Van Norman, Ethan R.

2013-01-01

Curriculum-Based Measurement of Oral Reading (CBM-R) is used to collect time series data, estimate the rate of student achievement, and evaluate program effectiveness. A series of 5 studies were carried out to evaluate the validity, reliability, precision, and diagnostic accuracy of progress monitoring across a variety of progress monitoring…

Testing the Importance of Individual Growth Curves in Predicting Performance on a High-Stakes Reading Comprehension Test in Florida. REL 2014-006

ERIC Educational Resources Information Center

Petscher, Yaacov; Kershaw, Sarah; Koon, Sharon; Foorman, Barbara R.

2014-01-01

Districts and schools use progress monitoring to assess student progress, to identify students who fail to respond to intervention, and to further adapt instruction to student needs. Researchers and practitioners often use progress monitoring data to estimate student achievement growth (slope) and evaluate changes in performance over time for…

Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database.

PubMed

Kariminia, Azar; Durier, Nicolas; Jourdain, Gonzague; Saghayam, Suneeta; Do, Chau V; Nguyen, Lam Van; Hansudewechakul, Rawiwan; Lumbiganon, Pagakrong; Chokephaibulkit, Kulkanya; Truong, Khanh Huu; Sirisanthana, Virat; Ung, Vibol; Vonthanak, Saphonn; Ananworanich, Jintanat; Nik Yusoff, Nik Khairulddin; Kurniati, Nia; Azahar Razali, Kamarul; Fong, Moy Siew; Nallusamy, Revathy; Wati, Dewi Kumara

2014-09-01

To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART). We used Cox regression to analyze data of a cohort of Asian children. A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART. Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

THE MANAGEMENT OF AN ORAL ANAPLASTIC SARCOMA IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) USING INTRALESIONAL CHEMOTHERAPY.

PubMed

Franklinos, Lydia H V; Masters, Nicholas; Feltrer, Yedra; Pocknell, Ann; Bolt, David M; Dakin, Stephanie; Berry, Karla; Molenaar, Fieke M

2017-03-01

An adult female captive pygmy hippopotamus (Choeropsis liberiensis) was diagnosed with an oral anaplastic sarcoma. The tumor was surgically debulked and intralesional chemotherapy with mitomycin C (0.4 mg/cm 3 of tumor) and cisplatin (1 mg/cm 3 of tumor) was administered. Chemotherapeutic treatment proved difficult due to the risks of repeated anesthetics and unknown drug efficacies. Marked proliferation of the mass was observed during estrus, and chemotherapy was repeated as an experimental treatment to slow tumor progression in order for the animal to remain in the species breeding program. Tumor proliferation was detected during the first trimester of pregnancy; however, in the lactation period, the mass became quiescent. No adverse reactions to chemotherapeutic drugs were observed and the animal continues to be monitored for tumor progression. This is the first report of an anaplastic sarcoma and of chemotherapy use in a pygmy hippopotamus and it highlights logistical considerations for treating neoplasia in this species.

[Hemodialysis in patients with chronic renal insufficiency].

PubMed

Canaud, Bernard; Leray-Moragués, Hélène; Chenine-Koualef, Leila; Patrier, Laure

2012-01-01

Hemodialysis is the most advanced form of artificial renal support. It ensures the survival of almost 2 million patients wordwide. Considerable progress has been made in recent years thanks to a better understanding of uremia, optimization of treatment modalities and more personalized treatment schedules. Increase of uremic toxins removal, improvement of hemodynamic tolerance of the sessions, reduction of proinflammatory reactions due to the bioincompatibility system are major advances that may explain the reduction of morbidity and mortality in dialysis patients. New technologies (nanotechnology, biotechnology, microelectronics) are now expected to introduce further progresses by miniaturizing devices and providing them with an "artificial intelligence" capable of interacting with the patient. The main obstacle remains ageing of uremic patients, increasing prevalence of comorbidities and shortage of social resources that are not conducive to innovation. By promoting a more physiological, longer and more effective hemodialysis performed at home with help of teledialysis monitoring that would probably be an interesting option to evaluate on a medico-economical point of view.

Recent Progress on Piezoelectric and Triboelectric Energy Harvesters in Biomedical Systems

PubMed Central

Zheng, Qiang; Shi, Bojing; Wang, Zhong Lin

2017-01-01

Implantable medical devices (IMDs) have become indispensable medical tools for improving the quality of life and prolonging the patient's lifespan. The minimization and extension of lifetime are main challenges for the development of IMDs. Current innovative research on this topic is focused on internal charging using the energy generated by the physiological environment or natural body activity. To harvest biomechanical energy efficiently, piezoelectric and triboelectric energy harvesters with sophisticated structural and material design have been developed. Energy from body movement, muscle contraction/relaxation, cardiac/lung motions, and blood circulation is captured and used for powering medical devices. Other recent progress in this field includes using PENGs and TENGs for our cognition of the biological processes by biological pressure/strain sensing, or direct intervention of them for some special self‐powered treatments. Future opportunities lie in the fabrication of intelligent, flexible, stretchable, and/or fully biodegradable self‐powered medical systems for monitoring biological signals and treatment of various diseases in vitro and in vivo. PMID:28725529

In Silico Evaluation of Pharmacokinetic Optimization for Antimitogram-Based Clinical Trials.

PubMed

Haviari, Skerdi; You, Benoît; Tod, Michel

2018-04-01

Antimitograms are prototype in vitro tests for evaluating chemotherapeutic efficacy using patient-derived primary cancer cells. These tests might help optimize treatment from a pharmacodynamic standpoint by guiding treatment selection. However, they are technically challenging and require refinements and trials to demonstrate benefit to be widely used. In this study, we performed simulations aimed at exploring how to validate antimitograms and how to complement them by pharmacokinetic optimization. A generic model of advanced cancer, including pharmacokinetic-pharmacodynamic monitoring, was used to link dosing schedules with progression-free survival (PFS), as built from previously validated modules. This model was used to explore different possible situations in terms of pharmacokinetic variability, pharmacodynamic variability, and antimitogram performance. The model recapitulated tumor dynamics and standalone therapeutic drug monitoring efficacy consistent with published clinical results. Simulations showed that combining pharmacokinetic and pharmacodynamic optimization should increase PFS in a synergistic fashion. Simulated data were then used to compute required clinical trial sizes, which were 30% to 90% smaller when pharmacokinetic optimization was added to pharmacodynamic optimization. This improvement was observed even when pharmacokinetic optimization alone exhibited only modest benefit. Overall, our work illustrates the synergy derived from combining antimitograms with therapeutic drug monitoring, permitting a disproportionate reduction of the trial size required to prove a benefit on PFS. Accordingly, we suggest that strategies with benefits too small for standalone clinical trials could be validated in combination in a similar manner. Significance: This work offers a method to reduce the number of patients needed for a clinical trial to prove the hypothesized benefit of a drug to progression-free survival, possibly easing opportunities to evaluate combinations. Cancer Res; 78(7); 1873-82. ©2018 AACR . ©2018 American Association for Cancer Research.

Animal models for the study of inflammatory bowel diseases: a meta-analysis on modalities for imaging inflammatory lesions.

PubMed

Auletta, Sveva; Bonfiglio, Rita; Wunder, Andreas; Varani, Michela; Galli, Filippo; Borri, Filippo; Scimeca, Manuel; Niessen, Heiko G; Schönberger, Tanja; Bonanno, Elena

2018-03-01

Inflammatory bowel diseases are lifelong disorders affecting the gastrointestinal tract characterized by intermittent disease flares and periods of remission with a progressive and destructive nature. Unfortunately, the exact etiology is still not completely known, therefore a causal therapy to cure the disease is not yet available. Current treatment options mainly encompass the use of non-specific anti-inflammatory agents and immunosuppressive drugs that cause significant side effects that often have a negative impact on patients' quality of life. As the majority of patients need a long-term follow-up it would be ideal to rely on a non-invasive technique with good compliance. Currently, the gold standard diagnostic tools for managing IBD are represented by invasive procedures such as colonoscopy and histopathology. Nevertheless, recent advances in imaging technology continue to improve the ability of imaging techniques to non-invasively monitor disease activity and treatment response in preclinical models of IBD. Novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. Furthermore, molecular imaging advances allow us to increase our knowledge on the critical biological pathways involved in disease progression by characterizing in vivo processes at a cellular and molecular level and enabling significant improvements in the understanding of the etiology of IBD. This review presents a critical and updated overview on the imaging advances in animal models of IBD. Our aim is to highlight the potential beneficial impact and the range of applications that imaging techniques could offer for the improvement of the clinical monitoring and management of IBD patients: diagnosis, staging, determination of therapeutic targets, monitoring therapy and evaluation of the prognosis, personalized therapeutic approaches.

Post-Encephalitic Parkinsonism and Sleep Disorder Responsive to Immunological Treatment: A Case Report.

PubMed

Brunetti, Valerio; Testani, Elisa; Iorio, Raffaele; Frisullo, Giovanni; Luigetti, Marco; Di Giuda, Daniela; Marca, Giacomo Della

2016-10-01

We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control. © EEG and Clinical Neuroscience Society (ECNS) 2016.

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.

The Soluble Plasminogen Activator Receptor as a Biomarker on Monitoring the Therapy Progress of Pulmonary TB-AFB(+) Patients

PubMed Central

Mardining Raras, Tri Yudani; Noor Chozin, Iin

2010-01-01

The role of soluble soluble urokinase-type plasminogen activator receptor (suPAR) as a biological marker for TB treatment efficacy on active pulmonary TB-AFB(+) patients was investigated. Twenty pulmonary TB-AFB(+) patients participated in a cohort study for six months. The plasma suPAR level was measured using ELISA method before treatment, two months, four months and six months after treatment. At the same time clinical parameters were also measured. Results indicated that all patients (n = 20) showed highest plasma suPAR levels before treatment (median 12.775 ng/mL) and significantly decreased ( P = .0001<.05, R 2 = .890) after 2 months (median 8.019 ng/mL) and 4 months (median 5.771 ng/mL) of treatment, respectively. However, only slightly declined after 6 months therapy (median 5.009 ng/mL), near control group level (median 4.772 ng/mL). Interestingly, the significant reduced of suPAR level was parallel to treatment efficacy and correlated with other clinical and laboratory parameters, that is, decreasing of patients' complaints, increasing of BMI (r = −0.281), thoracic imaging improvement, sputum conversion, decreasing of ESR (r = 0.577) and monocytes count (r = 0.536) with exception the width of lesion in thoracic imaging. In conclusion, the suPAR level in could reflect the progress of TB therapy. PMID:22567258

Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder.

PubMed

Kalra, Amit; Roessner, Cameron; Jupp, Jennifer; Williamson, Tyler; Tellier, Raymond; Chaudhry, Ahsan; Khan, Faisal; Taparia, Minakshi; Jimenez-Zepeda, Victor H; Stewart, Douglas A; Daly, Andrew; Storek, Jan

2018-05-01

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD. We retrospectively studied 306 patients monitored for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of the monitoring in the management of PTLD. DNAemia was monitored weekly for ≥12 weeks post-transplantation. Reactivation was detected in 82% of patients. PTLD occurred in 14% of the total patients (17% of patients with reactivation). PTLD was treated with rituximab only when and if the diagnosis was established. This allowed us to evaluate potential DNAemia thresholds for pre-emptive therapy. We suggest 100,000-500,000 IU per mL whole blood as this would result in unnecessary rituximab administration to only 4-20% of patients and near zero mortality due to PTLD. After starting rituximab (for diagnosed PTLD), sustained regression of PTLD occurred in 25/25 (100%) patients in whom DNAemia became undetectable. PTLD progressed or relapsed in 12/17 (71%) patients in whom DNAemia was persistently detectable. In conclusion, for pre-emptive therapy of PTLD, we suggest threshold DNAemia of 100,000-500,000 IU/mL. Persistently detectable DNAemia after PTLD treatment with rituximab appears to have 71% positive predictive value and 100% negative predictive value for PTLD progression/relapse. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Current Approaches and Challenges for Monitoring Treatment Response in Colon and Rectal Cancer

PubMed Central

McKeown, Elizabeth; Nelson, Daniel W.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

2014-01-01

Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer. Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances. Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors. Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention. PMID:24396496

Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis.

PubMed

Hartl, Johannes; Ehlken, Hanno; Sebode, Marcial; Peiseler, Moritz; Krech, Till; Zenouzi, Roman; von Felden, Johann; Weiler-Normann, Christina; Schramm, Christoph; Lohse, Ansgar W

2017-11-24

Liver fibrosis regression but also progression may occur in patients with autoimmune hepatitis (AIH) under treatment. There is a need for non-invasive surrogate markers for fibrosis development in AIH to better guide immunosuppressive treatment. The aims of the study were to assess the impact of complete biochemical remission defined as normalisation of aminotransferases and IgG on histological activity and fibrosis development, and the value of repeat transient elastography (TE) measurement for monitoring disease progression in AIH. A total of 131 liver biopsies from 60 patients with AIH and more than 900 TE from 125 patients with AIH, 130 with primary biliary cholangitis (PBC) and 100 with primary sclerosing cholangitis (PSC), were evaluated. Time intervals between TE were at least 12 months. Patients with AIH were treated for at least six months at first TE. In contrast to PBC and PSC, a decrease of liver stiffness (LS) was observed in the whole group of patients with AIH (-6.2%/year; 95% CI -12.6% to -0.2%; p = 0.04). The largest decrease of LS was observed in patients with severe fibrosis at baseline (F4: -11.7%/year; 95% CI -19% to -3.5%; p = 0.006). Complete biochemical remission was strongly linked to regression of LS ("remission": -7.5%/year vs. "no remission": +1.7%/year, p <0.001). Similarly, complete biochemical remission predicted low histological disease activity and was the only independent predictor for histological fibrosis regression (relative risk3.66; 95% CI1.54-10.2; p = 0.001). Patients with F3/F4-fibrosis, who remained in biochemical remission showed a considerable decrease of fibrosis stage (3.7 ± 0.5 to 1.8 ± 1.7; p = 0.007) on histological follow-up. This study demonstrates that complete biochemical remission is a reliable predictor of a good prognosis in AIH and leads to fibrosis regression that can be monitored by TE. Autoimmune hepatitis is an inflammatory disease of the liver, which often progresses to cirrhosis if left untreated or in the case of insufficient treatment response. Current guidelines have defined biochemical remission (normalisation of biochemical markers for liver inflammation) as a major goal in the treatment of AIH. However, data on the prognostic relevance of this definition are scarce. Herein, we demonstrate that the current definition of biochemical remission is a reliable surrogate for low disease activity on histological assessment and for a beneficial long-term disease course. In addition, we establish transient elastography, a non-invasive ultrasound-based method of measuring scarring of liver tissue, as a reliable tool to monitor disease course in AIH. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.

PubMed

Shukla, Hem D

2017-10-25

During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein-protein interaction, and pharmacogenomics data, are indispensable to glean into the cancer genome and proteome and these approaches have generated multidimensional universal studies of genes and proteins (OMICS) data which has the potential to facilitate precision medicine. However, due to slow progress in computational technologies, the translation of big omics data into their clinical aspects have been slow. In this review, attempts have been made to describe the role of high-throughput genomic and proteomic technologies in identifying a panel of biomarkers which could be used for the early diagnosis and prognosis of cancer.

Progress Monitoring Using Direct Behavior Rating Single Item Scales in a Multiple-Baseline Design Study of the Daily Report Card Intervention

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Pyle, Kellina; Kelty, Mary Bridget; Parham, Brittany R.

2017-01-01

Direct behavior rating (DBR) may be a viable assessment for documenting current areas of impaired functioning and progress monitoring students' response to a behavioral intervention. Challenging behaviors are often addressed in general education settings using interventions such as the daily report card (DRC). To best implement and monitor such…

Monitoring Children with Reading Disabilities' Response to Phonics Intervention: Are There Differences between Intervention Aligned and General Skill Progress Monitoring Assessments?

ERIC Educational Resources Information Center

Olinghouse, Natalie G.; Lambert, Warren; Compton, Donald L.

2006-01-01

This study investigated whether 2 different progress monitoring assessments differentially predicted growth in reading skills associated with systematic phonics instruction. Oral reading fluency (ORE) was compared with an intervention aligned word list (IAWL) as predictors of growth in untimed and timed decoding and word identification and text…

Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3

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

Ulm, Franz-Josef

2000-03-31

OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3(NOTE: Part II A item 1 indicates ''PAPER'', but a report is attached electronically)

Automated Assessment of Disease Progression in Acute Myeloid Leukemia by Probabilistic Analysis of Flow Cytometry Data

PubMed Central

Rajwa, Bartek; Wallace, Paul K.; Griffiths, Elizabeth A.; Dundar, Murat

2017-01-01

Objective Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are in turn used to predict the direction of change in disease progression for each patient. Results We used 200 diseased and non-diseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (9 out of 10) for relapsing cases and 100% (26 out of 26) for the remaining cases. Conclusions We believe that these promising results are an important first step towards the development of automated predictive systems for disease monitoring and continuous response evaluation. Significance Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies. PMID:27416585

Monitoring photodynamic therapy of head and neck malignancies with optical spectroscopies

PubMed Central

Sunar, Ulas

2013-01-01

In recent years there has been significant developments in photosensitizers (PSs), light sources and light delivery systems that have allowed decreasing the treatment time and skin phototoxicity resulting in more frequent use of photodynamic therapy (PDT) in the clinical settings. Compared to standard treatment approaches such as chemo-radiation and surgery, PDT has much reduced morbidity for head and neck malignancies and is becoming an alternative treatment option. It can be used as an adjunct therapy to other treatment modalities without any additive cumulative side effects. Surface illumination can be an option for pre-malignant and early-stage malignancies while interstitial treatment is for debulking of thick tumors in the head and neck region. PDT can achieve equivalent or greater efficacy in treating head and neck malignancies, suggesting that it may be considered as a first line therapy in the future. Despite progressive development, clinical PDT needs improvement in several topics for wider acceptance including standardization of protocols that involve the same administrated light and PS doses and establishing quantitative tools for PDT dosimetry planning and response monitoring. Quantitative measures such as optical parameters, PS concentration, tissue oxygenation and blood flow are essential for accurate PDT dosimetry as well as PDT response monitoring and assessing therapy outcome. Unlike conventional imaging modalities like magnetic resonance imaging, novel optical imaging techniques can quantify PDT-related parameters without any contrast agent administration and enable real-time assessment during PDT for providing fast feedback to clinicians. Ongoing developments in optical imaging offer the promise of optimization of PDT protocols with improved outcomes. PMID:24303476

Noninvasive oxygen monitoring techniques.

PubMed

Wahr, J A; Tremper, K K

1995-01-01

As this article demonstrates, tremendous progress has been made in the techniques of oxygen measurement and monitoring over the past 50 years. From the early developments during and after World War II, to the most recent applications of solid state and microprocessor technology today, every patient in a critical care situation will have several continuous measurements of oxygenation applied simultaneously. Information therefore is available readily to alert personnel of acute problems and to guide appropriate therapy. The majority of effort to date has been placed on measuring oxygenation of arterial or venous blood. The next generation of devices will attempt to provide information about living tissue. Unlike the devices monitoring arterial or venous oxygen content, no "gold standards" exist for tissue oxygenation, so calibration will be difficult, as will interpretation of the data provided. The application of these devices ultimately may lead to a much better understanding of how disease (and the treatment of disease) alters the utilization of oxygen by the tissues.

Global AIDS Reporting-2001 to 2015: Lessons for Monitoring the Sustainable Development Goals.

PubMed

Alfvén, T; Erkkola, T; Ghys, P D; Padayachy, J; Warner-Smith, M; Rugg, D; de Lay, P

2017-07-01

Since 2001 the UNAIDS Secretariat has retained the responsibility for monitoring progress towards global commitments on HIV/AIDS. Key critical characteristics of the reporting system were assessed for the reporting period from 2004 to 2014 and analyses were undertaken of response rates and core indicator performance. Country submission rates ranged from 102 (53%) Member States in 2004 to 186 (96%) in 2012. There was great variance in response rates for specific indicators, with the highest response rates for treatment-related indicators. The Global AIDS reporting system has improved substantially over time and has provided key trend data on responses to the HIV epidemic, serving as the global accountability mechanism and providing reference data on the global AIDS response. It will be critical that reporting systems continue to evolve to support the monitoring of the Sustainable Development Goals, in view of ending the AIDS epidemic as a public health threat by 2030.

MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

PubMed Central

Kaunzner, Ulrike W.; Gauthier, Susan A.

2017-01-01

Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression. Clinically, the use of MRI has increased in the past couple decades as a result of improved technology and increased availability that now extends well beyond academic centers. Consequently, there are numerous studies supporting the role of MRI in the management of patients with MS. The aim of this review is to summarize the latest insights into the utility of MRI in MS. PMID:28607577

Building Construction Progress Monitoring Using Unmanned Aerial System (uas), Low-Cost Photogrammetry, and Geographic Information System (gis)

NASA Astrophysics Data System (ADS)

Bognot, J. R.; Candido, C. G.; Blanco, A. C.; Montelibano, J. R. Y.

2018-05-01

Monitoring the progress of building's construction is critical in construction management. However, measuring the building construction's progress are still manual, time consuming, error prone, and impose tedious process of analysis leading to delays, additional costings and effort. The main goal of this research is to develop a methodology for building construction progress monitoring based on 3D as-built model of the building from unmanned aerial system (UAS) images, 4D as-planned model (with construction schedule integrated) and, GIS analysis. Monitoring was done by capturing videos of the building with a camera-equipped UAS. Still images were extracted, filtered, bundle-adjusted, and 3D as-built model was generated using open source photogrammetric software. The as-planned model was generated from digitized CAD drawings using GIS. The 3D as-built model was aligned with the 4D as-planned model of building formed from extrusion of building elements, and integration of the construction's planned schedule. The construction progress is visualized via color-coding the building elements in the 3D model. The developed methodology was conducted and applied from the data obtained from an actual construction site. Accuracy in detecting `built' or `not built' building elements ranges from 82-84 % and precision of 50-72 %. Quantified progress in terms of the number of building elements are 21.31% (November 2016), 26.84 % (January 2017) and 44.19 % (March 2017). The results can be used as an input for progress monitoring performance of construction projects and improving related decision-making process.

Testing the Importance of Individual Growth Curves in Predicting Performance on a High-Stakes Reading Comprehension Test in Florida. Summary. REL 2014-006

ERIC Educational Resources Information Center

Petscher, Yaacov; Kershaw, Sarah; Koon, Sharon; Foorman, Barbara R.

2014-01-01

Districts and schools use progress monitoring to assess student progress, to identify students who fail to respond to intervention, and to further adapt instruction to student needs. Researchers and practitioners often use progress monitoring data to estimate student achievement growth (slope) and evaluate changes in performance over time for…

48 CFR 742.1170 - Performance monitoring and progress reporting.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Performance monitoring and progress reporting. 742.1170 Section 742.1170 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACT MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting...

48 CFR 742.1170 - Performance monitoring and progress reporting.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Performance monitoring and progress reporting. 742.1170 Section 742.1170 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACT MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting...

Tumor necrosis factor alpha inhibitors in the treatment of toxic epidermal necrolysis.

PubMed

Woolridge, Katelyn F; Boler, Patrick L; Lee, Brian D

2018-01-01

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction for which there is no standardized or consistently effective treatment. Due to a greater understanding of disease pathogenesis and the identification of tumor necrosis factor (TNF) α as a mediator of keratinocyte death, TNF-α antagonists have been used in the treatment of TEN. Specifically, infliximab and etanercept have been shown to be effective at halting disease progression. The objective of this study is to review published case reports and case series using anti-TNF-α medications in the treatment of TEN. Results of many of the articles reviewed support the use of TNF-α inhibitors in TEN in both adult and pediatric populations; however, the risks caused by these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

PubMed

Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

2014-09-01

Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity exercised a positive effect in healthy control joints, which increased cartilage sGAG content. More research on this topic might lead to novel insights as to improve cartilage quality. Copyright © 2014 Elsevier Inc. All rights reserved.

A framework for fibromyalgia management for primary care providers.

PubMed

Arnold, Lesley M; Clauw, Daniel J; Dunegan, L Jean; Turk, Dennis C

2012-05-01

Fibromyalgia is a chronic widespread pain disorder commonly associated with comorbid symptoms, including fatigue and nonrestorative sleep. As in the management of other chronic medical disorders, the approach for fibromyalgia management follows core principles of comprehensive assessment, education, goal setting, multimodal treatment including pharmacological (eg, pregabalin, duloxetine, milnacipran) and nonpharmacological therapies (eg, physical activity, behavioral therapy, sleep hygiene, education), and regular education and monitoring of treatment response and progress. Based on these core management principles, this review presents a framework for primary care providers through which they can develop a patient-centered treatment program for patients with fibromyalgia. This proactive and systematic treatment approach encourages ongoing education and patient self-management and is designed for use in the primary care setting. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Clinical monitoring of early caries lesions using cross polarization optical coherence tomography

NASA Astrophysics Data System (ADS)

Fried, Daniel; Staninec, Michal; Darling, Cynthia L.; Chan, Kenneth H.; Pelzner, Roger B.

New methods are needed for the nondestructive measurement of tooth demineralization and remineralization and to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role, since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm. It is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results from two clinical studies underway to measure the effect of fluoride intervention on early lesions. CP-OCT was used to monitor early lesions on enamel and root surfaces before and after intervention with fluoride varnish. The lesion depth and internal structure were resolved for all the lesions examined and some lesions had well defined surface zones of lower reflectivity that may be indicative of arrested lesions. Changes were also noted in the structure of some of the lesions after fluoride intervention.

Development of Less Toxic Treatment Strategies for Metastatic and Drug-Resistant Breast Cancer Using Noninvasive Optical Monitoring

DTIC Science & Technology

2017-09-01

models has been evaluated, with one good option, the Py230 cell lines, as our choice for use in future studies . We have conducted the first study ... Study of Progressive Resistance Major Task 6: dDOS fabrication Subtask 15: Design /Fabricate dDOS system and new custom dDOS probe 6-24 Dr...until year 3 of the study , based on current accrual trends with our clinical collaborators at the Boston Medical Center for different projects, the

Monitoring Indicators of Scholarly Language: A Progress-Monitoring Instrument for Measuring Narrative Discourse Skills

ERIC Educational Resources Information Center

Gillam, Sandra Laing; Gillam, Ronald B.; Fargo, Jamison D.; Olszewski, Abbie; Segura, Hugo

2017-01-01

The purpose of this study was to assess the basic psychometric properties of a progress-monitoring tool designed to measure narrative discourse skills in school-age children with language impairments (LI). A sample of 109 children with LI between the ages of 5 years 7 months and 9 years 9 months completed the "Test of Narrative Language"…

Progress Monitoring in Reading: Comparison of Weekly, Bimonthly, and Monthly Assessments for Students at Risk for Reading Difficulties in Grades 2-4

ERIC Educational Resources Information Center

January, Stacy-Ann A.; Van Norman, Ethan R.; Christ, Theodore J.; Ardoin, Scott P.; Eckert, Tanya L.; White, Mary Jane

2018-01-01

The present study examined the utility of two progress monitoring assessment schedules (bimonthly and monthly) as alternatives to monitoring once weekly with curriculum-based measurement in reading (CBM-R). General education students (N = 93) in Grades 2-4 who were at risk for reading difficulties but not yet receiving special education services…

Oxaliplatin rechallenge in metastatic colorectal cancer patients after prior oxaliplatin treatment.

PubMed

Kim, Jae-Joon; Kang, Jihoon; Hong, Yong Sang; Kim, Kyu-Pyo; Kim, Sun Young; Kim, Tae Won; Kim, Jeong Eun

2018-04-05

Because the number of cytotoxic agents available for the treatment of metastatic colorectal cancer (mCRC) is limited, rechallenge with the same chemotherapy agents can provide a continuum of treatment. This study investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC patients who had been previously exposed to oxaliplatin-based chemotherapy. Patients were included if they had mCRC and evaluable disease, had remained disease-free or progression-free for at least 6 months after the last dose of prior oxaliplatin-based therapy, and were retreated with oxaliplatin therapy. Between January 2009 and May 2014, 110 patients were retreated with oxaliplatin-based regimens; of these, 42 (38.2%) had received prior oxaliplatin as adjuvant chemotherapy and 68 (61.8%) as palliative chemotherapy. The overall response rate to oxaliplatin rechallenge was 30.9% (34/110), and the disease control rate was 68.2% (75/110), with one patient achieving complete response, 33 achieving partial response, and 41 having stable disease. Median progression-free survival and overall survival following oxaliplatin rechallenge were 5.9 months (95% confidence interval [CI], 4.4-7.4 months) and 18.5 months (95% CI, 14.0-23.0 months), respectively. Sixteen patients experienced grade 2 or 3 neuropathy. Ten patients experienced any grade hypersensitivity reaction within four cycles of treatment, including six who stopped treatment due to grade 3 or 4 hypersensitivity reactions. Rechallenge with oxaliplatin-based therapy may be an option for patients who achieve at least 6 months of disease-free or progression-free survival with prior oxaliplatin-based chemotherapy. However, neurotoxicity and hypersensitivity reactions should be carefully monitored in this setting.

Monitoring tooth demineralization using a cross polarization optical coherence tomographic system with an integrated MEMS scanner

NASA Astrophysics Data System (ADS)

Fried, Daniel; Staninec, Michal; Darling, Cynthia; Kang, Hobin; Chan, Kenneth

2012-01-01

New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm, it is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results using a new cross-polarization OCT system introduced by Santec. This system utilizes a swept laser source and a MEMS scanner for rapid acquisition of cross polarization images. Preliminary studies show that this system is useful for measurement of the severity of demineralization on tooth surfaces and for showing the spread of occlusal lesions under the dentinal-enamel junction.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

PubMed

Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert

2016-12-12

Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm 3 ). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm 3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Hydraulic fracture monitoring in hard rock at 410 m depth with an advanced fluid-injection protocol and extensive sensor array

NASA Astrophysics Data System (ADS)

Zang, Arno; Stephansson, Ove; Stenberg, Leif; Plenkers, Katrin; Specht, Sebastian; Milkereit, Claus; Schill, Eva; Kwiatek, Grzegorz; Dresen, Georg; Zimmermann, Günter; Dahm, Torsten; Weber, Michael

2017-02-01

In this paper, an underground experiment at the Äspö Hard Rock Laboratory (HRL) is described. Main goal is optimizing geothermal heat exchange in crystalline rock mass at depth by multistage hydraulic fracturing with minimal impact on the environment, that is, seismic events. For this, three arrays with acoustic emission, microseismicity and electromagnetic sensors are installed mapping hydraulic fracture initiation and growth. Fractures are driven by three different water injection schemes (continuous, progressive and pulse pressurization). After a brief review of hydraulic fracture operations in crystalline rock mass at mine scale, the site geology and the stress conditions at Äspö HRL are described. Then, the continuous, single-flow rate and alternative, multiple-flow rate fracture breakdown tests in a horizontal borehole at depth level 410 m are described together with the monitoring networks and sensitivity. Monitoring results include the primary catalogue of acoustic emission hypocentres obtained from four hydraulic fractures with the in situ trigger and localizing network. The continuous versus alternative water injection schemes are discussed in terms of the fracture breakdown pressure, the fracture pattern from impression packer result and the monitoring at the arrays. An example of multistage hydraulic fracturing with several phases of opening and closing of fracture walls is evaluated using data from acoustic emissions, seismic broad-band recordings and electromagnetic signal response. Based on our limited amount of in situ tests (six) and evaluation of three tests in Ävrö granodiorite, in the multiple-flow rate test with progressively increasing target pressure, the acoustic emission activity starts at a later stage in the fracturing process compared to the conventional fracturing case with continuous water injection. In tendency, also the total number and magnitude of acoustic events are found to be smaller in the progressive treatment with frequent phases of depressurization.

Wireless patient monitoring on shoe for the assessment of foot dysfunction: an overview

NASA Astrophysics Data System (ADS)

Abraham, Jose K.; Whitchurch, Ashwin K.; Varadan, Vijay K.; Sarukesi, Karunakaran

2003-04-01

This paper presents an overview of the wireless monitoring and quantitative assessment of joint dynamics of ankle which has suffered from soft tissue injury, immobilization or any dysfunction with special focus on the treatment and rehabilitation applications. The inadequacy of a reliable and easy method for continuous measurement and recording of ankle movement while doing physical therapy makes the monitoring of its progress difficult. Development of a wireless ankle motion monitoring system inside the shoe provides information on several aspects of activities associated with a dysfunctional foot. The system is based on continuous wireless monitoring of signals from accelerometers and gyroscopes fixed inside the shoe. From these signals, the duration, rate, and moment of occurrence of activities associated with mobility (e.g., lying, sitting, standing, walking up and down, running, cycling, wheelchair use and general movement) and transitions (changes in angle) can be detected. Information about the movement can be obtained by the acceleration sensors, which is related to the intensity of body-segment movement. Apart from monitoring accelerations, other signals due to turning and angular movements can be obtained using the miniature gyroscope attached to the shoe.

Fabry nephropathy: a review - how can we optimize the management of Fabry nephropathy?

PubMed

Waldek, Stephen; Feriozzi, Sandro

2014-05-06

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment.

Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy.

PubMed

Nascimento Osorio, A; Medina Cantillo, J; Camacho Salas, A; Madruga Garrido, M; Vilchez Padilla, J J

2018-03-09

Duchenne muscular dystrophy (DMD) is the most common myopathy in children, with a worldwide prevalence of approximately 0.5 cases per 10,000 male births. It is characterised by a progressive muscular weakness manifesting in early childhood, with the subsequent appearance of musculoskeletal, respiratory, and cardiac complications, causing disability, dependence, and premature death. Currently, DMD is mainly managed with multidisciplinary symptomatic treatment, with favourable results in terms of the progression of the disease. It is therefore crucial to establish clear, up-to-date guidelines enabling early detection, appropriate treatment, and monitoring of possible complications. We performed a literature search of the main biomedical databases for articles published in the last 10years in order to obtain an overview of the issues addressed by current guidelines and to identify relevant issues for which no consensus has yet been established. The degree of evidence and level of recommendation of the information obtained were classified and ordered according to the criteria of the American Academy of Neurology. DMD management should be multidisciplinary and adapted to the patient's profile and the stage of clinical progression. In addition to corticotherapy, treatment targeting gastrointestinal, respiratory, cardiac, and orthopaedic problems, as well as physiotherapy, should be provided with a view to improving patients' quality of life. Genetic studies play a key role in the management of the disease, both in detecting cases and potential carriers and in characterising the mutation involved and developing new therapies. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

PubMed Central

2014-01-01

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

PubMed

Fernández, Oscar; Izquierdo, Guillermo; Fernández, Victoria; Leyva, Laura; Reyes, Virginia; Guerrero, Miguel; León, Antonio; Arnaiz, Carlos; Navarro, Guillermo; Páramo, Maria Dolores; Cuesta, Antonio De la; Soria, Bernat; Hmadcha, Abdelkrim; Pozo, David; Fernandez-Montesinos, Rafael; Leal, Maria; Ochotorena, Itziar; Gálvez, Patricia; Geniz, Maria Angeles; Barón, Francisco Javier; Mata, Rosario; Medina, Cristina; Caparrós-Escudero, Carlos; Cardesa, Ana; Cuende, Natividad

2018-01-01

Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Metabolomic signatures of chronic kidney disease of diverse etiologies in the rats and humans

DOE PAGES

Zhang, Zhi -Hao; Chen, Hua; Vaziri, Nosratola D.; ...

2016-09-16

Chronic kidney disease (CKD) has emerged as a major public health problem worldwide. It frequently progresses to end-stage renal disease, which is related to very high cost and mortality. Novel biomarkers can provide insight into the novel mechanism, facilitate early detection, and monitor progression of CKD and its response to therapeutic interventions. To identify potential biomarkers, we applied an UPLC-HDMS together with univariate and multivariate statistical analyses using plasma samples from patients with CKD of diverse etiologies (100 sera in discovery set and 120 sera in validation set) and two different rat models of CKD. Using comprehensive screening and validationmore » workflow, we identified a panel of seven metabolites that were shared by all patients and animals regardless of the underlying cause of CKD. These included ricinoleic acid, stearic acid, cytosine, LPA(16:0), LPA(18:2), 3-methylhistidine, and argininic acid. The combination of these seven biomarkers enabled the discrimination of patients with CKD from healthy subjects with a sensitivity of 83.3% and a specificity of 96.7%. In addition, these biomarkers accurately reflected improvements in renal function in response to the therapeutic interventions. Lastly, our results indicated that the identified biomarkers may improve the diagnosis of CKD and provide a novel tool for monitoring of the progression of disease and response to treatment in CKD patients.« less

Metabolomic signatures of chronic kidney disease of diverse etiologies in the rats and humans

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

Zhang, Zhi -Hao; Chen, Hua; Vaziri, Nosratola D.

Chronic kidney disease (CKD) has emerged as a major public health problem worldwide. It frequently progresses to end-stage renal disease, which is related to very high cost and mortality. Novel biomarkers can provide insight into the novel mechanism, facilitate early detection, and monitor progression of CKD and its response to therapeutic interventions. To identify potential biomarkers, we applied an UPLC-HDMS together with univariate and multivariate statistical analyses using plasma samples from patients with CKD of diverse etiologies (100 sera in discovery set and 120 sera in validation set) and two different rat models of CKD. Using comprehensive screening and validationmore » workflow, we identified a panel of seven metabolites that were shared by all patients and animals regardless of the underlying cause of CKD. These included ricinoleic acid, stearic acid, cytosine, LPA(16:0), LPA(18:2), 3-methylhistidine, and argininic acid. The combination of these seven biomarkers enabled the discrimination of patients with CKD from healthy subjects with a sensitivity of 83.3% and a specificity of 96.7%. In addition, these biomarkers accurately reflected improvements in renal function in response to the therapeutic interventions. Lastly, our results indicated that the identified biomarkers may improve the diagnosis of CKD and provide a novel tool for monitoring of the progression of disease and response to treatment in CKD patients.« less

Early detection of health and welfare compromises through automated detection of behavioural changes in pigs.

PubMed

Matthews, Stephen G; Miller, Amy L; Clapp, James; Plötz, Thomas; Kyriazakis, Ilias

2016-11-01

Early detection of health and welfare compromises in commercial piggeries is essential for timely intervention to enhance treatment success, reduce impact on welfare, and promote sustainable pig production. Behavioural changes that precede or accompany subclinical and clinical signs may have diagnostic value. Often referred to as sickness behaviour, this encompasses changes in feeding, drinking, and elimination behaviours, social behaviours, and locomotion and posture. Such subtle changes in behaviour are not easy to quantify and require lengthy observation input by staff, which is impractical on a commercial scale. Automated early-warning systems may provide an alternative by objectively measuring behaviour with sensors to automatically monitor and detect behavioural changes. This paper aims to: (1) review the quantifiable changes in behaviours with potential diagnostic value; (2) subsequently identify available sensors for measuring behaviours; and (3) describe the progress towards automating monitoring and detection, which may allow such behavioural changes to be captured, measured, and interpreted and thus lead to automation in commercial, housed piggeries. Multiple sensor modalities are available for automatic measurement and monitoring of behaviour, which require humans to actively identify behavioural changes. This has been demonstrated for the detection of small deviations in diurnal drinking, deviations in feeding behaviour, monitoring coughs and vocalisation, and monitoring thermal comfort, but not social behaviour. However, current progress is in the early stages of developing fully automated detection systems that do not require humans to identify behavioural changes; e.g., through automated alerts sent to mobile phones. Challenges for achieving automation are multifaceted and trade-offs are considered between health, welfare, and costs, between analysis of individuals and groups, and between generic and compromise-specific behaviours. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Efficacy and Safety of Ruxolitinib in the Treatment of Patients with Myelofibrosis

PubMed Central

Yi, Cecilia Arana; Tam, Constantine S.; Verstovsek, Srdan

2016-01-01

The JAK 1 and JAK2 inhibitor ruxolitinib has approved indications in myelofibrosis, a BCR-ABL1-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis and shortened survival. In Phase III clinical studies, ruxolitinib provided rapid and durable improvement of myelofibrosis-related splenomegaly and symptoms irrespective of mutation status, and was associated with a survival advantage compared with placebo or best available therapy. Because of dose-dependent cytopenias, blood count monitoring and dose titration are important to optimize therapy. Specific precautions apply to the treatment of patients with or at risk of serious infections. Discontinuation of ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is approved for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. PMID:25757677

ADVANTAGES OF REMOTE MONITORING THE ACTIVITY OF PATIENTS WITH AXIAL SPONDYLITIS (PROGRESS STUDY).

PubMed

Gaidukova, I Z; Akulova, A I; Aparkina, A V; Rebrov, A P

To improve the quality of treatment of patients with spondyloarthrities based on analysis of adherence to therapy and its timely correction by regular remote monitoring the activity of the disease. 46 patents with axial spondylitis (ankylosing spondylitis, non-radiographic spondylitis) were interviewed by phone once in 4 weeks for 18 months with a 3 month interval after 12 months. 96 patients underwent routine outpatient examination for the evaluation of the main parameters of the disease. Arbitrarily examined patients with spondyloarthritis reported poor compliance with therapy and its low efficiency. During 18 months, 79% of the patients were recommended treatment with TNF-a inhibitors. Only 18.5% of them in the remote monitoring group failed to reach the BASDAI index S 4 whereas 73.9% of the patients examined remotely for 1 year had low activity of the disease or its partial remission. An increased period between two phone interviews from 1 to 3 months in 58.6% patients with low activity of the disease was associated with impaired adherence to therapy (decreased intake of the anti-inflammatory drug or its withdrawal) that did not lead to enhancement of activity during 3 months after the change in the treatment. Remote monitoring of activity of the disease (one phone interview every 4 weeks) allows to decrease it or reach remission in 73.9% of the patients with axial spondyloarthritis. The decrease in the frequency of telephone calls to one every 3 months results in the impairment of compliance with therapy but does not lead to increase of disease activity in the short run.

Update on lysosomal acid lipase deficiency: Diagnosis, treatment and patient management.

PubMed

Camarena, Carmen; Aldamiz-Echevarria, Luis J; Polo, Begoña; Barba Romero, Miguel A; García, Inmaculada; Cebolla, Jorge J; Ros, Emilio

2017-05-10

Lysosomal acid lipase deficiency (LALD) is an ultra-rare disease caused by a congenital disorder of the lipid metabolism, characterized by the deposition of cholesterol esters and triglycerides in the organism. In patients with no enzyme function, the disease develops during the perinatal period and is invariably associated with death during the first year of life. In all other cases, the phenotype is heterogeneous, although most patients develop chronic liver diseases and may also develop an early cardiovascular disease. Treatment for LALD has classically included the use of supportive measures that do not prevent the progression of the disease. In 2015, regulatory agencies approved the use of a human recombinant LAL for the treatment of LALD. This long-term enzyme replacement therapy has been associated with significant improvements in the hepatic and lipid profiles of patients with LALD, increasing survival rates in infants with a rapidly progressive disease. Both the severity of LALD and the availability of a specific treatment highlight the need to identify these patients in clinical settings, although its low prevalence and the existing clinical overlap with other more frequent pathologies limit its diagnosis. In this paper we set out practical recommendations to identify and monitor patients with LALD, including a diagnostic algorithm, along with an updated treatment. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Efficacy of plasma vascular endothelial growth factor in monitoring first-line chemotherapy in patients with advanced non-small cell lung cancer

PubMed Central

2009-01-01

Background Along with the development of new cancer therapeutics, more effective tools for the estimation of response to therapy and prediction of disease progression are required for the better management of inoperable cancer patients. Methods We studied 134 newly diagnosed and primarily untreated advanced non-small cell lung cancer patients and 100 controls. Forty two patients received platinum-based chemotherapy. Plasma VEGF levels were quantified in all samples at baseline and also before second and third chemotherapy cycle in 42 patients and correlated with response to therapy as assessed by computed tomography after the third chemotherapy cycle. Results We observed that, patients who went into remission had significantly lower baseline VEGF levels before second and third cycles of chemotherapy when compared with patients with no change and progression. Plasma VEGF levels showed a greater decrease from cycle 1 to 2 and from cycle 1 to 3 in patients who showed remission in comparison to those with no change or progression. Plasma VEGF levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 76.9% and 75.0%, respectively (area under the ROC curve = 0.724). Early prediction of disease progression was achieved with a sensitivity and specificity of 71.4% for plasma VEGF before cycle 2 (area under the ROC curve = 0.805). The kinetics of VEGF form cycle 1 to 2 and cycle 1 to 3 also gave significant information for predicting disease progression as well as insufficient therapy response. Conclusion Monitoring of plasma VEGF levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This may help in individualizing treatment and could lead to better management of the advanced stage lung cancer. PMID:19958548

Multidisciplinary therapy for the treatment of malocclusion in a patient with chronic periodontitis with a five-year follow-up: A case report.

PubMed

Zhang, Dongmei; Lin, Li; Tang, Xiaoling; Li, Chen; Liu, Jingbo; Wang, Hongyang; Pan, Yaping

2017-10-01

Multidisciplinary therapy is essential in dental practice to achieve optimized outcomes. The present case report describes the application of periodontal surgery with a five-year follow-up in a patient with malocclusion and chronic periodontitis. In the presence of periodontal inflammation, orthodontic therapy may result in further periodontal breakdown due to plaque accumulation. In order to prevent this progression, scaling and root planning with a periodontal endoscope was applied, and continuous clinical monitoring and risk assessment was performed every 3 months using a Florida Probe. This combined treatment supports the long-term maintenance of periodontal conditions, functional occlusion and harmony of the facial profile.

Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

PubMed

Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E

2016-12-01

No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.

Gene Therapy Using Therapeutic and Diagnostic Recombinant Oncolytic Vaccinia Virus GLV-1h153 for Management of Colorectal Peritoneal Carcinomatosis

PubMed Central

Eveno, Clarisse; Mojica, Kelly; Ady, Justin W.; Thorek, Daniel L.J.; Longo, Valerie; Belin, Laurence J.; Gholami, Sepideh; Johnsen, Clark; Zanzonico, Pat; Chen, Nanhai; Yu, Tony; Szalay, Aladar A.; Fong, Yuman

2015-01-01

Background Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC). Poor response to cytoreductive surgery and chemotherapy, coupled with the inability to reliably track disease progression using established diagnostic methods make this a deadly disease. This paper examines the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression of the human sodium iodide transporter (hNIS) can provide both real-time monitoring of viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC). Methods Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in-vitro. Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts were generated in athymic nude mice, and subsequently administered GLV-1h153 intraperitoneally. Reduction of tumor burden was assessed by mass. Orthotopic tumors were visualized by SPECT/CT after Iodine (131I) administration and by fluorescence optical imaging. Results GLV-1h153 infected and killed CRC cells in a time and concentration dependent manner. Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a significant reduction of tumor burden. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusions GLV-1h153 effectively kills CRC in-vitro and dramatically reduces tumor burden in-vivo. We demonstrate that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden in-vivo. These findings indicate that GLV-1h153 has significant potential for use as theragnostic agent in the treatment of CRPC. PMID:25616946

mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group

PubMed Central

Rodríguez, Marta; Cantos, Blanca; Sabín, Pilar; Quero, Cristina; García-Arroyo, Francisco R.; Rueda, Antonio; Maximiano, Constanza; Rodríguez-Abreu, Delvys; Sánchez, Antonio; Silva, Javier

2017-01-01

Purpose To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Patients and Methods Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. Results In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. Conclusions This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapy. PMID:28881619

mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group.

PubMed

Provencio, Mariano; Rodríguez, Marta; Cantos, Blanca; Sabín, Pilar; Quero, Cristina; García-Arroyo, Francisco R; Rueda, Antonio; Maximiano, Constanza; Rodríguez-Abreu, Delvys; Sánchez, Antonio; Silva, Javier; García, Vanesa

2017-08-01

To determine the feasibility of mRNAs ( C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT ) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapy.

Biological markers of melancholia and reclassification of depressive disorders.

PubMed

Greden, J F

1982-01-01

Pathophysiological markers of melancholia are being developed in four major areas: 1) neuroendocrine; 2) sleep; 3) psychomotor and 4) biochemical. Neuroendocrine markers include a failure of suppress plasma cortisol secretion in the dexamethasone suppression test (DST), diminished thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH stimulation test), and blunted growth hormone response to a variety of stimulating agents such as d-amphetamine, methylamphetamine, clonidine, L-dopa and insulin (growth hormone test). Of these, the DST is the best standardized. It is a highly specific laboratory marker with documented value in diagnosis, assessing prognosis and monitoring treatment progress. Sleep EEG abnormalities include reduced REM latency, increased REM density, reduction in delta sleep and impaired sleep efficiency. Sleep EEGs are pragmatically difficult, but results are quite specific. Elongated speech pause time (SPT) during "automatic speech" is a promising marker of psychomotor regulation. This simple, non-invasive measure may have special value in reducing clinical subjectivity and in monitoring treatment progress. Biochemical markers include: 1) platelet monoamine oxidase (MAO) activity; 2) in vitro lithium RBC transport and 3) urinary MHPG levels. Standardizations of biochemical tests are still lacking. Most biological tests for melancholia operate by indirectly "marking" CNS limbic system dysfunction. For wide acceptance, a test must be safe, moderately sensitive, highly specific, practical, relatively inexpensive and not significantly altered by common anti-depressant treatments. The DST best meets these criteria at this time. Proper utilization of test results requires knowledge of baseline prevalence rates and of the concepts of sensitivity (true-positive rate), specificity (true negative rate) and positive and negative predictive values (diagnostic confidence). No single marker will meet all clinical needs. Combinations or serial use of tests will hopefully enhance their already considerable usefulness.

Monticello Mill Tailings Site Operable Unit III Annual Groundwater Report May 2014 Through April 2015, October 2015

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

Nguyen, Jason; Smith, Fred

This report provides the annual analysis of water quality restoration progress, cumulative through April 2015, for Operable Unit (OU) III, surface water and groundwater, of the U.S. Department of Energy (DOE) Office of Legacy Management Monticello Mill Tailings Site (MMTS). The MMTS is a Comprehensive Environmental Response, Compensation, and Liability Act National Priorities List site located in and near the city of Monticello, San Juan County, Utah. MMTS comprises the 110-acre site of a former uranium- and vanadium-ore-processing mill (mill site) and 1,700 acres of surrounding private and municipal property. Milling operations generated 2.5 million cubic yards of waste (tailings)more » from 1942 to 1960. The tailings were impounded at four locations on the mill site. Inorganic constituents in the tailings drained from the impoundments to contaminate local surface water (Montezuma Creek) and groundwater in the underlying alluvial aquifer. Mill tailings dispersed by wind and water also contaminated properties surrounding and downstream of the mill site. Remedial actions to remove and isolate radiologically contaminated soil, sediment, and debris from the former mill site (OU I) and surrounding properties (OU II) were completed in 1999 with the encapsulation of the wastes in an engineered repository located on DOE property 1 mile south of the former mill site. Contamination of groundwater and surface water remains within OU III at levels that exceed water quality protection standards. Uranium is the primary contaminant of concern. LM implemented monitored natural attenuation with institutional controls as the OU III remedy in 2004. Because groundwater restoration proceeded more slowly than expected and did not meet performance criteria established in the OU III Record of Decision (June 2004), LM implemented a contingency action in 2009 by an Explanation of Significant Difference to include a pump-and-treat system using a single extraction well and treatment by zero-valent iron (ex-situ treatment system). The contingency action was optimized in 2015 with the installation of 8 extraction wells and 16 monitoring wells in a focused area of the aquifer (area of attainment). Contaminated water is treated by solar evaporation at an existing onsite LM facility. Environmental monitoring at OU III consists of twice-yearly (April and October) collection and analysis of hydrologic and water-quality data from an established network of observation wells, seeps, and surface water locations. The scope of monitoring was expanded in 2009 for the ex situ treatment system and in 2015 for the remedy optimization system. Operation and monitoring of the ex situ treatment system was discontinued in 2014 with the start-up of the remedy optimization system. No data anomalies for OU III water quality trending or restoration progress are identified for the May 2014 through April 2015 reporting period. Although some regions of the aquifer demonstrate decreasing concentration trends, such trending is not evident for the bulk of the aquifer and a prolonged restoration period is indicated. The groundwater contingency remedy optimization system captures significant contaminant mass (primarily uranium) from the area of attainment; however, because that system only became operational in 2015, a long-term forecast of restoration progress is premature.« less

Real-time optoacoustic monitoring of stroke

NASA Astrophysics Data System (ADS)

Kneipp, Moritz; Turner, Jake; Hambauer, Sebastian; Krieg, Sandro M.; Lehmberg, Jens; Lindauer, Ute; Razansky, Daniel

2014-03-01

Characterizing disease progression and identifying possible therapeutic interventions in stroke is greatly aided by the use of longitudinal function imaging studies. In this study, we investigate the applicability of real-time multispectral optoacoustic tomography (MSOT) as a tool for non-invasive monitoring of the progression of stroke in the whole brain. The middle cerebral artery occlusion (MCAO) method was used to induce stroke. Mice were imaged under isoflurane anesthesia preoperatively and at several time points during and after the 60-minute occlusion. The animals were sacrificed after 24 hours and their excised brains frozen at -80°C for sectioning. The cryosection were stained using H&E staining to identify the ischemic lesion. Major vessels are readily identifiable in the whole mouse head in the in vivo optoacoustic scans. During ischemia, a reduction in cerebral blood volume is detectable in the cortex. Post ischemia, spectral unmixing of the optoacoustic signals shows an asymmetry of the deoxygenated hemoglobin in the hemisphere affected by MCAO. This hypoxic area was mainly located around the boundary of the ischemic lesion and was therefore identified as the ischemic penumbra. Non-invasive functional MSOT imaging is able to visualize the hypoxic penumbra in brains affected by stroke. Stopping the spread of the infarct area and revitalizing the penumbra is central in stroke research, this new imaging technique may therefore prove to be a valuable tool in the monitoring and developing new treatments.

Type I Diabetic Akita Mouse Model is Characterized by Abnormal Cardiac Deformation During Early Stages of Diabetic Cardiomyopathy with Speckle-Tracking Based Strain Imaging.

PubMed

Zhou, Yingchao; Xiao, Hong; Wu, Jianfei; Zha, Lingfeng; Zhou, Mengchen; Li, Qianqian; Wang, Mengru; Shi, Shumei; Li, Yanze; Lyu, Liangkun; Wang, Qing; Tu, Xin; Lu, Qiulun

2018-01-01

Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

Monitoring Students' Academic & Disciplinary Progression.

ERIC Educational Resources Information Center

McDonald, Fred; Kellogg, Larry J.

This document outlines the objectives and procedures of a program at a New Mexico school district whose purpose is to enable school personnel to systematically monitor students' academic and disciplinary progression. The objectives of the program are to diagnose academic or disciplinary problems and prescribe remedies, to establish an oncampus…

Safe Gene Therapy for Type 1 Diabetes

DTIC Science & Technology

2011-10-01

together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability...together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability of...10. In addition, we will continue to investigate their potential therapeutic function in halting the progression of islet-autoimmunity in prediabetic

Idelalisib for the treatment of non-Hodgkin lymphoma

PubMed Central

Gopal, Ajay; Graf, Solomon

2016-01-01

Introduction B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia. Areas Covered Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies. Expert Opinion Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations. PMID:26818003

Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies

PubMed Central

Arvanitidis, A.; Henriksen, K.; Karsdal, M.A.; Nedergaard, A.

2016-01-01

For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor biomarkers that can predict the disease progression would be an important advancement. Most muscle diseases involve accelerated muscle fiber degradation, inflammation, fatty tissue substitution and/or fibrosis. All these pathological traits have been shown to give rise to serological peptide biomarkers in other tissues, underlining the potential application of existing biomarkers of such traits in muscle disorders. A significant quantity of tissue is involved in these pathological mechanisms alongside with qualitative changes in protein turnover in myofibrillar, extra-cellular matrix and immunological cell protein fractions accompanied by alterations in body fluids. We propose that protein and peptides can leak out of the afflicted muscles and can be of use in diagnosis, prediction of pathology trajectory and treatment efficacy. Proteolytic cleavage systems are especially modulated during a range of muscle pathologies, thereby giving rise to peptides that are differentially released during disease manifestation. Therefore, we believe that pathology-specific post-translational modifications like cleavages can give rise to neoepitope peptides that may represent a promising class of peptides for discovery of biomarkers pertaining to neuromuscular diseases. PMID:27854226

Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial

PubMed Central

Hu, Kun; Riemersma - van der Lek, Rixt F.; Patxot, Melissa; Li, Peng; Shea, Steven A.; Scheer, Frank A. J. L.; Van Someren, Eus J. W.

2016-01-01

Cross-sectional studies show that activity fluctuations in healthy young adults possess robust temporal correlations that become altered with aging, and in dementia and depression. This study was designed to test whether or not within-subject changes of activity correlations (i) track the clinical progression of dementia, (ii) reflect the alterations of depression symptoms in patients with dementia, and (iii) can be manipulated by clinical interventions aimed at stabilizing circadian rhythmicity and improving sleep in dementia, namely timed bright light therapy and melatonin supplementation. We examined 144 patients with dementia (70–96 years old) who were assigned to daily treatment with bright light, bedtime melatonin, both or placebos only in a 3.5-year double-blinded randomized clinical trial. We found that activity correlations at temporal scales <~2 hours significantly decreased over time and that light treatment attenuated the decrease by ~73%. Moreover, the decrease of temporal activity correlations positively correlated with the degrees of cognitive decline and worsening of mood though the associations were relatively weak. These results suggest a mechanistic link between multiscale activity regulation and circadian/sleep function in dementia patients. Whether temporal activity patterns allow unobtrusive, long-term monitoring of dementia progression and mood changes is worth further investigation. PMID:27292543

Long Term Results of Visual Field Progression Analysis in Open Angle Glaucoma Patients Under Treatment.

PubMed

Kocatürk, Tolga; Bekmez, Sinan; Katrancı, Merve; Çakmak, Harun; Dayanır, Volkan

2015-01-01

To evaluate visual field progression with trend and event analysis in open angle glaucoma patients under treatment. Fifteen year follow-up results of 408 eyes of 217 glaucoma patients who were followed at Adnan Menderes University, Department of Ophthalmology between 1998 and 2013 were analyzed retrospectively. Visual field data were collected for Mean Deviation (MD), Visual Field Index (VFI), and event occurrence. There were 146 primary open-angle glaucoma (POAG), 123 pseudoexfoliative glaucoma (XFG) and 139 normal tension glaucoma (NTG) eyes. MD showed significant change in all diagnostic groups (p<0.001). The difference of VFI between first and last examinations were significantly different in POAG (p<0.001), and XFG (p<0.003) but not in NTG. VFI progression rates were -0.3, -0.43, and -0.2 % loss/year in treated POAG, XFG, and NTG, respectively. The number of empty triangles were statistically different between POAG-NTG (p=0.001), and XFG-NTG (p=0.002) groups. The number of half-filled (p=0.002), and full-filled (p=0.010) triangles were significantly different between XFG-NTG groups. Functional long-term follow-up of glaucoma patients can be monitored with visual field indices. We herein report our fifteen year follow-up results in open angle glaucoma.

Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review.

PubMed

Eriksen, Erik F; Díez-Pérez, Adolfo; Boonen, Steven

2014-01-01

Osteoporosis is a progressive skeletal disorder that requires long-term treatment. However, there is little guidance regarding optimal treatment duration and what the treatment discontinuation and retreatment criteria should be. Given that bisphosphonates are the most commonly prescribed class of agent for the treatment of osteoporosis, we reviewed the long-term data relating to these therapies and discussed the considerations for using bisphosphonates in postmenopausal women with osteoporosis. A PubMed search, using the search terms 'bisphosphonate', 'postmenopausal osteoporosis' and 'long term' and/or 'extension' was conducted in January 2013. Results from nine controlled studies that prospectively assessed alendronate, risedronate, ibandronate or zoledronic acid in women with postmenopausal osteoporosis were reviewed. Clinical studies in postmenopausal women with osteoporosis showed that long-term use of bisphosphonates resulted in persistent antifracture and bone mineral density (BMD) increasing effects beyond 3 years of treatment. No unexpected adverse events were identified in these studies and the long-term tolerability profiles of bisphosphonates remain favorable. Data from the withdrawal extension studies of alendronate and zoledronic acid also showed that residual fracture benefits were seen in patients who discontinued treatment for 3 to 5 years after an initial 3- to 5-year treatment period. BMD monitoring and fracture risk assessments should be conducted regularly to determine whether treatment could be stopped or should be reinitiated. Patients exhibiting T-scores<-2.5 or who have suffered a new fracture while on treatment should continue treatment, while patients with T-scores>-2.5 could be considered for discontinuation of active treatment while undergoing continued monitoring of their bone health. The duration and potential discontinuation of treatment should be personalized for individual patients based on their response to treatment, fracture risk and comorbidities. © 2013. Published by Elsevier Inc. All rights reserved.

Infantile developmental thoracolumbar kyphosis with segmental subluxation of the spine: report of five patients and review of the literature.

PubMed

Ganesan, S; Karampalis, C; Garrido, E; Tsirikos, A I

2015-07-01

Acute angulation at the thoracolumbar junction with segmental subluxation of the spine occurring at the level above an anteriorly hypoplastic vertebra in otherwise normal children is a rare condition described as infantile developmental thoracolumbar kyphosis. Three patient series with total of 18 children have been reported in the literature. We report five children who presented with thoracolumbar kyphosis and discuss the treatment algorithm. We reviewed the medical records and spinal imaging at initial clinical presentation and at minimum two-year follow-up. The mean age at presentation was eight months (two to 12). All five children had L2 anterior vertebral body hypoplasia. The kyphosis improved spontaneously in three children kept under monitoring. In contrast, the deformity was progressive in two patients who were treated with bracing. The kyphosis and segmental subluxation corrected at latest follow-up (mean age 52 months; 48 to 60) in all patients with near complete reconstitution of the anomalous vertebra. The deformity and radiological imaging on a young child can cause anxiety to both parents and treating physicians. Diagnostic workup and treatment algorithm in the management of infantile developmental thoracolumbar kyphosis is proposed. Observation is indicated for non-progressive kyphosis and bracing if there is evidence of kyphosis and segmental subluxation deterioration beyond walking age. Surgical stabilisation of the spine can be reserved for severe progressive deformities unresponsive to conservative treatment. ©2015 The British Editorial Society of Bone & Joint Surgery.

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression.

PubMed

Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E; Joshi, Virendra; Salomon, Carlos

2017-03-07

Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a 'fingerprint' of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

Feasibility of portable sleep monitors to detect obstructive sleep apnea (OSA) in a vulnerable urban population.

PubMed

Nickerson, Jillian; Lee, Euny; Nedelman, Michael; Aurora, R Nisha; Krieger, Ana; Horowitz, Carol R

2015-01-01

Portable sleep monitors may offer a convenient method to expand detection of obstructive sleep apnea (OSA), yet few studies have evaluated this technology in vulnerable populations. We therefore aimed to assess the feasibility and acceptability of portable sleep monitors for detection of OSA in a prediabetic, urban minority population. We recruited a convenience sample of participants at their 12-month follow-up for a community-partnered, peer-led lifestyle intervention aimed to prevent diabetes in prediabetic and overweight patients in this prospective mixed-methods pilot study. All participants wore portable sleep monitors overnight at home. We qualitatively explored perceptions about OSA and portable monitors in a subset of participants. We tested 72 people, predominantly non-White, female, Spanish speaking, uninsured, and of low income. Use of portable sleep monitors was feasible: 100% of the monitors were returned and all participants received results. We detected OSA in 49% (defined as an Apnea-Hypopnea Index [AHI] >5) and moderate-severe OSA in 14% (AHI >15) requiring treatment in 14%. In 21 qualitative interviews, participants supported increased use of portable sleep monitors in their community, were appropriately concerned that OSA could cause progression to diabetes, and thought weight loss could prevent or improve OSA. Portable sleep monitors may represent a feasible method for detecting OSA in high-risk urban minority populations. © Copyright 2015 by the American Board of Family Medicine.

Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

Changes in the frequency of food intake among children and teenagers: monitoring in a reference service.

PubMed

Mariz, Larissa Soares; Medeiros, Carla Campos Muniz; Vieira, Caroline Evelin Nascimento Kluczynik; Enders, Bertha Cruz; Coura, Alexsandro Silva

2013-01-01

to identify changes in the food intake patterns among overweight children and teenagers, treated at a reference medical centre. the method used is that of a cohort study, between April 2010 and April 2011. A total of 109 children and teenagers, either obese or overweight, took part in the study. The population was divided into two subgroups depending on the permanence period (more than 6 months, and less than 6 months off the treatment). The chi-square test and logistic regression were carried out. the group which had been longer off the treatment tended to consume more soft drinks, pasta and fried foods, and less fruit and vegetables. The group with less time showed an improvement, with a reduction of consumption of soft drinks and other goodies. There was confirmation of an increased risk for consumption of soft drinks, pasta and goodies in general, as also detachment from the treatment in adolescence. The group with a longer period of monitoring has had a positive change in food intake frequency. The main contribution made by this study is that of showing that multiprofessional treatment, including some nursing care, is efficient in progressively changing the food intake of children and adolescents who are overweight.

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

PubMed Central

Otin, Sofia; Fuertes, Maria I.; Vilades, Elisa; Gracia, Hector; Ara, Jose R.; Alarcia, Raquel; Polo, Vicente; Larrosa, Jose M.; Pablo, Luis E.

2016-01-01

Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer's disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression. PMID:27840739

SPIRIT: A seamless phase I/II randomized design for immunotherapy trials.

PubMed

Guo, Beibei; Li, Daniel; Yuan, Ying

2018-06-07

Immunotherapy-treatments that enlist the immune system to battle tumors-has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression-free survival and the immune response. Progression-free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression-free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design. Copyright © 2018 John Wiley & Sons, Ltd.

Hyperargininemia: 7-month follow-up under sodium benzoate therapy in an Italian child presenting progressive spastic paraparesis, cognitive decline, and novel mutation in ARG1 gene.

PubMed

Baranello, Giovanni; Alfei, Enrico; Martinelli, Diego; Rizzetto, Manuela; Cazzaniga, Fabiana; Dionisi-Vici, Carlo; Gellera, Cinzia; Castellotti, Barbara

2014-09-01

Hyperargininemia due to mutations in ARG1 gene is an autosomal recessive inborn error of metabolism caused by a defect in the final step of the urea cycle. Common clinical presentation is a variable association of progressive spastic paraparesis, epilepsy, and cognitive deficits. We describe the clinical history of an Italian child presenting progressive spastic paraparesis, carrying a new homozygous missense mutation in the ARG1 gene. A detailed clinical, biochemical, and neurophysiological follow-up after 7 months of sodium benzoate therapy is reported. Laboratory findings, gait abnormalities, spastic paraparesis, and electroencephalographic and neurophysiological abnormalities remained quite stable over the follow-up. Conversely, a mild cognitive deterioration has been detected by means of the neuropsychologic assessment. Further longitudinal studies by means of longer follow-up and using clinical, biochemical, radiological, and neurophysiological assessments are needed in such patients to describe natural history and monitor the effects of treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

Country actions to meet UN commitments on non-communicable diseases: a stepwise approach.

PubMed

Bonita, Ruth; Magnusson, Roger; Bovet, Pascal; Zhao, Dong; Malta, Deborah C; Geneau, Robert; Suh, Il; Thankappan, Kavumpurathu Raman; McKee, Martin; Hospedales, James; de Courten, Maximilian; Capewell, Simon; Beaglehole, Robert

2013-02-16

Strong leadership from heads of state is needed to meet national commitments to the UN political declaration on non-communicable diseases (NCDs) and to achieve the goal of a 25% reduction in premature NCD mortality by 2025 (the 25 by 25 goal). A simple, phased, national response to the political declaration is suggested, with three key steps: planning, implementation, and accountability. Planning entails mobilisation of a multisectoral response to develop and support the national action plan, and to build human, financial, and regulatory capacity for change. Implementation of a few priority and feasible cost-effective interventions for the prevention and treatment of NCDs will achieve the 25 by 25 goal and will need only few additional financial resources. Accountability incorporates three dimensions: monitoring of progress, reviewing of progress, and appropriate responses to accelerate progress. A national NCD commission or equivalent, which is independent of government, is needed to ensure that all relevant stakeholders are held accountable for the UN commitments to NCDs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Progress on the biomarkers for tuberculosis diagnosis.

PubMed

Fu, Tiwei; Xie, Jianping

2011-01-01

Tuberculosis (TB) remains a major threat to global health. Biomarkers derived from pathogen-host interaction can facilitate the monitoring of active TB. The recent progress regarding such biomarkers is summarized, including those can be used from serum, sputum, urine, or breath monitoring. A wide range of potential biomarkers such as protein antigens, cell-free nucleic acids, and lipoarabinomannose were compiled. The possible use of biomarkers for infection identification and monitoring drug efficacy are also presented.

Progress Monitoring in Middle School Mathematics: Options and Issues

ERIC Educational Resources Information Center

Foegen, Anne

2008-01-01

This study investigated the technical features of six potential progress-monitoring measures in mathematics appropriate for use at the middle school level, including two commercially available measures for sixth-grade mathematics, two measures used in previous middle school studies, and two new measures of numeracy concepts. Five hundred…

Language Assessment in a Snap: Monitoring Progress up to 36 Months

ERIC Educational Resources Information Center

Gilkerson, Jill; Richards, Jeffrey A.; Greenwood, Charles R.; Montgomery, Judy K.

2017-01-01

This article describes the development and validation of the Developmental Snapshot, a 52-item parent questionnaire on child language and vocal communication development that can be administered monthly and scored automatically. The Snapshot was created to provide an easily administered monthly progress monitoring tool that enables parents to…

Advancing Stage 2 Research on Measures for Monitoring Kindergarten Reading Progress

ERIC Educational Resources Information Center

Clemens, Nathan H.; Soohoo, Michelle M.; Wiley, Colby P.; Hsiao, Yu-Yu; Estrella, Ivonne; Allee-Smith, Paula J.; Yoon, Myeongsun

2018-01-01

Although several measures exist for frequently monitoring early reading progress, little research has specifically investigated their technical properties when administered on a frequent basis with kindergarten students. In this study, kindergarten students (N = 137) of whom the majority was receiving supplemental intervention for reading skills…

Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer.

PubMed

Goldberg, Richard M; Montagut, Clara; Wainberg, Zev A; Ronga, Philippe; Audhuy, François; Taieb, Julien; Stintzing, Sebastian; Siena, Salvatore; Santini, Daniele

2018-01-01

The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line. We conducted a non-systematic literature search in PubMed and reviewed published and ongoing clinical trials, focusing on later-line cetuximab reuse in patients with mCRC. Evidence from multiple studies suggests that cetuximab can be an efficacious and tolerable treatment when continued or when fit patients with mCRC are retreated with it after a break from anti-EGFR therapy. Furthermore, on the basis of available preclinical and clinical evidence, we propose that longitudinal monitoring of RAS status may identify patients suitable for such a strategy. Patients who experience progression on cetuximab plus chemotherapy but have maintained RAS wt tumour status may benefit from continuation of cetuximab with a chemotherapy backbone switch because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion of RAS- mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose that RAS status determination at disease progression by liquid, needle or excisional biopsy may identify patients eligible for cetuximab continuation and rechallenge. With this approach, treatment benefit can be extended, adding to established continuum-of-care strategies in patients with mCRC.

Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy.

PubMed

Nakao, Naoyuki; Seno, Hachiro; Kasuga, Hirotake; Toriyama, Takanobu; Kawahara, Hirohisa; Fukagawa, Masafumi

2004-01-01

In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease. Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment. Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34-0.78, p = 0.01) and treatments (0.58, 0.45-0.99, 0.03), but not 24-hour ABP (0.98, 0.89-2.01, 0.17). The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade. 2004 S. Karger AG, Basel

Therapeutics of diabetes mellitus: focus on insulin analogues and insulin pumps.

PubMed

Valla, Vasiliki

2010-01-01

Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

Advances in mechanisms, diagnosis, and treatment of pernicious anemia.

PubMed

Rojas Hernandez, Cristhiam M; Oo, Thein Hlaing

2015-03-01

Pernicious anemia (PA) is an entity initially described in 1849 as a condition that consisted of pallor, weakness, and progressive health decline. Since then several advances led to the conclusion that PA is an autoimmune disease characterized by the deficient absorption of dietary cobalamin. It is currently recognized as the most common cause of cobalamin deficiency worldwide. We hereby review the current understanding of the disease and its neurological, hematological, and biochemical manifestations with emphasis on the diagnostic approach, treatment, and monitoring strategies. We propose an algorithm for the diagnostic approach considering the current performance and limitations of the available diagnostic tools for evaluation of cobalamin status and the presence of autoimmune chronic atrophic gastritis (CAG). Patients with PA require lifelong treatment with cobalamin replacement therapy. The current widely available treatment can be provided through enteral or parenteral cobalamin supplements, with comparable efficacy and tolerability.

Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02).

PubMed

Lee, Ji Yun; Qing, Xu; Xiumin, Wei; Yali, Bai; Chi, Sangah; Bak, So Hyeon; Lee, Ho Yun; Sun, Jong-Mu; Lee, Se-Hoon; Ahn, Jin Seok; Cho, Eun Kyung; Kim, Dong-Wan; Kim, Hye Ryun; Min, Young Joo; Jung, Sin-Ho; Park, Keunchil; Mao, Mao; Ahn, Myung-Ju

2016-02-09

We hypothesized that plasma-based EGFR mutation analysis for NSCLC may be feasible for monitoring treatment response to EGFR TKIs and also predict drug resistance.Clinically relevant mutations including exon 19 deletion (ex19del), L858R and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples (n = 367) from 81 NSCLC patients treated with EGFR TKI. Of a total 58 baseline cell-free DNA (cfDNA) samples available for ddPCR analysis, 43 (74.1%) had the same mutation in the matched tumors (clinical sensitivity: 70.8% [17/24] for L858R and 76.5% [26/34] for ex19del). The concordance rates of plasma with tissue-based results of EGFR mutations were 87.9% for L858R and 86.2% for ex19del. All 40 patients who were detected EGFR mutations at baseline showed a dramatic decrease of mutant copies (>50%) in plasma during the first two months after treatment. Median progression-free survival (PFS) was 10.1 months for patients with undetectable EGFR v 6.3 months for detectable EGFR mutations in blood after two-month treatment (HR 3.88, 95% CI 1.48-10.19, P = 0.006). We observed emerging resistance with early detection of T790M as a secondary mutation in 14 (28.6%) of 49 patients. Plasma-based EGFR mutation analysis using ddPCR can monitor treatment response to EGFR TKIs and can lead to early detection of EGFR TKIs resistance. Further studies confirming clinical implications of EGFR mutation in plasma are warranted to guide optimal therapeutic strategies upon knowledge of treatment response and resistance.

Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

PubMed

Pozzilli, C; Prosperini, L; Sbardella, E; De Giglio, L; Onesti, E; Tomassini, V

2005-12-01

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

Fluorescence lifetime imaging and its applications in cellular microenvironment measurement and auxiliary diagnosis

NASA Astrophysics Data System (ADS)

Luo, Teng; Levchenko, Svitlana M.; Pliss, Artem; Peng, Xiao; Yan, Wei; Prasad, Paras N.; Liu, Liwei; Qu, Junle

2018-02-01

We present our recent work on the applications of fluorescence lifetime imaging microscopy(FLIM), including the monitoring of macromolecule dynamic changes in the nucleolar compartments and the auxiliary diagnosis of H and E-stained sections. We demonstrated the capability of FLIM to measure protein concentration in the specific cellular compartments in live cells. We proposed to use FLIM to monitor changes in intracellular protein concentration caused by various factors e.g. cell cycle progression, drug treatment etc. In the future, FLIM technology is expected to be combined with super-resolution optical imaging. FLIM with molecular resolution will have the potential to serve as a powerful tool for discovering new phenomena and revealing new mechanisms in biomedical research, which will effectively promote the development of life science.

Near-infrared spectrometry in pregnancy: progress and perspectives, a review of literature

PubMed Central

Jarraya, Anouar; Mohamed, Smaoui; Sofiene, Laabidi; Kolsi, Kamel

2016-01-01

Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of in vivo oxygenation in selected tissues. It has been used primarily as a research tool for several years, but it is seeing wider application in the clinical arena all over the world. It was recently used to monitor brain circulation in cardiac surgery, carotid endarteriectomy, neurosurgery and robotic surgery. According to the few studies used NIRS in pregnancy, it may be helpful to assess the impact of severe forms of preeclampsia on brain circulation, to evaluate the efficacy of different treatments. It may also be used during cesarean section to detect earlier sudden complications. The evaluation of placental function via abdominal maternal approach to detect fetal growth restriction is a new field of application of NIRS. PMID:27200144

Near-infrared spectrometry in pregnancy: progress and perspectives, a review of literature.

PubMed

Jarraya, Anouar; Mohamed, Smaoui; Sofiene, Laabidi; Kolsi, Kamel

2016-01-01

Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of in vivo oxygenation in selected tissues. It has been used primarily as a research tool for several years, but it is seeing wider application in the clinical arena all over the world. It was recently used to monitor brain circulation in cardiac surgery, carotid endarteriectomy, neurosurgery and robotic surgery. According to the few studies used NIRS in pregnancy, it may be helpful to assess the impact of severe forms of preeclampsia on brain circulation, to evaluate the efficacy of different treatments. It may also be used during cesarean section to detect earlier sudden complications. The evaluation of placental function via abdominal maternal approach to detect fetal growth restriction is a new field of application of NIRS.

Integrating Condition Indicators and Usage Parameters for Improved Spiral Bevel Gear Health Monitoring

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Handschuh, Robert F.; Delgado, Irebert R.

2013-01-01

The objective of this study was to illustrate the importance of combining Health Usage Monitoring Systems (HUMS) data with usage monitoring system data when detecting rotorcraft transmission health. Six gear sets were tested in the NASA Glenn Spiral Bevel Gear Fatigue Rig. Damage was initiated and progressed on the gear and pinion teeth. Damage progression was measured by debris generation and documented with inspection photos at varying torque values. A contact fatigue analysis was applied to the gear design indicating the effect temperature, load and reliability had on gear life. Results of this study illustrated the benefits of combining HUMS data and actual usage data to indicate progression of damage for spiral bevel gears.

Integrating Condition Indicators and Usage Parameters for Improved Spiral Bevel Gear Health Monitoring

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Handschuh, Robert F.; Delgado, Irebert, R.

2013-01-01

The objective of this study was to illustrate the importance of combining Health Usage Monitoring Systems (HUMS) data with usage monitoring system data when detecting rotorcraft transmission health. Three gear sets were tested in the NASA Glenn Spiral Bevel Gear Fatigue Rig. Damage was initiated and progressed on the gear and pinion teeth. Damage progression was measured by debris generation and documented with inspection photos at varying torque values. A contact fatigue analysis was applied to the gear design indicating the effect temperature, load and reliability had on gear life. Results of this study illustrated the benefits of combining HUMS data and actual usage data to indicate progression of damage for spiral bevel gears.

A beam monitor based on MPGD detectors for hadron therapy

NASA Astrophysics Data System (ADS)

Altieri, P. R.; Di Benedetto, D.; Galetta, G.; Intonti, R. A.; Mercadante, A.; Nuzzo, S.; Verwilligen, P.

2018-02-01

Remarkable scientific and technological progress during the last years has led to the construction of accelerator based facilities dedicated to hadron therapy. This kind of technology requires precise and continuous control of position, intensity and shape of the ions or protons used to irradiate cancers. Patient safety, accelerator operation and dose delivery should be optimized by a real time monitoring of beam intensity and profile during the treatment, by using non-destructive, high spatial resolution detectors. In the framework of AMIDERHA (AMIDERHA - Enhanced Radiotherapy with HAdron) project funded by the Ministero dell'Istruzione, dell'Università e della Ricerca (Italian Ministry of Education and Research) the authors are studying and developing an innovative beam monitor based on Micro Pattern Gaseous Detectors (MPDGs) characterized by a high spatial resolution and rate capability. The Monte Carlo simulation of the beam monitor prototype was carried out to optimize the geometrical set up and to predict the behavior of the detector. A first prototype has been constructed and successfully tested using 55Fe, 90Sr and also an X-ray tube. Preliminary results on both simulations and tests will be presented.

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

PubMed

Valdora, Francesca; Cutrona, Giovanna; Matis, Serena; Morabito, Fortunato; Massucco, Carlotta; Emionite, Laura; Boccardo, Simona; Basso, Luca; Recchia, Anna Grazia; Salvi, Sandra; Rosa, Francesca; Gentile, Massimo; Ravina, Marco; Pace, Daniele; Castronovo, Angela; Cilli, Michele; Truini, Mauro; Calabrese, Massimo; Neri, Antonino; Neumaier, Carlo Emanuele; Fais, Franco; Baio, Gabriella; Ferrarini, Manlio

2016-11-01

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Despite its indolent nature, CLL remains an incurable disease. Herein we aimed to monitor CLL disease engraftment and, progression/regression in a xenograft CLL mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Spleen contrast enhancement, quantified as percentage change in signal intensity upon USPIO administration, demonstrated a difference due to a reduced USPIO uptake, in the spleens of mice injected with CLL cells (NSG-CLL, n=71) compared to controls (NSG-CTR, n=17). These differences were statistically significant both after 2 and 4weeks from CLL cells injection. In addition comparison of mice treated with rituximab with untreated controls for changes in spleen iron uptake confirmed that it is possible to monitor treatment efficacy in this mouse model of CLL using USPIO-enhanced MRI. Further applications could include the preclinical in vivo monitoring of new therapies and the clinical evaluation of CLL patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment Expectations for Cognitive-Behavioral Therapy and Light Therapy for Seasonal Affective Disorder: Change Across Treatment and Relation to Outcome

PubMed Central

Meyerhoff, Jonah; Rohan, Kelly J.

2016-01-01

Objective To examine the dynamic relationship between treatment expectations and treatment outcome over the course of a clinical trial for winter seasonal affective disorder (SAD). Method Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6-weeks of group-delivered cognitive-behavioral therapy for SAD (CBT-SAD) or light therapy (LT). The majority was female (83.6%) and white (92.1%), with a mean age of 45.6 years. Treatment expectations for CBT-SAD and LT were assessed using a modification of the Treatment Expectancy and Credibility Survey (Borkovec & Nau, 1972). Depression severity was assessed using the Beck Depression Inventory-Second Edition (Beck, Steer, & Brown, 1996). All measures were administered at pre-treatment, mid-treatment, and post-treatment. Results As treatment progressed, expectations for the treatment received increased across time steeply in CBT-SAD patients and moderately in LT patients. Collapsing across time, patients with higher treatment expectations had lower depression severity than those with lower treatment expectations. In a cross-lagged panel path analysis, there was a significant effect of treatment expectations at mid-treatment on depression severity at post-treatment among CBT-SAD patients. Conclusions Treatment expectations changed across treatment, affected outcome, and should be assessed and monitored repeatedly throughout treatment. Findings suggest that treatment expectations at mid-treatment are a mechanism by which CBT-SAD reduces depression, which should be replicated in SAD samples and examined for generalizability to non-seasonal depression. These findings underscore the importance of further research examining treatment expectations in mediating CBT’s effects in depression and other types of psychopathology. Public Health Significance This study highlights the importance of monitoring treatment expectations repeatedly during treatment regardless of treatment type. Moreover, therapists administering cognitive-based therapy for depression should actively attend to the degree of patient “buy-in” early in treatment as it has clear indications for depression severity at treatment endpoint. PMID:27281373

Epigenetic regulation in myelodysplastic syndromes: implications for therapy.

PubMed

Vigna, Ernesto; Recchia, Anna Grazia; Madeo, Antonio; Gentile, Massimo; Bossio, Sabrina; Mazzone, Carla; Lucia, Eugenio; Morabito, Lucio; Gigliotti, Vincenzo; Stefano, Laura De; Caruso, Nadia; Servillo, Pasquale; Franzese, Stefania; Fimognari, Filippo; Bisconte, Maria Grazia; Gentile, Carlo; Morabito, Fortunato

2011-04-01

Myelodysplastic syndromes (MDS), characterized by ineffective hematopoiesis and dysplasia in one or more lineages, produce life-threatening cytopenias and progress to acute myeloid leukemia (AML). Growing evidence suggests that targeting epigenetic mechanisms improves MDS/AML pathophysiology. This review provides an understanding of studies investigating novel agents published up to January 2011 aimed at normalizing and monitoring the epigenetic profile of the MDS cancer cell. The authors discuss how non-intensive epigenetic therapy can 're-programme' gene expression patterns of abnormal hematopoiesis in MDS. Recently FDA-approved DNA-methyltransferase inhibitors, 5-azacytidine and 5-aza-2'-deoxycytidine or decitabine, represent frontline nonablative treatments, while combinations with histone deacetylase inhibitors show promising synergism in preclinical and Phase I/II trials in tumor suppressor gene re-expression and overall survival. Additional epigenetic mechanisms including non-encoding transcripts with inhibitory posttranscriptional regulatory functions, such as microRNAs, though not fully understood, present novel molecular and clinical implications in these disorders. Alongside current single-agent epigenetic regimens, combination therapies represent potentially effective options for intermediate-2 and high-risk MDS. Methylation profiles and gene mutation predictors provide promising areas of development for monitoring MDS disease progression and outcome, while targeting microRNA dysregulation represents an important therapeutic goal.

Care and Neurorehabilitation in the Disorder of Consciousness: A Model in Progress

PubMed Central

Dolce, Giuliano; Arcuri, Francesco; Carozzo, Simone; Cortese, Maria Daniela; Greco, Pierpaolo; Lucca, Lucia Francesca; Pignolo, Loris; Pugliese, Maria Elena

2015-01-01

The operational model and strategies developed at the Institute S. Anna-RAN to be applied in the care and neurorehabilitation of subjects with disorders of consciousness (DOC) are described. The institute units are sequentially organized to guarantee appropriate care and provide rehabilitation programs adapted to the patients' clinical condition and individual's needs at each phase of evolution during treatment in a fast turnover rate. Patients eligible of home care are monitored remotely. Transferring advanced technology to a stage of regular operation is the main mission. Responsiveness and the time windows characterized by better residual responsiveness are identified and the spontaneous/induced changes in the autonomic system functional state and biological parameters are monitored both in dedicated sessions and by means of an ambient intelligence platform acquiring large databases from traditional and innovative sensors and interfaced with knowledge management and knowledge discovery systems. Diagnosis of vegetative state/unresponsive wakefulness syndrome or minimal conscious state and early prognosis are in accordance with the current criteria. Over one thousand patients with DOC have been admitted and treated in the years 1998–2013. The model application has progressively shortened the time of hospitalization and reduced costs at unchanged quality of services. PMID:25893211

The Telecommunications and Data Acquisition Progress Report 42-123

NASA Technical Reports Server (NTRS)

Yuen, Joseph H. (Editor)

1995-01-01

The progress of research programs monitored by the Jet Propulsion Laboratory's Telecommunications and Mission Operations Directorate (TMOD) are presented in this quarterly document. Areas monitored include space communications, radio navigation, radio science, ground-based radio and radar astronomy, information systems, and all other communication and research technology activities for the Deep Space Network (DSN).

Curriculum-Based Measurement of Reading Growth: Weekly versus Intermittent Progress Monitoring

ERIC Educational Resources Information Center

Jenkins, Joseph; Schulze, Margaret; Marti, Allison; Harbaugh, Allen G.

2017-01-01

We examined the idea that leaner schedules of progress monitoring (PM) can lighten assessment demands without undermining decision-making accuracy. Using curriculum-based measurement of reading, we compared effects on decision accuracy of 5 intermittent PM schedules relative to that of every-week PM. For participating students with high-incidence…

Robust Regression for Slope Estimation in Curriculum-Based Measurement Progress Monitoring

ERIC Educational Resources Information Center

Mercer, Sterett H.; Lyons, Alina F.; Johnston, Lauren E.; Millhoff, Courtney L.

2015-01-01

Although ordinary least-squares (OLS) regression has been identified as a preferred method to calculate rates of improvement for individual students during curriculum-based measurement (CBM) progress monitoring, OLS slope estimates are sensitive to the presence of extreme values. Robust estimators have been developed that are less biased by…

Assessing and Monitoring Student Progress in an E-Learning Personnel Preparation Environment.

ERIC Educational Resources Information Center

Meyen, Edward L.; Aust, Ronald J.; Bui, Yvonne N.; Isaacson, Robert

2002-01-01

Discussion of e-learning in special education personnel preparation focuses on student assessment in e-learning environments. It includes a review of the literature, lessons learned by the authors from assessing student performance in e-learning environments, a literature perspective on electronic portfolios in monitoring student progress, and the…

Educational Progress Indicator (E.P.I.): Synthetic Indicator for Monitoring Education. Contribution to Education for All.

ERIC Educational Resources Information Center

Camara, Boubacar

This publication complements the "Education for All" program and is intended to provide a comprehensive and operational indicator for monitoring education. As a synthetic tool, the Educational Progress Indicator (EPI) facilitates the analytical assessment and projection work of educational planners, managers, actors, and policymakers. The EPI…

Daily Behavior Report Cards as Evidence-Based Practice for Teachers

ERIC Educational Resources Information Center

Vannest, Kimberly J.; Burke, Mack D.; Sauber, Stephanie B.; Davis, John L.; Davis, Cole R.

2011-01-01

Easy-to-use progress-monitoring and intervention techniques are attractive because most teachers are crunched for time and teacher instructional time is often consumed with paperwork, especially for progress monitoring and discipline. Some studies indicate up to 50% of a special educator's time may be spent on paperwork. Methods that serve a dual…

Monitoring Progress of Students Who Are Deaf or Hard of Hearing

ERIC Educational Resources Information Center

Rose, Susan

2007-01-01

Federal and state legislation has placed a renewed emphasis on accountability and academic outcomes among students who are deaf or hard of hearing. While much attention is given to norm-referenced standardized testing accommodations, there is a need for functional formative assessments for the purpose of monitoring students' academic progress.…

Progress Monitoring in Grade 5 Science for Low Achievers

ERIC Educational Resources Information Center

Vannest, Kimberly J.; Parker, Richard; Dyer, Nicole

2011-01-01

This article presents procedures and results from a 2-year project developing science key vocabulary (KV) short tests suitable for progress monitoring Grade 5 science in Texas public schools using computer-generated, -administered, and -scored assessments. KV items included KV definitions and important usages in a multiple-choice cloze format. A…

Effect of Technology-Enhanced Continuous Progress Monitoring on Math Achievement

ERIC Educational Resources Information Center

Ysseldyke, Jim; Bolt, Daniel M.

2007-01-01

We examined the extent to which use of a technology-enhanced continuous progress monitoring system would enhance the results of math instruction, examined variability in teacher implementation of the program, and compared math results in classrooms in which teachers did and did not use the system. Classrooms were randomly assigned to within-school…

Psychometric Aspects of Pupil Monitoring Systems

ERIC Educational Resources Information Center

Glas, Cees A. W.; Geerlings, Hanneke

2009-01-01

Pupil monitoring systems support the teacher in tailoring teaching to the individual level of a student and in comparing the progress and results of teaching with national standards. The systems are based on the availability of an item bank calibrated using item response theory. The assessment of the students' progress and results can be further…

Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

PubMed Central

Daubenbüchel, Anna M. M.; Müller, Hermann L.

2015-01-01

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients. PMID:26239246

Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

PubMed Central

Zwaan, C. Michel; Kolb, Edward A.; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S.J.M.; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E.S.; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C.; Rizzari, Carmelo; Rubnitz, Jeffrey E.; Smith, Owen P.; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M.; Creutzig, Ursula; Kaspers, Gertjan J.L.

2015-01-01

Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML—supportive care—and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

PubMed Central

Nguyen, Lich Thi; Sharma, Ashish Ranjan; Chakraborty, Chiranjib; Saibaba, Balaji; Ahn, Moo-Eob; Lee, Sang-Soo

2017-01-01

Osteoarthritis (OA) is a degenerative disease of the joints and is one of the leading causes of disability in adults. However, there are no key therapeutics for OA and medical treatment is based on managing the symptoms and slowing down progression of the disease. Diagnostics based on clinical examination and radiography have provided little information about metabolic changes in joint tissues, disease onset and progression. Due to lack of effective methods for early detection and evaluation of treatment outcome, the measurement of biochemical markers (biomarkers) shows promise as a prospective method aiding in disease monitoring. OA biomarkers that are present in biological fluids such as blood, urine and synovial fluid, sources that are easily isolated from body, are of particular interest. Moreover, there are increasingly more studies identifying and developing new biomarkers for OA. In this review, efforts have been made to summarize the biomarkers that have been reported in recent studies on patients. We also tried to classify biomarkers according to tissue metabolism (bone, cartilage and synovial metabolism markers), pathological pathways (inflammatory and genetic markers) and biological function (chemokines, growth factors, acute phase proteins, etc.). PMID:28287489

Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

PubMed

Zwaan, C Michel; Kolb, Edward A; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S J M; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E S; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C; Rizzari, Carmelo; Rubnitz, Jeffrey E; Smith, Owen P; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M; Creutzig, Ursula; Kaspers, Gertjan J L

2015-09-20

Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. © 2015 by American Society of Clinical Oncology.

Multimodal Imaging in Diabetic Macular Edema.

PubMed

Acón, Dhariana; Wu, Lihteh

2018-01-01

Throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs. In the past, fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema (DME). Today, despite the moderate correlation between macular thickness and functional outcomes, spectral domain optical coherence tomography (SD-OCT) has become the DME workhorse in clinical practice. Several SD-OCT biomarkers have been looked at including presence of epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal layers, central macular thickness, integrity of the ellipsoid layer, and subretinal fluid, among others. Emerging imaging modalities include fundus autofluorescence, macular pigment optical density, fluorescence lifetime imaging ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease, monitor disease progression, and assess response to treatment. Spectral domain OCT is the most commonly performed imaging modality in the management of DME. However, reliable biomarkers have yet to be identified. Machine learning may provide treatment algorithms based on multimodal imaging. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Results of a Phase II Trial of Gemcitabine plus Doxorubicin in Patients with Recurrent Head and Neck Cancers: Serum C18-ceramide as a Novel Biomarker for Monitoring Response

PubMed Central

Saddoughi, Sahar A.; Garrett-Mayer, Elizabeth; Chaudhary, Uzair; O’Brien, Paul; Afrin, Larry; Day, Terry A.; Gillespie, M. Boyd; Sharma, Anand; Wilhoit, Christina; Bostick, Robin; Senkal, Can E.; Hannun, Yusuf A.; Bielawski, Jacek; Simon, George; Shirai, Keisuke; Ogretmen, Besim

2011-01-01

Purpose Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with GEM/DOX would be efficacious via reconstitution of C18-ceramide signaling in HNSCC patients for whom first-line platinum-based therapy failed. Experimental Design Patients received GEM (1,000 mg/m2) and DOX (25 mg/m2) on days 1 and 8, every 21 days, until disease progression. After completion of 2 treatment cycles, patients were assessed radiographically, and serum samples were taken for sphingolipid measurements. Results We enrolled 18 patients in the trial, who were evaluable for toxicity, and 17 for response. The most common toxicity was neutropenia, observed in 9 of 18 patients, and there were no major non-hematological toxicities. Of the 17 patients, 5 patients had progressive disease (PD), 1 had complete response (CR), 3 exhibited partial response (PR), and 8 had stable disease (SD). The median progression-free survival (PFS) was 1.6 months (95% CI, 1.4, 4.2) with a median survival of 5.6 months (95% CI, 3.8, 18.2). Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C18-ceramide elevation in patients with CR/PR/SD in comparison to patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment. Conclusions Our data suggest that the GEM/DOX combination could represent an effective treatment for some patients with recurrent or metastatic HNSCC, and that serum C18-ceramide elevation might be a novel serum biomarker of chemotherapy response. PMID:21791630

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

PubMed

Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

Photoacoustic microscopy of complex regional pain syndrome type I (CRPS-1) after stellate ganglion blocks in vivo

NASA Astrophysics Data System (ADS)

Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

2015-03-01

We used photoacoustic microscopy (PAM) to assist diagnoses and monitor the progress and treatment outcome of complex regional pain syndrome type 1 (CRPS-1). Blood vasculature and oxygen saturation (sO2) were imaged by PAM in eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both the vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB.

A Novel Microfluidic Device for Isolation of Circulating Tumor Cells from Pancreatic Cancer Blood Samples.

PubMed

Varillas, Jose I; Chen, Kangfu; Zhang, Jinling; George, Thomas J; Hugh Fan, Z

2017-01-01

Enumeration of circulating tumor cells (CTCs) can provide valuable prognostic information to guide cancer treatment as well as help monitor disease progression. Analysis of these rare malignant cells has the potential to further our understanding of cancer metastasis by gaining insights into CTC characteristics and properties. Microfluidics presents a unique platform to isolate and study CTCs. In this chapter, we describe the detailed procedures for the fabrication and use of a microfluidic device to detect CTCs from the blood of pancreatic cancer patients.

Hyperkalemia by Euro-Collins solution in anesthesia for renal transplantation: a case report.

PubMed

Hirata, Eunice Sizue; Pereira, Rosa Inês Costa; Filho, Gentil Alves; Braga, Angélica de Fátima Assunção

2013-01-01

To describe anesthesia for renal transplantation that progressed to a sharp potassium increase after kidney reperfusion with Euro-Collins' solution in the operative field. We will also report on diagnosis and treatment used. The use of infusion solutions in the surgical field requires careful monitoring, such as electrocardiography, measurement of serum potassium, and availability of calcium gluconate, insulin, and albuterol for immediate use. The replacement of Euro-Collins' solution for saline solution immediately before the implant may be a useful option in patients with high levels of potassium.

Progress Toward Cleanup of Operable Unit 1 Groundwater at the US DOE Mound, Ohio, Site: Success of a Phase-Combined Remedy – 15310

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

Hooten, Gwendolyn; Cato, Rebecca; Looney, Brian

2015-03-01

Operable Unit 1 (OU-1) soil and groundwater have been affected by volatile organic compounds (VOC) Present groundwater remedy is collection, treatment, and disposal (pump and treat [P&T]) Several combinations of technologies were used to address soil and groundwater contamination Monitored natural attenuation (MNA) is a viable alternative Majority of source term has been excavated VOC concentrations in groundwater have decreased Attenuation mechanisms have been observed in the subsurface at OU-1

Clonal evolution in myelodysplastic syndromes

PubMed Central

da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H.

2017-01-01

Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions. PMID:28429724

Orthodontic treatment for a patient with multiple sclerosis

PubMed Central

Bakathir, Manal A

2017-01-01

Multiple sclerosis (MS) is a chronic, autoimmune inflammatory disorder of the central nervous system (CNS) that affects myelinated axons, destroying the myelin and damaging axons to varying degrees. The course of MS is highly varied and unpredictable. Metals used during orthodontic treatment can negatively affect imaging techniques used to diagnose and monitor the progression of MS, while medications used to treat MS can negatively affect orthodontic tooth movement. The present case report highlights some of the challenges encountered during orthodontic treatment of a patient with MS and how to overcome them. The patient was a 20-year-old woman with complaints of diastema and spacing in the upper arch. Although closing the spaces was challenging due to some of the MS medications, she was treated successfully, without complications, within 20 months using closing loops. PMID:28717636

Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.

PubMed

Scholtens, A; Geukes Foppen, M H; Blank, C U; van Thienen, J V; van Tinteren, H; Haanen, J B

2015-03-01

Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04). Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis.

PubMed

Obici, Laura; Kuks, Jan B; Buades, Juan; Adams, David; Suhr, Ole B; Coelho, Teresa; Kyriakides, Theodore

2016-02-01

These recommendations highlight recent experience in genetic counselling for the severe autosomal-dominant, late-onset transthyretin familial amyloid polyneuropathy (TTR-FAP) disease, and present a structured approach towards identification and monitoring of asymptomatic carriers of the mutated gene. The effectiveness of current treatment options is still limited in patients with TTR-FAP beyond stage I. Diagnosis in the early stages of TTR-FAP is essential to prevent or delay the progression of disease. Existing legal and cultural issues differ among countries within Europe. Experts of the European Network for TTR-FAP (ATTReuNET) concluded that genetic counselling for diagnosed individuals and at-risk family members is mostly beneficial and should be carried out with care by trained professionals. Systematic and regular monitoring of an asymptomatic carrier is necessary to detect early signs of TTR-FAP and maximize the effectiveness of treatment. This includes five areas of assessment: history/clinical examination, sensorimotor function, autonomic dysfunction, cardiac function, and renal function. At least two related symptoms and positive biopsy findings are required to confirm diagnosis of TTR-FAP. Early detection of TTR-FAP is essential to improve the prognosis of TTR-FAP. ATTReuNET recommends genetic counselling and routine monitoring for asymptomatic carriers of TTR-FAP.

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results

PubMed Central

Hughes, Timothy; Deininger, Michael; Hochhaus, Andreas; Branford, Susan; Radich, Jerald; Kaeda, Jaspal; Baccarani, Michele; Cortes, Jorge; Cross, Nicholas C. P.; Druker, Brian J.; Gabert, Jean; Grimwade, David; Hehlmann, Rüdiger; Kamel-Reid, Suzanne; Lipton, Jeffrey H.; Longtine, Janina; Martinelli, Giovanni; Saglio, Giuseppe; Soverini, Simona; Stock, Wendy; Goldman, John M.

2006-01-01

The introduction in 1998 of imatinib mesylate (IM) revolutionized management of patients with chronic myeloid leukemia (CML) and the second generation of tyrosine kinase inhibitors may prove superior to IM. Real-time quantitative polymerase chain reaction (RQ-PCR) provides an accurate measure of the total leukemiacell mass and the degree to which BCR-ABL transcripts are reduced by therapy correlates with progression-free survival. Because a rising level of BCR-ABL is an early indication of loss of response and thus the need to reassess therapeutic strategy, regular molecular monitoring of individual patients is clearly desirable. Here we summarize the results of a consensus meeting that took place at the National Institutes of Health (NIH) in Bethesda in October 2005. We make suggestions for (1) harmonizing the differing methodologies for measuring BCR-ABL transcripts in patients with CML undergoing treatment and using a conversion factor whereby individual laboratories can express BCR-ABL transcript levels on an internationally agreed scale; (2) using serial RQ-PCR results rather than bone marrow cytogenetics or fluorescence in situ hybridization (FISH) for the BCR-ABL gene to monitor individual patients responding to treatment; and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing BCR-ABL kinase domain mutations. We recognize that our recommendations are provisional and will require revision as new evidence emerges. (Blood. 2006;108:28-37) PMID:16522812

Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers.

PubMed

Yamazaki, Masahiro; Hasegawa, Goji; Majima, Saori; Mitsuhashi, Kazuteru; Fukuda, Takuya; Iwase, Hiroya; Kadono, Mayuko; Asano, Mai; Senmaru, Takafumi; Tanaka, Muhei; Fukui, Michiaki; Nakamura, Naoto

2014-01-01

Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.

Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers

PubMed Central

2014-01-01

Background Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. Methods Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. Results Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. Conclusion These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress. PMID:24843385

Progress with anti-tumor necrosis factor therapeutics for the treatment of inflammatory bowel disease.

PubMed

Fernandes, Carlos; Allocca, Mariangela; Danese, Silvio; Fiorino, Gionata

2015-01-01

Anti-tumor necrosis factor (TNF) therapy is a valid, effective and increasingly used option in inflammatory bowel disease management. Nevertheless, further knowledge and therapeutic indications regarding these drugs are still evolving. Anti-TNF therapy may be essential to achieve recently proposed end points, namely mucosal healing, prevention of bowel damage and prevention of patient's disability. Anti-TNF drugs are also suggested to be more effective in early disease, particularly in early Crohn's disease. Moreover, its efficacy for prevention of postoperative recurrence in Crohn's disease is still debated. Costs and adverse effects, the relevance of drug monitoring and the possibility of anti-TNF therapy withdrawal in selected patients are still debated issues. This review aimed to describe and discuss the most relevant data about the progress with anti-TNF therapy for the management of inflammatory bowel disease.

[KIM-1 and NGAL as potential biomarkers for the diagnosis and cancer progression].

PubMed

Marchewka, Zofia; Tacik, Aneta; Piwowar, Agnieszka

2016-04-18

On the basis of scientific literature, there is growing evidence that KIM-1 and NGAL are interesting and promising biomarkers not only in acute and chronic inflammatory processes but also in oncogenesis. There are a number of studies which investigate their possible use in diagnosis, treatment and monitoring of therapy effectiveness. The results of recent research suggests that they may play an important role in standard oncology practice. Simultaneous measurement of KIM-1 and NGAL in urine can play a crucial role in carcinogenesis assessment and cancer progression. In the future, they can become rapid diagnostic indicators, which allow one to determine cancer subtype leading to biopsy replacement and therapy improvement. In the present work, beside biochemical characteristics of KIM-1 and NGAL, we will also discuss their role in the diagnosis and assessment of development of cancer.

Imaging tumor microscopic viscosity in vivo using molecular rotors

PubMed Central

Shimolina, Lyubov’ E.; Izquierdo, Maria Angeles; López-Duarte, Ismael; Bull, James A.; Shirmanova, Marina V.; Klapshina, Larisa G.; Zagaynova, Elena V.; Kuimova, Marina K.

2017-01-01

The microscopic viscosity plays an essential role in cellular biophysics by controlling the rates of diffusion and bimolecular reactions within the cell interior. While several approaches have emerged that have allowed the measurement of viscosity and diffusion on a single cell level in vitro, the in vivo viscosity monitoring has not yet been realized. Here we report the use of fluorescent molecular rotors in combination with Fluorescence Lifetime Imaging Microscopy (FLIM) to image microscopic viscosity in vivo, both on a single cell level and in connecting tissues of subcutaneous tumors in mice. We find that viscosities recorded from single tumor cells in vivo correlate well with the in vitro values from the same cancer cell line. Importantly, our new method allows both imaging and dynamic monitoring of viscosity changes in real time in live animals and thus it is particularly suitable for diagnostics and monitoring of the progress of treatments that might be accompanied by changes in microscopic viscosity. PMID:28134273

Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma.

PubMed

O'Donnell-Luria, Anne H; Lin, Alexander P; Merugumala, Sai K; Rohr, Frances; Waisbren, Susan E; Lynch, Rebecca; Tchekmedyian, Vatche; Goldberg, Aaron D; Bellinger, Andrew; McFaline-Figueroa, J Ricardo; Simon, Tracey; Gershanik, Esteban F; Levy, Bruce D; Cohen, David E; Samuels, Martin A; Berry, Gerard T; Frank, Natasha Y

2017-05-01

Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in mental status mirrored brain glutamine levels, as coma persisted for 48h after plasma ammonia normalized. We hypothesize that the slower clearance for brain glutamine levels accounts for the delay in improvement following initiation of treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic monitoring purposes in adult patients presenting with idiopathic hyperammonemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

PubMed

Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Validating the use of a luciferase labeled breast cancer cell line, MDA435LCC6, as a means to monitor tumor progression and to assess the therapeutic activity of an established anticancer drug, docetaxel (Dt) alone or in combination with the ILK inhibitor, QLT0267

PubMed Central

Anantha, Malathi; Warburton, Corinna; Waterhouse, Dawn; Yan, Hong; Yang, Young-joo; Strut, Dita; Osooly, Maryam; Masin, Dana; Bally, Marcel B

2011-01-01

A significant issue in drug efficacy studies is animal study design. Here we hypothesize that when evaluating new or existing therapeutics for the treatment of cancer, the location of disease burden will influence drug efficacy. To study this, female NCr nude mice were inoculated with luciferase-positive human breast cancer cells (LCC6WT-luc) orthotopically (o.t.), intraperitoneally (i.p.) or intracardiacly (i.c.) to create localized, ascites or disseminated disease, respectively. Tumor development was monitored using bioluminescence imaging. Docetaxel (Dt) pharmacokinetics and distribution to sites of tumor growth were determined. Disease progression was followed in animals treated with Dt alone and in combination with QLT0267, an integrin linked kinase inhibitor. Tumor related morbidity was most rapid when cells were inoculated i.c., where disease progression was observed in brain, ovaries, adrenal glands and lungs. Dt pharmacokinetics were comparable regardless of the model used (mean plasma AUC0–24 hrs 482.6 ng/ml*hr), however, Dt levels were lowest in those tissues developing disease following i.c. cell injection. Treatment with low dose Dt (5 mg/kg) increased overall survival and reduced tumor cell growth in all three models but the activity was greatest in mice with orthotopic tumors. Higher doses of Dt (15 mg/kg) was able to prolong survival in animals bearing i.p. tumors but not i.c. tumors. Addition of QLT0267 provided no added benefit above Dt alone in the disseminated model. These studies highlight a need for more comprehensive in vivo efficacy studies designed to assess multiple disease models and multiple endpoints, focusing analysis of drug parameters on the most chemoresistant disease. PMID:21358264

Permanent renal loss following tumor necrosis factor α antagonists for arthritis.

PubMed

Chen, Tzu-Jen; Yang, Ya-Fei; Huang, Po-Hao; Lin, Hsin-Hung; Huang, Chiu-Ching

2010-06-01

Tumor necrosis factor alpha (TNF-alpha) antagonists are now widely used in the treatment of aggressive rheumatoid arthritis and are generally well tolerated. Although rare, they could induce systemic lupus erythematosus, glomerulonephritis, and antineutrophil cytoplasmic antibody associated systemic vasculitis. Tumor necrosis factor alpha antagonists associated glomerulonephritis usually subsides after discontinuation of the therapy and subsequent initiation of corticosteroids and immunosuppressive agents. Here we describe crescentic glomerulonephritis progression to end-stage renal disease in a patient following two doses of TNF-alpha antagonists for the treatment of reactive arthritis. To our knowledge, dialysis dependent permanent renal loss after TNF-alpha antagonists has not yet been reported. We suggest the renal function should be closely monitored in patients treated with TNF-alpha antagonists by rheumatologists.

Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.

PubMed

Hampel, Harald; Frank, Richard; Broich, Karl; Teipel, Stefan J; Katz, Russell G; Hardy, John; Herholz, Karl; Bokde, Arun L W; Jessen, Frank; Hoessler, Yvonne C; Sanhai, Wendy R; Zetterberg, Henrik; Woodcock, Janet; Blennow, Kaj

2010-07-01

Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.

Treatment and rehabilitation of drug addicts in Singapore 1977-1982.

PubMed

Ng, B C

1984-01-01

In Singapore, the treatment and rehabilitation of drug addicts consist of detoxification, recuperation and orientation, indoctrination, physical training and work programme. This is followed by a Day Release Scheme to bridge the gap between the strict disciplinary regime and the free environment of the outside world. The addicts are given the opportunities to pursue academic studies. Two review committees monitor their progress. There has been a significant decrease in the total number of admission from 7084 in 1977 to 2043 in 1982. Over this period, there appears to be a drop in the number of youths recruited into drug abuse. At the same time, more and more of those who have been previously treated are coming into the drug scene.

The application of micro UAV in construction project

NASA Astrophysics Data System (ADS)

Kaamin, Masiri; Razali, Siti Nooraiin Mohd; Ahmad, Nor Farah Atiqah; Bukari, Saifullizan Mohd; Ngadiman, Norhayati; Kadir, Aslila Abd; Hamid, Nor Baizura

2017-10-01

In every outstanding construction project, there is definitely have an effective construction management. Construction management allows a construction project to be implemented according to plan. Every construction project must have a progress development works that is usually created by the site engineer. Documenting the progress of works is one of the requirements in construction management. In a progress report it is necessarily have a visual image as an evidence. The conventional method used for photographing on the construction site is by using common digital camera which is has few setback comparing to Micro Unmanned Aerial Vehicles (UAV). Besides, site engineer always have a current issues involving limitation of monitoring on high reach point and entire view of the construction site. The purpose of this paper is to provide a concise review of Micro UAV technology in monitoring the progress on construction site through visualization approach. The aims of this study are to replace the conventional method of photographing on construction site using Micro UAV which can portray the whole view of the building, especially on high reach point and allows to produce better images, videos and 3D model and also facilitating site engineer to monitor works in progress. The Micro UAV was flown around the building construction according to the Ground Control Points (GCPs) to capture images and record videos. The images taken from Micro UAV have been processed generate 3D model and were analysed to visualize the building construction as well as monitoring the construction progress work and provides immediate reliable data for project estimation. It has been proven that by using Micro UAV, a better images and videos can give a better overview of the construction site and monitor any defects on high reach point building structures. Not to be forgotten, with Micro UAV the construction site progress is more efficiently tracked and kept on the schedule.

Numerical modeling of thermal conductive heating in fractured bedrock.

PubMed

Baston, Daniel P; Falta, Ronald W; Kueper, Bernard H

2010-01-01

Numerical modeling was employed to study the performance of thermal conductive heating (TCH) in fractured shale under a variety of hydrogeological conditions. Model results show that groundwater flow in fractures does not significantly affect the minimum treatment zone temperature, except near the beginning of heating or when groundwater influx is high. However, fracture and rock matrix properties can significantly influence the time necessary to remove all liquid water (i.e., reach superheated steam conditions) in the treatment area. Low matrix permeability, high matrix porosity, and wide fracture spacing can contribute to boiling point elevation in the rock matrix. Consequently, knowledge of these properties is important for the estimation of treatment times. Because of the variability in boiling point throughout a fractured rock treatment zone and the absence of a well-defined constant temperature boiling plateau in the rock matrix, it may be difficult to monitor the progress of thermal treatment using temperature measurements alone. Copyright © 2010 The Author(s). Journal compilation © 2010 National Ground Water Association.

Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist.

PubMed

Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

2009-01-01

The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants were university students diagnosed with LTBI. The authors conducted a retrospective review of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken, characteristics of completers versus noncompleters, average time to treatment completion, and reported adverse drug events. The 9-month completion rate was 59%, and the 6-month completion rate was 67%. Among those not completing treatment, 15.2% experienced fatigue and 2.2% experienced a rash (p=.04 and p=.03, respectively). LTBI clinics are a unique niche for community pharmacies and can provide individualized patient care to ensure LTBI treatment adherence, monitoring for disease progression, and safety of INH.

Assessing the progress of rehabilitation in patients with ACL reconstruction using the International Knee Documentation Committee Subjective Knee Form

NASA Astrophysics Data System (ADS)

Leguizamon, J. H.; Braidot, A.; Catalfamo Formento, P.

2011-12-01

There are numerous assessment tools designed to provide information on the results of reconstructive surgery of anterior cruciate ligament (ACL). They are also used for monitoring progress and facilitating clinical decision-making during the rehabilitation process. A brief summary of some existing tools specifically designed to evaluate knee ligament injuries is presented in this article. Then, one of those outcome measures, the International Knee Documentation Committee Subjective Knee Form (IKDC) was applied to a group of patients (N = 10) who had undergone surgery for ACL reconstruction. The patients attended the same physiotherapy service and followed a unified rehabilitation protocol. The assessment was performed twice: four and six months after surgery. The results showed an improvement in the rehabilitation of most patients tested (verified by a difference equal to or greater than 9 points on the IKDC outcome between measurements 1 and 2). The IKDC probed to be an instrument of quick and easy application. It provided quantitative data about the progress of rehabilitation and could be applied in everyday clinical physiotherapy practice. However, the results suggested considering the IKDC as one component of an evaluation kit to make decisions regarding the progress of the rehabilitation treatment.

The importance of total kidney volume in evaluating progression of polycystic kidney disease

PubMed Central

Grantham, Jared J.; Torres, Vicente E.

2017-01-01

The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue. PMID:27694979

Assessment of Individuals with Primary Progressive Aphasia.

PubMed

Henry, Maya L; Grasso, Stephanie M

2018-07-01

Speech-language pathologists play a crucial role in the assessment and treatment of individuals with primary progressive aphasia (PPA). The speech-language evaluation is a critical aspect of the diagnostic and rehabilitative process, informing differential diagnosis as well as intervention planning and monitoring of cognitive-linguistic status over time. The evaluation should include a thorough case history and interview and a detailed assessment of speech-language and cognitive functions, with tasks designed to detect core and associated deficits outlined in current diagnostic criteria. In this paper, we review assessments that can be utilized to examine communication and cognition in PPA, including general aphasia batteries designed for stroke and/or progressive aphasia as well as tests of specific cognitive-linguistic functions, including naming, object/person knowledge, single-word and sentence comprehension, repetition, spontaneous speech/language production, motor speech, written language, and nonlinguistic cognitive domains. The comprehensive evaluation can inform diagnostic decision making and facilitate planning of interventions that are tailored to the patient's current status and likely progression of deficits. As such, the speech-language evaluation allows the medical team to provide individuals with PPA and their families with appropriate recommendations for the present and the future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

PubMed

García-Gutiérrez, Valentin; Puerta, Jose Manuel; Maestro, Begoña; Casado Montero, Luis Felipe; Muriel, Alfonso; Molina Hurtado, Jose Ramon; Perez-Encinas, Manuel; Moreno Romero, Maria Victoria; Suñol, Pere Barba; Sola Garcia, Ricardo; De Paz, Raquel; Ramirez Sanchez, Maria Jose; Osorio, Santiago; Mata Vazquez, Maria Isabel; Martinez López, Joaquin; Sastre, Jose Luis; Portero, Maria de Los Angles; Bautista, Guiomar; Duran Nieto, Maria Soledad; Giraldo, Pilar; Jimenez Jambrina, Margarita; Burgaleta, Carmen; Ruiz Aredondo, Joaquin; Peñarrubia, Maria Jesús; Requena, Maria José; Fernández Valle, María Del Carmen; Calle, Carmen; Paz Coll, Antonio; Hernández-Rivas, Jose Ángel; Franco Osorio, Rafael; Cano, Pilar; Tallón Pérez, David; Fernández de la Mata, Margarita; Garrido, Pilar López; Steegmann, Juan Luis

2014-11-01

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival. © 2014 Wiley Periodicals, Inc.

Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo.

PubMed

Gleissman, Helena; Segerström, Lova; Hamberg, Mats; Ponthan, Frida; Lindskog, Magnus; Johnsen, John Inge; Kogner, Per

2011-04-01

Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma. Copyright © 2010 UICC.

What is the added value of ultrasound joint examination for monitoring synovitis in rheumatoid arthritis and can it be used to guide treatment decisions? A systematic review and cost-effectiveness analysis.

PubMed

Simpson, Emma; Hock, Emma; Stevenson, Matt; Wong, Ruth; Dracup, Naila; Wailoo, Allan; Conaghan, Philip; Estrach, Cristina; Edwards, Christopher; Wakefield, Richard

2018-04-01

Synovitis (inflamed joint synovial lining) in rheumatoid arthritis (RA) can be assessed by clinical examination (CE) or ultrasound (US). To investigate the added value of US, compared with CE alone, in RA synovitis in terms of clinical effectiveness and cost-effectiveness. Electronic databases including MEDLINE, EMBASE and the Cochrane databases were searched from inception to October 2015. A systematic review sought RA studies that compared additional US with CE. Heterogeneity of the studies with regard to interventions, comparators and outcomes precluded meta-analyses. Systematic searches for studies of cost-effectiveness and US and treatment-tapering studies (not necessarily including US) were undertaken. A model was constructed that estimated, for patients in whom drug tapering was considered, the reduction in costs of disease-modifying anti-rheumatic drugs (DMARDs) and serious infections at which the addition of US had a cost per quality-adjusted life-year (QALY) gained of £20,000 and £30,000. Furthermore, the reduction in the costs of DMARDs at which US becomes cost neutral was also estimated. For patients in whom dose escalation was being considered, the reduction in number of patients escalating treatment and in serious infections at which the addition of US had a cost per QALY gained of £20,000 and £30,000 was estimated. The reduction in number of patients escalating treatment for US to become cost neutral was also estimated. Fifty-eight studies were included. Two randomised controlled trials compared adding US to a Disease Activity Score (DAS)-based treat-to-target strategy for early RA patients. The addition of power Doppler ultrasound (PDUS) to a Disease Activity Score 28 joints-based treat-to-target strategy in the Targeting Synovitis in Early Rheumatoid Arthritis (TaSER) trial resulted in no significant between-group difference for change in Disease Activity Score 44 joints (DAS44). This study found that significantly more patients in the PDUS group attained DAS44 remission ( p  = 0.03). The Aiming for Remission in Rheumatoid Arthritis (ARCTIC) trial found that the addition of PDUS and grey-scale ultrasound (GSUS) to a DAS-based strategy did not produce a significant between-group difference in the primary end point: composite DAS of < 1.6, no swollen joints and no progression in van der Heijde-modified total Sharp score (vdHSS). The ARCTIC trial did find that the erosion score of the vdHS had a significant advantage for the US group ( p  = 0.04). In the TaSER trial there was no significant group difference for erosion. Other studies suggested that PDUS was significantly associated with radiographic progression and that US had added value for wrist and hand joints rather than foot and ankle joints. Heterogeneity between trials made conclusions uncertain. No studies were identified that reported the cost-effectiveness of US in monitoring synovitis. The model estimated that an average reduction of 2.5% in the costs of biological DMARDs would be sufficient to offset the costs of 3-monthly US. The money could not be recouped if oral methotrexate was the only drug used. Heterogeneity of the trials precluded meta-analysis. Therefore, no summary estimates of effect were available. Additional costs and health-related quality of life decrements, relating to a flare following tapering or disease progression, have not been included. The feasibility of increased US monitoring has not been assessed. Limited evidence suggests that US monitoring of synovitis could provide a cost-effective approach to selecting RA patients for treatment tapering or escalation avoidance. Considerable uncertainty exists for all conclusions. Future research priorities include evaluating US monitoring of RA synovitis in longitudinal clinical studies. This study is registered as PROSPERO CRD42015017216. The National Institute for Health Research Health Technology Assessment programme.

The Reliability and Validity of a Progress-Monitoring Tool: A Psychometric Examination of the Phonological Awareness Skills of Preschoolers with ASD

ERIC Educational Resources Information Center

Martini, Jay R.

2017-01-01

The purpose of this study was to conduct a psychometric evaluation the "Sound Beginning" phonological awareness progress monitoring tool. This assessment was used to track emergent literacy skills of preschoolers with autism spectrum disorder who were participating in a randomized trial studying early literacy interventions. Research…

Technical Adequacy of Growth Estimates from a Computer Adaptive Test: Implications for Progress Monitoring

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Nelson, Peter M.; Parker, David C.

2017-01-01

Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data…

Using Parents and Teachers to Monitor Progress among Children with ASD: A Review of Intervention Research

ERIC Educational Resources Information Center

Witmer, Sara E.; Nasamran, Amy; Parikh, Purvi J.; Schmitt, Heather A.; Clinton, Marianne C.

2015-01-01

Despite growing knowledge of the effectiveness of various interventions for children with autism spectrum disorders (ASD), it is never clear whether a particular intervention will be effective for a specific child with ASD. Careful monitoring of an individual child's progress is necessary to know whether an intervention is effective. In this…

Technical Adequacy of Early Numeracy Curriculum-Based Progress Monitoring Measures for Kindergarten and First-Grade Students

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.; Lee, Young-Sun; Pappas, Sandra; Chiong, Cynthia; Ginsburg, Herbert P.

2012-01-01

The purpose of this study was to examine six early numeracy measures used to monitor the mathematics progress of kindergarten and first-grade students. Seventy-one kindergarten students and 75 first-grade students were administered the measures each week. Delayed-alternate form reliability was adequate for instructional decision making on some…

Curriculum-Based Measurement of Reading: Is 6 Weeks of Daily Progress Monitoring Enough?

ERIC Educational Resources Information Center

Thornblad, Shannon C.; Christ, Theodore J.

2014-01-01

Curriculum-based measurement of reading (CBM-R) is used in research and practice to estimate the level and trend of student achievement. Although there is limited empirical or psychometric support to guide CBM-R progress monitoring practices, derived trend estimates are used to inform a variety of educational decisions including evaluations of…

Curriculum-Based Measurement of Reading Progress Monitoring: The Importance of Growth Magnitude and Goal Setting in Decision Making

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Christ, Theodore J.; Newell, Kirsten W.

2017-01-01

Research regarding the technical adequacy of growth estimates from curriculum-based measurement of reading progress monitoring data suggests that current decision-making frameworks are likely to yield inaccurate recommendations unless data are collected for extensive periods of time. Instances where data may not need to be collected for long…

Curriculum-Based Measurement of Oral Reading: A Preliminary Investigation of Confidence Interval Overlap to Detect Reliable Growth

ERIC Educational Resources Information Center

Van Norman, Ethan R.

2016-01-01

Curriculum-based measurement of oral reading (CBM-R) progress monitoring data is used to measure student response to instruction. Federal legislation permits educators to use CBM-R progress monitoring data as a basis for determining the presence of specific learning disabilities. However, decision making frameworks originally developed for CBM-R…

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

NASA Astrophysics Data System (ADS)

Waller, J. M.; Andrade, E.; Saulsberry, R. L.

2010-02-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Explaining engagement in self-monitoring among participants of the DESMOND Self-monitoring Trial: a qualitative interview study

PubMed Central

Eborall, Helen C; Dallosso, Helen M; McNicol, Sarah; Speight, Jane; Khunti, Kamlesh; Davies, Melanie J; Heller, Simon R

2015-01-01

Abstract Background. The Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) Self-monitoring Trial reported that people with newly diagnosed type 2 diabetes attending community-based structured education and randomized to self-monitoring of blood glucose (SMBG) or urine monitoring had comparable improvements in biomedical outcomes, but differences in satisfaction with, and continued use of monitoring method, well-being and perceived threat from diabetes. Objectives. To explore experiences of SMBG and urine monitoring following structured education. We specifically addressed the perceived usefulness of each monitoring method and the associated well-being. Methods. Qualitative semi-structured interviews with 18 adults with newly diagnosed type 2 diabetes participating in the DESMOND Self-monitoring Trial (SMBG, N = 10; urine monitoring, N = 8) ~12 months into the trial. Analysis was informed by the constant comparative approach. Results. Interviewees reported SMBG as accurate, convenient and useful. Declining use was explained by having established a pattern of managing blood glucose with less frequent monitoring or lack of feedback or encouragement from health care professionals. Many initially positive views of urine monitoring progressively changed due to perceived inaccuracy, leading some to switch to SMBG. Perceiving diabetes as less serious was attributable to lack of symptoms, treatment with diet alone and—in the urine-monitoring group—consistently negative readings. Urine monitoring also provided less visible evidence of diabetes and of the effect of behaviour on glucose. Conclusions. The findings highlight the importance for professionals of considering patients’ preferences when using self-monitoring technologies, including how these change over time, when supporting the self-care behaviours of people with type 2 diabetes. PMID:26160892

Transient Asymptomatic Pulmonary Opacities Occurring during Osimertinib Treatment.

PubMed

Noonan, Sinead A; Sachs, Peter B; Camidge, D Ross

2016-12-01

Osimertinib is an EGFR inhibitor licensed for the treatment of EGFR-mutant, T790M-positive NSCLC. Previously unreported, frequent transient asymptomatic pulmonary opacities were noted in patients during osimertinib therapy at the University of Colorado. Computed tomography imaging and clinical notes on patients with NSCLC who had been treated with osimertinib at the University of Colorado were retrospectively reviewed. Transient asymptomatic pulmonary opacities developed in seven of 20 patients (35%) while they were receiving osimertinib. The radiological patterns seen included ground-glass opacities with or without nodular consolidation. The median time to development of the first lesion was 8.7 weeks (range 1.6-43 weeks), the median time to resolution during continued osimertinib was 6 weeks (range 1-11 weeks). Transient asymptomatic pulmonary opacities may be a previously unrecognized, benign feature associated with osimertinib therapy that may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new-onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic and localized and there is no evidence of disease progression elsewhere, it may be reasonable to continue treatment with osimertinib and monitor the lesions for resolution. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression

PubMed Central

Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E.; Joshi, Virendra; Salomon, Carlos

2017-01-01

Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (∼150-1000 nm) and exosomes (∼40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a fingerprint of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression. PMID:27999198

Glycemic control in diabetes in three Danish counties.

PubMed

Jørgensen, Lone G M; Petersen, Per Hyltoft; Heickendorff, Lene; Møller, Holger Jon; Hendel, Jørn; Christensen, Cramer; Schmitz, Anita; Reinholdt, Birgitte; Lund, Erik D; Christensen, Niels J; Hansen, Erik Kjaersgaard; Hastrup, Jens; Skjødt, Hanne; Eriksen, Ebbe Wendel; Brandslund, Ivan

2005-01-01

Hemoglobin A1c (HbA1c) is a proxy measure for glycemic control in diabetes. We investigated the trend for glycemic control in patients from three Danish counties using HbA1c measurements. We studied 2454 patients from a population of 807,000 inhabitants for whom routine monitoring of diabetes using HbA1c-DCCT aligned was initiated in 2001. We estimated the incidence of monitored patients in the population. The progress in patients with originally diabetic HbA1c levels was investigated by cumulative probability plots, and the individual trend in clinical outcome was investigated by a modified difference plot. The age-standardized incidence of monitored patients was <0.5% in all regions. Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. The overall percentage above the treatment target (>or=6.62% HbA1c) was 51% in 2003 compared to 59% in 2001, and the percentage with poor glycemic control (>or=10.0% HbA1c) was reduced from 19% to 4%. Of patients with originally diabetic HbA1c levels, 15% showed progress in glycemic control, and 28% reached treatment targets. In patients with originally normal HbA1c, 75% showed an upward trend in HbA1c levels, which reached diabetic concentrations in 17%. Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. In individual patients, 75% with originally diabetic HbA1c levels showed improved glycemic control after 3 years, while 78% with originally normal concentrations showed an upward trend in HbA1c levels.

Quantitative head ultrasound measurements to determine thresholds for preterm neonates requiring interventional therapies following intraventricular hemorrhage

NASA Astrophysics Data System (ADS)

Kishimoto, Jessica; Fenster, Aaron; Salehi, Fateme; Romano, Walter; Lee, David S. C.; de Ribaupierre, Sandrine

2016-04-01

Dilation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage (IVH). This post hemorrhagic ventricle dilation (PHVD) can lead to lifelong neurological impairment through ischemic injury due to increased intracranial pressure and without treatment, can lead to death. Clinically, 2D ultrasound (US) through the fontanelles ('soft spots') of the patients are serially acquired to monitor the progression of the ventricle dilation. These images are used to determine when interventional therapies such as needle aspiration of the built up cerebrospinal fluid (CSF) ('ventricle tap', VT) might be indicated for a patient; however, quantitative measurements of the growth of the ventricles are often not performed. There is no consensus on when a neonate with PHVD should have an intervention and often interventions are performed after the potential for brain damage is quite high. Previously we have developed and validated a 3D US system to monitor the progression of ventricle volumes (VV) in IVH patients. We will describe the potential utility of quantitative 2D and 3D US to monitor and manage PHVD in neonates. Specifically, we will look to determine image-based measurement thresholds for patients who will require VT in comparison to patients with PHVD who resolve without intervention. Additionally, since many patients who have an initial VT will require subsequent interventions, we look at the potential for US to determine which PHVD patients will require additional VT after the initial one has been performed.

Crystal digital droplet PCR for detection and quantification of circulating EGFR sensitizing and resistance mutations in advanced non-small cell lung cancer

PubMed Central

Madic, Jordan; Remon, Jordi; Honoré, Aurélie; Girard, Romain; Rouleau, Etienne; André, Barbara; Besse, Benjamin; Droniou, Magali; Lacroix, Ludovic

2017-01-01

Over the past years, targeted therapies using tyrosine kinase inhibitors (TKI) have led to an increase in progression-free survival and response rate for a subgroup of non-small cell lung cancer (NSCLC) patients harbouring specific gene abnormalities compared with chemotherapy. However long-lasting tumor regression is rarely achieved, due to the development of resistant tumoral subclones, which requires alternative therapeutic approaches. Molecular profile at progressive disease is a challenge for making adaptive treatment decisions. The aim of this study was to monitor EGFR-mutant tumors over time based on the quantity of mutant DNA circulating in plasma (ctDNA), comparing two different methods, Crystal™ Digital™ PCR and Massive Parallel Sequencing (MPS). In plasma circulating cell free DNA (cfDNA) of 61 advanced NSCLC patients we found an overall correlation of 78% between mutated allelic fraction measured by Crystal Digital PCR and MPS. 7 additional samples with sensitizing mutations and 4 additional samples with the resistance mutation were detected with Crystal Digital PCR, but not with MPS. Monitoring levels of both mutation types over time showed a correlation between levels and trends of mutated ctDNA detected and clinical assessment of disease for the 6 patients tested. In conclusion, Crystal Digital PCR exhibited good performance for monitoring mutational status in plasma cfDNA, and also appeared as better suited to the detection of known mutations than MPS in terms of features such as time to results. PMID:28829811

Progress and Compliance in Alcohol Abuse Treatment*

PubMed Central

Lien, Hsien-Ming; Lu, Mingshan; Ma, Ching-To Albert; McGuire, Thomas G.

2009-01-01

Improving patient compliance with physicians’ treatment or prescription recommendations is an important goal in medical practice. We examine the relationship between treatment progress and patient compliance. We hypothesize that patients balance expected benefits and costs during a treatment episode when deciding on compliance; a patient is more likely to comply if doing so results in an expected gain in health benefit. We use a unique data set of outpatient alcohol abuse treatment to identify a relationship between treatment progress and compliance. Treatment progress is measured by the clinician’s comments after each attended visit. Compliance is measured by a client attending a scheduled appointment, and continuing with treatment. We find that a patient who is making progress is less likely to drop out of treatment. We find no evidence that treatment progress raises the likelihood of a patient attending the next scheduled visit. Our results are robust to unobserved patient heterogeneity. PMID:20031241

Wavelength-dependent backscattering measurements for quantitative real-time monitoring of apoptosis in living cells

NASA Astrophysics Data System (ADS)

Mulvey, Christine S.; Sherwood, Carly A.; Bigio, Irving J.

2009-11-01

Apoptosis-programmed cell death-is a cellular process exhibiting distinct biochemical and morphological changes. An understanding of the early morphological changes that a cell undergoes during apoptosis can provide the opportunity to monitor apoptosis in tissue, yielding diagnostic and prognostic information. There is avid interest regarding the involvement of apoptosis in cancer. The initial response of a tumor to successful cancer treatment is often massive apoptosis. Current apoptosis detection methods require cell culture disruption. Our aim is to develop a nondisruptive optical method to monitor apoptosis in living cells and tissues. This would allow for real-time evaluation of apoptotic progression of the same cell culture over time without alteration. Elastic scattering spectroscopy (ESS) is used to monitor changes in light-scattering properties of cells in vitro due to apoptotic morphology changes. We develop a simple instrument capable of wavelength-resolved ESS measurements from cell cultures in the backward direction. Using Mie theory, we also develop an algorithm that extracts the size distribution of scatterers in the sample. The instrument and algorithm are validated with microsphere suspensions. For cell studies, Chinese hamster ovary (CHO) cells are cultured to confluence on plates and are rendered apoptotic with staurosporine. Backscattering measurements are performed on pairs of treated and control samples at a sequence of times up to 6-h post-treatment. Initial results indicate that ESS is capable of discriminating between treated and control samples as early as 10- to 15-min post-treatment, much earlier than is sensed by standard assays for apoptosis. Extracted size distributions from treated and control samples show a decrease in Rayleigh and 150-nm scatterers, relative to control samples, with a corresponding increase in 200-nm particles. Work continues to correlate these size distributions with underlying morphology. To our knowledge, this is the first report of the use of backscattering spectral measurements to quantitatively monitor apoptosis in viable cell cultures in vitro.

The potential role of brain asymmetry in the development of adolescent idiopathic scoliosis: a hypothesis.

PubMed

Niesluchowski, W; Dabrowska, A; Kedzior, K; Zagrajek, T

1999-10-01

The size asymmetry of cerebral hemispheres may predispose to head tilt and asymmetric blocking of the zygapophysial joints, potentially leading to the development of compensatory curvatures in the lower segments of the spine. To analyze the effects of spinal manipulation, maintained by an exercise program, on the progression of idiopathic adolescent scoliosis in 2 children aged 6 and 10. The scoliosis found was 16 and 60 degrees. For diagnosis and monitoring of therapy, we recorded qualitative parameters of shoulder asymmetry, axillary line asymmetry, and scapular angle position. Manual treatment consisted of the examinations of all sliding motion in zygapophysial joints and both sacroiliac joints and removing the limitations of the sliding motions according to the method of Karel Lewit. The treatment procedure consisted of 3 or 4 manipulations within 17 months and an exercise program. The manipulation effects were maintained by the exercise program. The exercises were done in 2 or 3 sessions weekly for a year. In both patients we observed that scoliosis decompensation was successfully stopped and the effects of the correction persisted for 10 years. Brain and head asymmetry may be only a transient state, predisposing to asymmetric blocking at the atlanto-occipital level. Removal of blocking may prevent curve progression in children who had adolescent idiopathic scoliosis. The manipulative therapy may also have a promising effect on retarding curve progression when used in skeletally immature patient.

Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

PubMed

Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

2013-05-01

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

Variations in the endogenous fluorescence of rabbit corneas after mechanical property alterations

NASA Astrophysics Data System (ADS)

Ortega-Martinez, Antonio; Touchette, Genna; Zhu, Hong; Kochevar, Irene E.; Franco, Walfre

2017-09-01

Keratoconus is an eye disease in which the cornea progressively deforms due to loss of cornea mechanical rigidity, and thus causes deterioration of visual acuity. Techniques to characterize the mechanical characteristics of the cornea are important to better monitor changes and response to treatments. To investigate the feasibility of using the endogenous fluorescence of cornea for monitoring alterations of its mechanical rigidity, linear tensiometry was used to quantitate stiffness and Young's modulus (YM) after treatments that increase cornea stiffness (collagen photocross-linking) or decrease stiffness (enzymatic digestion). The endogenous ultraviolet fluorescence of cornea was also measured before and after these treatments. The fluorescence excitation/emission spectral ranges were 280 to 430/390 to 520 nm, respectively. A correlation analysis was carried out to identify fluorescence excitation/emission pairs whose intensity changes correlated with the stiffness. A positive correlation was found between variations in fluorescence intensity of the 415-/485-nm excitation/emission pair and YM of photocross-linked corneas. After treatment of corneas with pepsin, the YM decreased as the fluorescence intensity at 290-/390-nm wavelengths decreased. For weakening of corneas with collagenase, only qualitative changes in the fluorescence spectrum were observed. Changes in the concentration of native or newly created fluorescent molecular species contain information that may be directly or indirectly related to the mechanical structure of the cornea.

Development and psychometrics of the five item daily index in a psychiatric sample.

PubMed

Dyer, Kale; Hooke, Geoff; Page, Andrew C

2014-01-01

Effective treatment of affective disorders requires the ability to reliably monitor patient progress and outcome. The current study aimed to establish the Daily Index-5 (DI-5) as a psychometrically sound and clinically valid measure of treatment response in psychiatric care for use as a companion measure with the WHO Wellbeing Index (WHO-5; Bech et al., 1996. Psychother. Psychosom. 65, 183-190.). Eight hundred and ninety four consecutive inpatients and day-patients at a psychiatric facility completed the DI-5, WHO-5, SF-36 (Ware et al., 1993. SF-36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, MA.) and DASS-21 (Lovibond and Lovibond, 1995b. Manual for the Depression Anxiety Stress Scales. Psychology Foundation, Sydney, Australia.; Ware et al., 1993. SF-36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, MA.) routinely during treatment. The DI-5 was shown to be a measure with high reliability and validity. In addition criteria for clinically significant recovery are presented with an example implementation of a Clinical Significance Monitoring system. Finally, the latent structure of the DI-5 is established as a uni-dimensional index of affective disorder. The results may be generalized to samples with primary diagnoses of depressive and/or anxiety disorders though assessment of the DI-5 as a measure of treatment response is warranted in patients with other primary diagnoses. The current study indicates that the DI-5 is a quick to administer and interpret, reliable and valid measure for assessing patient outcome that is appropriate for use in monitoring patient change. © 2013 Published by Elsevier B.V.

The translocator protein radioligand 18F-DPA-714 monitors antitumor effect of erufosine in a rat 9L intracranial glioma model.

PubMed

Awde, Ali R; Boisgard, Raphaël; Thézé, Benoit; Dubois, Albertine; Zheng, Jinzi; Dollé, Frédéric; Jacobs, Andreas H; Tavitian, Bertrand; Winkeler, Alexandra

2013-12-01

On the one hand, the translocator protein (TSPO) radioligand N,N-diethyl-2-(2-(4-(2-(18)F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ((18)F-DPA-714) has been suggested to serve as an alternative radiotracer to image human glioma, and on the other hand the alkylphosphocholine erufosine (ErPC3) has been reported to induce apoptosis in otherwise highly apoptosis-resistant glioma cell lines. The induction of apoptosis by ErPC3 requires TSPO, a mitochondrial membrane protein highly expressed in malignant gliomas. In this preclinical study, we monitored the effect of ErPC3 treatment in vivo using (18)F-DPA-714 PET. In vitro studies investigated the antitumor effect of ErPC3 in 9L rat gliosarcoma cells. In vivo, glioma-bearing rats were imaged with (18)F-DPA-714 for the time of treatment. A significant decrease in 9L cell proliferation and viability and a significant increase in apoptosis and caspase-3 activation were demonstrated on ErPC3 treatment in cell culture. In the rat model, ErPC3 administration resulted in significant changes in (18)F-DPA-714 tumor uptake over the course of the treatment. Immunohistochemistry revealed reduced tumor volume and increased cell death in ErPC3-treated animals accompanied by infiltration of the tumor core by CD11b-positive microglia/macrophages and glial fibrillary acidic protein-positive astrocytes. Our findings demonstrate a potent antitumor effect of ErPC3 in vitro, in vivo, and ex vivo. PET imaging of TSPO expression using (18)F-DPA-714 allows effective monitoring and quantification of disease progression and response to ErPC3 therapy in intracranial 9L gliomas.

Test Review: Mather, N., Hammill, D. D., Allen, E. A., & Roberts, R. (2004). "Test of Silent Word Reading Fluency." Austin, TX: PRO-ED

ERIC Educational Resources Information Center

Williams, Ashley; Bell, Sherry Mee

2005-01-01

With the recently passed Individuals with Disabilities Education Act (2004), federal law encourages monitoring student progress and gauging responsiveness to instruction. The Test of Silent Word Reading Fluency (TOSWRF; Mather, Hammill, Allen, & Roberts, 2004) is a group-administered test that holds promise for monitoring student progress.…

Progress Monitoring Change in Children's Social, Emotional, and Behavioral Functioning: Advancing the State of the Science

ERIC Educational Resources Information Center

Owens, Julie Sarno; Evans, Steven W.

2018-01-01

The studies in this special series examine the effectiveness of direct behavior ratings (DBRs) for use as a progress monitoring tool. In this article, we comment on the findings of the studies in the context of the broader school-based assessment movement and discuss areas for future inquiry within this line of research.

Curriculum-Based Measurement of Reading: An Evaluation of Frequentist and Bayesian Methods to Model Progress Monitoring Data

ERIC Educational Resources Information Center

Christ, Theodore J.; Desjardins, Christopher David

2018-01-01

Curriculum-Based Measurement of Oral Reading (CBM-R) is often used to monitor student progress and guide educational decisions. Ordinary least squares regression (OLSR) is the most widely used method to estimate the slope, or rate of improvement (ROI), even though published research demonstrates OLSR's lack of validity and reliability, and…

Curriculum-Based Measurement: Developing a Computer-Based Assessment Instrument for Monitoring Student Reading Progress on Multiple Indicators

ERIC Educational Resources Information Center

Forster, Natalie; Souvignier, Elmar

2011-01-01

The purpose of this study was to examine the technical adequacy of a computer-based assessment instrument which is based on hierarchical models of text comprehension for monitoring student reading progress following the Curriculum-Based Measurement (CBM) approach. At intervals of two weeks, 120 third-grade students finished eight CBM tests. To…

The Effects of Baseline Estimation on the Reliability, Validity, and Precision of CBM-R Growth Estimates

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Christ, Theodore J.; Zopluoglu, Cengiz

2013-01-01

This study examined the effect of baseline estimation on the quality of trend estimates derived from Curriculum Based Measurement of Oral Reading (CBM-R) progress monitoring data. The authors used a linear mixed effects regression (LMER) model to simulate progress monitoring data for schedules ranging from 6-20 weeks for datasets with high and low…

Growth on Oral Reading Fluency Measures as a Function of Special Education and Measurement Sufficiency

ERIC Educational Resources Information Center

Tindal, Gerald; Nese, Joseph F. T.; Stevens, Joseph J.; Alonzo, Julie

2016-01-01

For 30 years, researchers have investigated oral reading fluency as a measure of growth in reading proficiency. Yet, little research has been done with these measures in the context of progress monitoring in Tier 2 systems. First, we document teachers' progress-monitoring decisions on type of passage (on-grade or off-grade) and how often to…

Using Curriculum Based Measures To Identify and Monitor Progress in an Adult Basic Education Program. Final Report.

ERIC Educational Resources Information Center

Bean, Rita M.; And Others

The purpose of a project was to develop and test curriculum-based procedures and measures to monitor and assess the reading and writing progress of adults in a basic education program. The most efficient, reliable, and feasible measure of reading performance from beginning reading level through eighth-grade level was the repeated oral reading…

HIV policy and implementation: a national policy review and an implementation case study of a rural area of northern Malawi.

PubMed

Dasgupta, Aisha N Z; Wringe, Alison; Crampin, Amelia C; Chisambo, Christina; Koole, Olivier; Makombe, Simon; Sungani, Charles; Todd, Jim; Church, Kathryn

2016-09-01

Malawi is a global leader in the design and implementation of progressive HIV policies. However, there continues to be substantial attrition of people living with HIV across the "cascade" of HIV services from diagnosis to treatment, and program outcomes could improve further. Ability to successfully implement national HIV policy, especially in rural areas, may have an impact on consistency of service uptake. We reviewed Malawian policies and guidelines published between 2003 and 2013 relating to accessibility of adult HIV testing, prevention of mother-to-child transmission and HIV care and treatment services using a policy extraction tool, with gaps completed through key informant interviews. A health facility survey was conducted in six facilities serving the population of a demographic surveillance site in rural northern Malawi to investigate service-level policy implementation. Survey data were analyzed using descriptive statistics. Policy implementation was assessed by comparing policy content and facility practice using pre-defined indicators covering service access: quality of care, service coordination and patient tracking, patient support, and medical management. ART was rolled out in Malawi in 2004 and became available in the study area in 2005. In most areas, practices in the surveyed health facilities complied with or exceeded national policy, including those designed to promote rapid initiation onto treatment, such as free services and task-shifting for treatment initiation. However, policy and/or practice were/was lacking in certain areas, in particular those strategies to promote retention in HIV care (e.g., adherence monitoring and home-based care). In some instances, though, facilities implemented alternative progressive practices aimed at improving quality of care and encouraging adherence. While Malawi has formulated a range of progressive policies aiming to promote rapid initiation onto ART, increased investment in policy implementation strategies and quality service delivery, in particular to promote long-term retention on treatment may improve outcomes further.

2016 Nebraska Higher Education Progress Report

ERIC Educational Resources Information Center

Nebraska's Coordinating Commission for Postsecondary Education, 2016

2016-01-01

The 2016 Nebraska Higher Education Progress Report is the 12th annual progress report designed to provide the Nebraska Legislature with comparative statistics to monitor and evaluate progress toward achieving three key priorities for Nebraska's postsecondary education system. These priorities were developed by the 2003 LR 174 Higher Education Task…

Recognition and management of depression in skilled-nursing and long-term care settings: evolving targets for quality improvement.

PubMed

Boyle, Vicki L; Roychoudhury, Canopy; Beniak, Renee; Cohn, Lisa; Bayer, Albert; Katz, Ira

2004-01-01

Depression is a common disorder associated with suffering, morbidity, and mortality in nursing home residents. It is treatable, and improving the quality of treatment can have a major impact. MPRO, Michigan's Quality Improvement Organization, initiated a quality-improvement project in 14 nursing facilities to improve the accuracy of assessments, targeting, and monitoring of care. Electronic Minimum Data Set (MDS) data and medical-record abstraction results were combined to form the analytic dataset. Findings from the baseline phase demonstrated that, according to medical and administrative records, 26% of newly admitted nursing home residents had symptoms of depression that were apparent at admission, and an additional 12% were recognized early in their stay. Eighty-one percent of residents with depression were receiving treatment on admission to the facility, and 79% of those with depression recognized by Day 14 were treated by then. These data demonstrate progress toward improving the initiation of treatment for depression in nursing homes; however, there are still opportunities for improving the quality of care and, especially, the quality of assessments. The authors recommend the addition of the Geriatric Depression Scale to the federally mandated MDS for cognitively intact patients. There could also be mechanisms to ensure that providers and facilities follow recommended practice guidelines. Initiating treatment with antidepressant medications should be followed with monitoring of residents to identify those who still have depressive symptoms and to modify or intensify their treatment.

Fetal heart and uterine contraction monitor (image)

MedlinePlus

The fetal heart monitor and uterine contraction monitor provide a continuous record of the baby's heart rate and the mother's contraction rate as labor progresses. This device can provide early warning of fetal distress.

Efficacy and long-term outcome of gastritis therapy in cheetahs (Acinonyx jubatus).

PubMed

Citino, Scott B; Munson, Linda

2005-09-01

A prospective clinical trial evaluating efficacy and long-term outcome of treatments for lymphoplasmacytic gastritis in cheetahs (Acinonyx jubatus) was conducted. The study evaluated efficacy of 11 different antibiotic and antiinflammatory treatment protocols in 32 cheetahs (19 male, 13 female) for reducing gastric inflammation and Helicobacter colonization and monitored the course of disease through histologic grading of gastric biopsies. All cheetahs were biopsied up to I wk before treatment and then rebiopsied within 1 mo after treatment. Most animals were reassigned to a second treatment regimen within 6 mo. Each animal received from one to three treatments during the study period. After the trial, gastric biopsies were obtained from each cheetah annually until death or transfer from the facility to assess disease progression. The trial and follow-up period spanned 10 yr. At onset of the trial, all 32 cheetahs had some degree of gastritis, and 26 cheetahs (81%) were colonized with Helicobacter. Inflammatory lesions worsened regardless of treatment or the presence of Helicobacter. No treatment had a significant effect on inflammatory changes except the lansoprazole/clarithromycin/amoxicillin treatment group, which produced a short-term decrease in inflammation when compared to controls. Prednisone had no effect on gastric inflammation. Overall, 65% of colonized cheetahs were initially cleared of histologic evidence of Helicobacter by treatment, with short-term eradication occurring in 100% of the animals treated with omeprazole/clarithromycin/amoxicillin or tetracycline/metronidazole/Pepto-Bismol for 28 days. Long-term follow-up of treated animals in this study clearly demonstrated that these treatments had little effect on life-long progression of gastritis or on Helicobacter burden in individual cheetahs, although some treatments provided short-term reduction in gastritis and Helicobacter. These results provide evidence that Helicobacter alone is not the cause of gastritis in cheetahs and do not support the use of antibacterial treatments in cheetahs unless significant clinical signs (e.g., frequent vomiting/regurgitation, weight loss) are apparent.

Compilation of 1989 annual reports of the Navy ELF Communications System Ecological Monitoring Program. Volume 2. tabs C-F. Annual progress report, Jan-Dec 89

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

Not Available

1990-08-01

This is the eighth compilation of annual reports for the Navy's ELF Communications Systems Ecological Monitoring Program. The reports document the progress of eight studies performed during 1989 near the Naval Radio Transmitting Facility -- Republic, Michigan. The purpose of the monitoring is to determine whether electromagnetic fields produced by the ELF Communications System will affect resident biota or their ecological relationships. Soil Amoeba: Arthropoda and Earthworms: Pollinating Insects: Small Mammals and Nesting Birds.

Enhancement of the microbial community biomass and diversity during air sparging bioremediation of a soil highly contaminated with kerosene and BTEX.

PubMed

Kabelitz, Nadja; Machackova, Jirina; Imfeld, Gwenaël; Brennerova, Maria; Pieper, Dietmar H; Heipieper, Hermann J; Junca, Howard

2009-03-01

In order to obtain insights in complexity shifts taking place in natural microbial communities under strong selective pressure, soils from a former air force base in the Czech Republic, highly contaminated with jet fuel and at different stages of a bioremediation air sparging treatment, were analyzed. By tracking phospholipid fatty acids and 16S rRNA genes, a detailed monitoring of the changes in quantities and composition of the microbial communities developed at different stages of the bioventing treatment progress was performed. Depending on the length of the air sparging treatment that led to a significant reduction in the contamination level, we observed a clear shift in the soil microbial community being dominated by Pseudomonads under the harsh conditions of high aromatic contamination to a status of low aromatic concentrations, increased biomass content, and a complex composition with diverse bacterial taxonomical branches.

Brief Trauma and Mental Health Assessments for Female Offenders in Addiction Treatment

PubMed Central

Rowan-Szal, Grace A.; Joe, George W.; Bartholomew, Norma G; Pankow, Jennifer; Simpson, D. Dwayne

2012-01-01

Increasing numbers of women in prison raise concerns about gender-specific problems and needs severity. Female offenders report higher trauma as well as mental and medical health complications than males, but large inmate populations and limited resources create challenges in administering proper diagnostic screening and assessments. This study focuses on brief instruments that address specialized trauma and health problems, along with related psychosocial functioning. Women from two prison-based treatment programs for substance abuse were assessed (N = 1,397), including one facility for special needs and one for regular female offenders. Results affirmed that admissions to the special needs facility reported more posttraumatic stress symptoms, higher rates of psychological stress and previous hospitalizations, and more health issues than those in the regular treatment facility. Findings supporting use of these short forms and their applications as tools for monitoring needs, progress, and change over time are discussed. PMID:23087587

Adherence to oral cancer therapy in older adults: The International Society of Geriatric Oncology (SIOG) taskforce recommendations.

PubMed

Mislang, Anna Rachelle; Wildes, Tanya M; Kanesvaran, Ravindran; Baldini, Capucine; Holmes, Holly M; Nightingale, Ginah; Coolbrandt, Annemarie; Biganzoli, Laura

2017-06-01

There is an increasing trend towards using oral systemic therapy in patients with cancer. Compared to parenteral therapy, oral cancer agents offer convenience, have similar efficacy, and are preferred by patients, consequently making its use appealing in older adults. However, adherence is required to ensure its efficacy and to avoid compromising treatment outcomes, especially when the treatment goal is curative, or in case of symptomatic/rapidly progressing disease, where dose-intensity is important. This opens a new challenge for clinicians, as optimizing patient adherence is challenging, particularly due to lack of consensus and scarcity of available clinical evidence. This manuscript aims to review the impact of age-related factors on adherence, summarize the evidence on adherence, recommend methods for selecting patients suitable for oral cancer agents, and advise monitoring interventions to promote adherence to treatment. Copyright © 2017. Published by Elsevier Ltd.

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

2009-01-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

PubMed

Filippi, Luca; Cavallaro, Giacomo; Berti, Elettra; Padrini, Letizia; Araimo, Gabriella; Regiroli, Giulia; Bozzetti, Valentina; De Angelis, Chiara; Tagliabue, Paolo; Tomasini, Barbara; Buonocore, Giuseppe; Agosti, Massimo; Bossi, Angela; Chirico, Gaetano; Aversa, Salvatore; Pasqualetti, Roberta; Fortunato, Pina; Osnaghi, Silvia; Cavallotti, Barbara; Vanni, Maurizio; Borsari, Giulia; Donati, Simone; Nascimbeni, Giuseppe; la Marca, Giancarlo; Forni, Giulia; Milani, Silvano; Cortinovis, Ivan; Bagnoli, Paola; Dal Monte, Massimo; Calvani, Anna Maria; Pugi, Alessandra; Villamor, Eduardo; Donzelli, Gianpaolo; Mosca, Fabio

2017-07-14

Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Non operative management of cerebral abscess

NASA Astrophysics Data System (ADS)

Batubara, C. A.

2018-03-01

Cerebral abscess is a focal intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus surrounded by a well-vascularized capsule. Patients typically present with varying combinations of aheadache, progressive neurologic deficits, seizures, and evidence of infection. Computed Tomography and Magnetic Resonance Imagingare the most important diagnostic tools in diagnosing cerebral abscess. The treatment of cerebral abscess has been a challenge. Small cerebralabscesses (< 2.5 cm) have been treated empirically with antibiotics. Elevation of intracranial pressure and threatening herniation can be managed by the use of intravenous mannitol (or hypertonic saline) and dexamethasone. Acute seizures should be terminated with the administration of intravenous benzodiazepines or by intravenous fosphenytoin. Anticonvulsants prophylaxis must be initiated immediately and continued at least one year due to high risk in the cerebral abscesses. Easier detection of underlying conditions, monitoring of the therapeutic progress, and recognition of complications have probably contributed to the improved prognosis.

A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis.

PubMed Central

Lai, M; Hodgson, T; Gawne-Cain, M; Webb, S; MacManus, D; McDonald, W I; Thompson, A J; Miller, D H

1996-01-01

Long TR and gadolinium enhanced spin echo brain MRI was performed weekly for three months in three patients with relapsing-remitting or secondary progressive multiple sclerosis. During the study, 38 new enhancing lesions were seen; 11 showed enhancement for less than four weeks, and two enhanced on only one scan. All 16 new lesions seen on long TR scans showed initial enhancement. When only every fourth (monthly) scan was analysed, a total of 33 new enhancing lesions were seen. Subject to confirmation in a larger cohort, the results suggest: (a) that blood brain barrier leakage is an invariable event in new lesion development in relapsing-remitting and secondary progressive multiple sclerosis; (b) the small increase in sensitivity of weekly scanning does not justify its use in preference to monthly scanning when monitoring treatments. Images PMID:8609517

Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

PubMed Central

Nishimura, Toshihide; Kato, Harubumi; Ikeda, Norihiko; Kihara, Makoto; Nomura, Masaharu; Kato, Yasufumi; Marko-Varga, György

2012-01-01

An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care. PMID:22685658

Malawi's contribution to "3 by 5": achievements and challenges.

PubMed

Libamba, Edwin; Makombe, Simon D; Harries, Anthony D; Schouten, Erik J; Yu, Joseph Kwong-Leung; Pasulani, Olesi; Mhango, Eustice; Aberle-Grasse, John; Hochgesang, Mindy; Limbambala, Eddie; Lungu, Douglas

2007-02-01

Many resource-poor countries have started scaling up antiretroviral therapy (ART). While reports from individual clinics point to successful implementation, there is limited information about progress in government institutions at a national level. Malawi started national ART scale-up in 2004 using a structured approach. There is a focus on one generic, fixed-dose combination treatment with stavudine, lamivudine and nevirapine. Treatment is delivered free of charge to eligible patients with HIV and there is a standardized system for recruiting patients, monthly follow-up, registration, monitoring and reporting of cases and outcomes. All treatment sites receive quarterly supervision and evaluation. In January 2004, there were nine public sector facilities delivering ART to an estimated 4 000 patients. By December 2005, there were 60 public sector facilities providing free ART to 37,840 patients using national standardized systems. Analysis of quarterly cohort treatment outcomes at 12 months showed 80% of patients were alive, 10% dead, 9% lost to follow-up and 1% had stopped treatment. Achievements were the result of clear national ART guidelines, implementing partners working together, an intensive training schedule focused on clinical officers and nurses, a structured system of accrediting facilities for ART delivery, quarterly supervision and monitoring, and no stock-outs of antiretroviral drugs. The main challenges are to increase the numbers of children, pregnant women and patients with tuberculosis being started on ART, and to avert high early mortality and losses to follow-up. The capacity of the health sector to cope with escalating case loads and to scale up prevention alongside treatment will determine the future success of ART delivery in Malawi.

The effectiveness of choline citrate infusions monitored by lymphocyte transformation test (LTT) in multiple sclerosis. A new approach to the diagnosis and treatment of the disease.

PubMed

Muss, Claus; Stejskal, Vera; Titel, Ekkehard

2009-01-01

The efficacy of intravenous choline citrate infusions was investigated in 34 patients with multiple sclerosis (MS) by clinical evaluation and by monitoring of lymphocyte proliferation in vitro against fragments of myelin basic protein (MOG-35-55, MBP15-31, PLP 39-15) over a period of 12 weeks. Patients have been diagnosed with MS at least one year before entering the study and suffered from mild relapsing/remitting course to long-term chronic progressive disease. Twenty one patients exhibited positive lymphocyte proliferation to myelin fragments prior to treatment and were therefore selected for further studies. Choline citrate was administered with a dosage of 1200mg/ 2x week for a period of 3 months. This treatment resulted in a significant decrease of lymphocyte proliferation to neural fragments (MOG- 35-55, MBP15-31) in lymphocyte transformation test (LTT). There was no significant SI change of PLP Peptide (PLP 39-15) LTT found after treatment with choline citrate. During the 3 mo observation period, patients remained stable and no side-effects of the treatment were observed. In addition, some patients reported long-lasting improvement (less paresthesia and increase of muscle strength in lower extremities) which was demonstrated up to 3 years later. In one spectacular case a commercial pilot was able to return to duty again after treatment. This pilot was allowed back in to his position as a commercial flying cockpit member and is on duty for more than 4 yrs now.

[Aneurysm of the ascending aorta, hyperthyroidism and pregnancy. Case report].

PubMed

Zavala-Barrios, Berenice; García-Castanedo, Carla; Viruez-Soto, José Antonio; Briones-Garduño, Jesús Carlos; Coronel-Cruz, Fausto

2015-10-01

Aortic aneurysms are a rare condition in childhood and youth, etiology, evolution, natural progression and prognosis in pregnancy unknown. Hyperthyroidism occurs when there is a synthesis and/or excessive secretion of thyroid hormones during pregnancy poses difficulty for diagnosis. The new monitoring hemodynamics in pregnancy by transthoracic bioimpedance is a feasible alternative, noninvasive and real-time hemodynamic monitoring pregnant women. Primiparity 18, is referred to present tachycardia, hyperthyroidism is diagnosed and drug treatment is initiated with antithyroid from week 14.1 echocardiogram reports bivalve aortic aneurysm in the sinus of Valsalva is performed. He was determined to continue the same under strict hemodynamic and fetal monitoring. Pregnancy concludes at the end obtained through the abdomen, at 40.4 weeks, with male product, weight 2250 g, Apgar 9/9, with growth restriction type I. The mother and baby were discharged simultaneously without complications. The hyperdynamic state of pregnant patients in hyperthyroidism and aneurysms is complex and potentially complicable is why the hemodynamic patient monitoring is essential to detect changes in it that endanger the life of the binomial to this condition. Heart disease and hyperthyroidism, in this case, consistent with a fetal complications level is described as intrauterine growth restriction, however narrow and multidisciplinary monitoring and timely interventions binomial lead to satisfactory results in this case.

Examining the Technical Adequacy of Progress Monitoring Using Early Writing Curriculum-Based Measures

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.

2016-01-01

The purpose of this study was to examine 4 early writing measures used to monitor the early writing progress of 1st-grade students. We administered the measures to 23 1st-grade students biweekly for a total of 16 weeks. We obtained 3-min samples and conducted analyses for each 1-min increment. We scored samples using 2 different methods: correct…

The Use of Individual Growth and Developmental Indicators for Progress Monitoring and Intervention Decision Making in Early Education

ERIC Educational Resources Information Center

Walker, Dale; Carta, Judith J.; Greenwood, Charles R.; Buzhardt, Joseph F.

2008-01-01

Progress monitoring tools have been shown to be essential elements in current approaches to intervention problem-solving models. Such tools have been valuable not only in marking individual children's level of performance relative to peers but also in measuring change in skill level in a way that can be attributed to intervention and development.…

The Development and Technical Adequacy of Seventh-Grade Reading Comprehension Measures in a Progress Monitoring Assessment System. Technical Report #1102

ERIC Educational Resources Information Center

Park, Bitnara Jasmine; Alonzo, Julie; Tindal, Gerald

2011-01-01

This technical report describes the process of development and piloting of reading comprehension measures that are appropriate for seventh-grade students as part of an online progress screening and monitoring assessment system, http://easycbm.com. Each measure consists of an original fictional story of approximately 1,600 to 1,900 words with 20…

Monitoring Progress: How the 2012 National Survey of Science and Mathematics Education Can Inform a National K-12 STEM Education Indicator System

ERIC Educational Resources Information Center

Fulkerson, William O.; Banilower, Eric R.

2014-01-01

"Monitoring Progress Toward Successful K-12 STEM Education: A Nation Advancing?" (National Research Council, 2013) describes a set of 14 indicators for assessing and tracking the health of pre-college STEM education in the United States. This 2012 National Survey of Science and Mathematics Education (NSSME), is the fifth in a series of…

Optical profiling of anticoagulation status (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

2016-02-01

Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

Development of radon-222 as a natural tracer for monitoring the remediation of NAPL contamination in the subsurface. 1998 annual progress report

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

Semprini, L.; Istok, J.

'The objective of this research is to develop a unique method of using naturally occurring radon-222 as a tracer for locating and quantitatively describing the presence of subsurface NAPL contamination. The research will evaluate using radon as an inexpensive, yet highly accurate, means of detecting NAPL contamination and assessing the effectiveness of NAPL remediation. Laboratory, field, and modeling studies are being performed to evaluate this technique, and to develop methods for its successful implementation in practice. This report summarizes work that has been accomplished after 1-year of a 3-year project. The research to date has included radon tracer tests inmore » physical aquifer models (PAMs) and field studies at Site 300 of the Lawrence Livermore National Laboratory, CA, and Site 100D at Hanford DOE Facility, WA. The PAM tests have evaluated the ability of radon as a tracer to monitor the remediation of TCE NAPL contamination using surfactant treatment, and oxidation with permanganate. The surfactant tests were performed in collaboration with Dr. Jack Istok and Dr. Jennifer Field and their EMSP project ``In-situ, Field-Scale Evaluation of Surfactant Enhanced DNAPL Recovery Using a Single-Well-Push-Pull Test.'''' This collaboration enabled the EMSP radon project to make rapid progress. The PAM surfactant tests were performed in a radial flow geometry to simulate the push-pull-method that is being developed for surfactant field tests. The radon tests were easily incorporated into these experiments, since they simply rely on measuring the natural radon present in the subsurface fluids. Two types of radon tests were performed: (1) static tests where radon was permitted to build-up to steady-state concentrations in the pore fluids and the groundwater concentrations were monitored, and (2) dynamic tests were the radon response during push-pull surfactant tests was measured. Both methods were found to be useful in determining how NAPL remediation was progressing.'« less

Modelling the effect of wheat canopy architecture as affected by sowing density on Septoria tritici epidemics using a coupled epidemic–virtual plant model

PubMed Central

Baccar, Rim; Fournier, Christian; Dornbusch, Tino; Andrieu, Bruno; Gouache, David; Robert, Corinne

2011-01-01

Background and Aims The relationship between Septoria tritici, a splash-dispersed disease, and its host is complex because of the interactions between the dynamic plant architecture and the vertical progress of the disease. The aim of this study was to test the capacity of a coupled virtual wheat–Septoria tritici epidemic model (Septo3D) to simulate disease progress on the different leaf layers for contrasted sowing density treatments. Methods A field experiment was performed with winter wheat ‘Soissons’ grown at three contrasted densities. Plant architecture was characterized to parameterize the wheat model, and disease dynamic was monitored to compare with simulations. Three simulation scenarios, differing in the degree of detail with which plant variability of development was represented, were defined. Key Results Despite architectural differences between density treatments, few differences were found in disease progress; only the lower-density treatment resulted in a slightly higher rate of lesion development. Model predictions were consistent with field measurements but did not reproduce the higher rate of lesion progress in the low density. The canopy reconstruction scenario in which inter-plant variability was taken into account yielded the best agreement between measured and simulated epidemics. Simulations performed with the canopy represented by a population of the same average plant deviated strongly from the observations. Conclusions It was possible to compare the predicted and measured epidemics on detailed variables, supporting the hypothesis that the approach is able to provide new insights into the processes and plant traits that contribute to the epidemics. On the other hand, the complex and dynamic responses to sowing density made it difficult to test the model precisely and to disentangle the various aspects involved. This could be overcome by comparing more contrasted and/or simpler canopy architectures such as those resulting from quasi-isogenic lines differing by single architectural traits. PMID:21724656

Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer.

PubMed

Kaur, Paranjeet; Khatik, Gopal L

2016-01-01

Prostate cancer (PCa) is a leading cause of death in men worldwide. The main reason for the progression of prostate cancer is identified as over activation of androgen receptor (AR) through androgens. Its development can be diagnosed by monitoring the prostate specific antigen (PSA). Treatment of PCa includes prostatectomy, radiotherapy, and chemotherapy, among them chemotherapy is normally employed in early and advanced prostate cancer. Chemotherapy mainly includes two classes of drugs which are steroidal and non-steroidal antiandrogens. The non-steroidal classes of compounds are preferred over steroidal because they are relatively safe, cost effective and diverse. Non-steroidal drugs are commonly used for the treatment of PCa, however these drugs are associated with serious side effects and acquired resistance. So researchers are working in the direction to develop better analogue which can address the issue related to resistant type of prostate cancer. This review discusses the advancement in the non-steroidal antiandrogens which offers a better potential in the treatment of prostate cancer.

Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma.

PubMed

Cao, M González; Auge, J M; Molina, R; Martí, R; Carrera, C; Castel, T; Vilella, R; Conill, C; Sánchez, M; Malvehy, J; Puig, S

2007-01-01

Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.

Re-examining Nelson's syndrome.

PubMed

Palermo, Nadine E; Ananthakrishnan, Sonia

2015-08-01

Nelson's syndrome is a rare complication that can occur during the course of management of Cushing's disease. This article summarizes the recent literature on the diagnosis, monitoring and treatment of this potentially life-threatening outcome. Nelson's syndrome, with rising adrenocorticotropin hormone levels and corticotroph tumor progression on diagnostic imaging, can develop following treatment of refractory Cushing's disease with total bilateral adrenalectomy with/without radiotherapy. However, data showing that radiotherapy prevents Nelson's syndrome is inconsistent. In addition to the treatment of Nelson's syndrome with neurosurgery with/without adjuvant radiotherapy, selective somatostatin analogs and dopamine agonists, as well as other novel agents, have been used with increasing frequency in treating cases of Nelson's syndrome with limited benefit. The risk-benefit profile of each of these therapies is still not completely understood. Consensus guidelines on the evaluation and management of Nelson's syndrome are lacking. This article highlights areas in the surveillance of Cushing's disease patients, and diagnostic criteria and treatment regimens for Nelson's syndrome that require further research and review by experts in the field.

Chemically engineered persistent luminescence nanoprobes for bioimaging

PubMed Central

Lécuyer, Thomas; Teston, Eliott; Ramirez-Garcia, Gonzalo; Maldiney, Thomas; Viana, Bruno; Seguin, Johanne; Mignet, Nathalie; Scherman, Daniel; Richard, Cyrille

2016-01-01

Imaging nanoprobes are a group of nanosized agents developed for providing improved contrast for bioimaging. Among various imaging probes, optical sensors capable of following biological events or progresses at the cellular and molecular levels are actually actively developed for early detection, accurate diagnosis, and monitoring of the treatment of diseases. The optical activities of nanoprobes can be tuned on demand by chemists by engineering their composition, size and surface nature. This review will focus on researches devoted to the conception of nanoprobes with particular optical properties, called persistent luminescence, and their use as new powerful bioimaging agents in preclinical assays. PMID:27877248

Innate Lymphoid Cells in Tumor Immunity.

PubMed

van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

2016-02-25

Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

Contemporary retinal imaging techniques in diabetic retinopathy: a review.

PubMed

Cole, Emily Dawn; Novais, Eduardo Amorim; Louzada, Ricardo Noguera; Waheed, Nadia K

2016-05-01

Over the last decade, there has been an expansion of imaging modalities available to clinicians to diagnose and monitor the treatment and progression of diabetic retinopathy. Recently, advances in image technologies related to OCT and OCT angiography have enabled improved visualization and understanding of this disease. In this review, we will describe the use of imaging techniques such as colour fundus photography, fundus autofluorescence, fluorescein angiography, infrared reflectance imaging, OCT, OCT-Angiography and techniques in adaptive optics and hyperspectral imaging in the diagnosis and management of diabetic retinopathy. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Postacute Care in Cancer Rehabilitation.

PubMed

Guo, Ying; Fu, Jack B; Guo, Hong; Camp, Jennifer; Shin, Ki Y; Tu, Shi-Ming; Palmer, Lynn J; Yadav, Rajesh

2017-02-01

Acute care is usually associated with disease progression, treatments for cancer, and medical comorbidities. Patients with cancer may develop sudden functional deficits that require rehabilitation. Some of these patients benefit from acute rehabilitation, others benefit from subacute rehabilitation. After acute rehabilitation, continuous care for these patients has not been well described. Three studies are presented to demonstrate that cancer rehabilitation is a continuous process. Rehabilitation professionals should know how to detect fall risk, monitor symptoms, and render symptom management. Patients with cancer often require rehabilitation services during their entire disease trajectory. Copyright © 2016 Elsevier Inc. All rights reserved.

Innate Lymphoid Cells in Tumor Immunity

PubMed Central

van Beek, Jasper J. P.; Martens, Anne W. J.; Bakdash, Ghaith; de Vries, I. Jolanda M.

2016-01-01

Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring. PMID:28536374

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

ERIC Educational Resources Information Center

Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

2017-01-01

Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

Follow-up of IgD-κ multiple myeloma by monitoring free light chains and total heavy chain IgD: A case report

PubMed Central

De Santis, Elena; Masi, Serena; Cordone, Iole; Pisani, Francesco; Zuppi, Cecilia; Mattei, Fabrizio; Conti, Laura; Cigliana, Giovanni

2016-01-01

Immunoglobulin (Ig)D-κ multiple myeloma (MM) is a rare neoplastic disease characterized by an aggressive and rapidly progressing course, which constitutes only a very small proportion of all MM cases. In the present report, the clinical case of a 51-year-old Caucasian woman diagnosed with IgD-κ MM is described. The patient underwent different chemotherapeutic treatments subsequently to a single autologous stem cell transplantation. Despite the inherent difficulty of monitoring IgD levels and performing serum immunofixation electrophoresis, the clinical outcome of the patient was almost uniquely monitored by measuring the levels of κ and λ free light chains (FLCs) and total heavy chain IgD. The data suggest the non-invasive potential and usefulness of FLCs evaluation for early detection of stringent complete remission, follow-up and early detection of disease relapse. In addition, this diagnostic procedure has successfully been employed for the therapeutic monitoring of the present patient, and may represent a very helpful, non-invasive tool for the follow-up of IgD myeloma patients without the requirement of serial bone marrow aspirate. PMID:27588135

Non-pharmacological treatment of hypertension.

PubMed

Silverberg, D S

1990-09-01

Weight reduction, alcohol restriction, mild salt restriction, eating a vegetarian diet and increasing aerobic exercise will generally lower the blood pressure in patients with essential hypertension. Eating a diet rich in potassium and reducing caffeine intake may also be helpful in reducing the pressure, but increasing the fiber or calcium intake will generally be ineffective. Reducing fat intake from the usual 40% of total calories to 25-30% may reduce hypertension directly or by weight reduction. Smoking, when combined with excessive caffeine or alcohol intake may have an additive effect on blood pressure. Monotherapy with such behavioral techniques as self-monitoring of blood pressure, biofeedback, meditation, yoga, progressive muscular relaxation or cognitive therapy may reduce the blood pressure to a variable degree, and combinations of these treatments may be even more successful.

Reducing bone lead content by chelation treatment in chronic lead poisoning: an in vivo X-ray fluorescence and bone biopsy study

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

Batuman, V.; Wedeen, R.P.; Bogden, J.D.

1989-02-01

A stained-glass artist with longstanding exposure to lead presented with neuropsychiatric symptoms. He was evaluated before and after chelation treatment by the CaNa2 EDTA lead mobilization test, iliac crest bone lead measurement, and in vivo tibial X-ray fluorescence (XRF). The three methods showed a progressive fall in body lead stores during chelation therapy in association with improvement in symptoms and a fall in blood lead and zinc protoporphyrin levels. In vivo tibial XRF is a safe, rapid, and noninvasive technique for detecting excessive body lead burdens. XRF measurement of bone lead content is a practical method for monitoring the efficacymore » of therapy as well as for establishing the diagnosis.« less

Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

PubMed Central

Mermelstein, Joseph; Chait Mermelstein, Alanna; Chait, Maxwell M

2018-01-01

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. PMID:29606884

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.

What predicts the change from episodic to chronic migraine?

PubMed

Bigal, Marcelo E; Lipton, Richard B

2009-06-01

Because migraine worsens in a sizeable subgroup of sufferers, but not in most, identifying factors that predict the change from episodic into chronic migraine is of extreme interest and should be seen as a priority in headache research. Potentially remediable risk factors include frequency of migraine attacks, obesity, excessive use of medications containing opioids and barbiturates, caffeine overuse, stressful life events, depression, sleep disorders and cutaneous allodynia. While we wait for evidence regarding the benefits of risk factor modifications in the prevention of chronic migraine, several interventions are justifiable based on their other established benefits. For example, decreasing headache frequency with behavioral and pharmacological interventions will decrease current disability even if it does not modify clinical course. Monitoring the body mass index and encouraging maintenance of normal body weight is good practice in patients with and without migraine. Avoiding overuse of caffeine is desirable apart from its potential benefit in preventing progression. Sleep problems should be investigated and treated. Psychiatric comorbidities should be identified and addressed. Medications containing opioids and barbiturates should be reserved for a few selected cases of migraine, and their use should be monitored. For these interventions, the possibility of preventing progression may motivate clinicians to offer good care and patients to engage in the treatment plan.

Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders.

PubMed

Loechelt, Brett J; Green, Michael; Gottlieb, Peter A; Blumberg, Emily; Weinberg, Adriana; Quinlan, Scott; Baden, Lindsey R

2015-09-01

Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases.

Long-term follow-up after surgery in localized laryngeal amyloidosis.

PubMed

Hazenberg, Aldert J C; Hazenberg, Bouke P C; Dikkers, Frederik G

2016-09-01

To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence rate, revision surgery, progression to systemic amyloidosis, and changes in voice were monitored yearly. Eighteen patients were included. Seven women and eleven men had a median age 50 years (range 21-77 years) and median follow-up 6.4 years (2.4-17 years). Amyloid was located in subglottis (5), glottis (8), false vocal folds (8) and other supraglottic areas (5), in more than one laryngeal region (13) and bilaterally (12). Cold steel excision was used at the glottis; CO2 laser excision, sometimes assisted by microdebrider, at other laryngeal areas. Eleven patients needed revision surgery, ten within the first 4 years after surgical treatment. One patient needed his first revision surgery after 11 years. Five patients needed a second revision within 6 years after initial diagnosis. Two patients needed a third revision. Indications for first revision surgery were progression (8) with dysphonia (7), dyspnea (2), dysphagia (1), exclusion of malignancy (1), and aphonia (1). No patient developed systemic amyloidosis during follow-up. Although local progression of amyloid necessitates revision surgery once or twice in the first 4-6 years, progression slows down thereafter. Late progression, however, remains possible.

Inhibition of mTOR with sirolimus does not attenuate progression of liver and kidney disease in PCK rats.

PubMed

Renken, Catharina; Fischer, Dagmar-Christiane; Kundt, Günther; Gretz, Norbert; Haffner, Dieter

2011-01-01

Activation of the mTOR pathway has been implicated in the mediation of the progression of polycystic kidney disease (PKD). Whereas targeted inhibition of mTOR has been proven to be effective in various animal models of autosomal dominant PKD, its efficacy in autosomal recessive PKD (ARPKD) remains to be elucidated. We examined the effects of sirolimus in PCK rats, an orthologous animal model of human ARPKD. Weaned PCK rats (n = 85) and SD-control rats (n = 72) received drinking water without and with sirolimus (corresponding to a daily intake of 2 mg/kg body weight) for 4, 8 and 12 weeks, respectively. The renal and hepatic functions were monitored throughout the treatment periods. Kidneys and livers were harvested and investigated with respect to progression of fibrosis, and number and size of cysts using the QWin image analysis programme. Expression of Akt, mTOR and its downstream target pS6K were assessed by immunohistochemistry. Five out of 43 sirolimus-treated PCK rats, but none of the controls, died during the study. Sirolimus treatment resulted in slightly reduced weight gain. In PCK rats, grossly enlarged kidney and livers as well as hepatic fibrosis together with enlarged bile ducts were readily detectable. Whereas activation of Akt/mTOR signalling was hardly detectable in the kidneys of SD rats, strong signals were seen in the kidneys of PCK rats. Despite a significantly reduced relative kidney weight after 12 weeks of treatment (P < 0.05), neither fibrosis and cyst area nor renal function improved during treatment. Sirolimus-treated PCK rats showed only a minor inhibition of renal mTOR-specific phosphorylation of S6K. Male PCK rats on sirolimus presented with increased concentrations of bile acids and bilirubin compared with controls (each P < 0.05 at 12 weeks). Similar, albeit non-significant, effects were noted in female PCK rats. Sirolimus failed to attenuate progression of kidney and liver disease in PCK rats. The lack of a protective effect might be due to intrinsic or acquired rapamycin resistance in this animal model of ARPKD.

Recent progress in translational cystic fibrosis research using precision medicine strategies.

PubMed

Cholon, Deborah M; Gentzsch, Martina

2018-03-01

Significant progress has been achieved in developing precision therapies for cystic fibrosis; however, highly effective treatments that target the ion channel, CFTR, are not yet available for many patients. As numerous CFTR therapeutics are currently in the clinical pipeline, reliable screening tools capable of predicting drug efficacy to support individualized treatment plans and translational research are essential. The utilization of bronchial, nasal, and rectal tissues from individual cystic fibrosis patients for drug testing using in vitro assays such as electrophysiological measurements of CFTR activity and evaluation of fluid movement in spheroid cultures, has advanced the prediction of patient-specific responses. However, for precise prediction of drug effects, in vitro models of CFTR rescue should incorporate the inflamed cystic fibrosis airway environment and mimic the complex tissue structures of airway epithelia. Furthermore, novel assays that monitor other aspects of successful CFTR rescue such as restoration of mucus characteristics, which is important for predicting mucociliary clearance, will allow for better prognoses of successful therapies in vivo. Additional cystic fibrosis treatment strategies are being intensively explored, such as development of drugs that target other ion channels, and novel technologies including pluripotent stem cells, gene therapy, and gene editing. The multiple therapeutic approaches available to treat the basic defect in cystic fibrosis combined with relevant precision medicine models provide a framework for identifying optimal and sustained treatments that will benefit all cystic fibrosis patients. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

Baere, Thierry de, E-mail: thierry.debaere@gustaveroussy.fr; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp; Lencioni, Riccardo, E-mail: riccardo.lencioni@med.unipi.it

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has themore » unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014.« less

Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance

PubMed Central

Heydt, Carina; Michels, Sebastian; Thress, Kenneth S.; Bergner, Sven; Wolf, Jürgen; Buettner, Reinhard

2018-01-01

Background The identification and characterization of molecular biomarkers has helped to revolutionize non-small-cell lung cancer (NSCLC) management, as it transitions from target-focused to patient-based treatment, centered on the evolving genomic profile of the individual. Determination of epidermal growth factor receptor (EGFR) mutation status represents a critical step in the diagnostic process. The recent emergence of acquired resistance to “third-generation” EGFR tyrosine kinase inhibitors (TKIs) via multiple mechanisms serves to illustrate the important influence of tumor heterogeneity on prognostic outcomes in patients with NSCLC. Design This literature review examines the emergence of TKI resistance and the course of disease progression and, consequently, the clinical decision-making process in NSCLC. Results Molecular markers of acquired resistance, of which T790M and HER2 or MET amplifications are the most common, help to guide ongoing treatment past the point of progression. Although tissue biopsy techniques remain the gold standard, the emergence of liquid biopsies and advances in analytical techniques may eventually allow “real-time” monitoring of tumor evolution and, in this way, help to optimize targeted treatment approaches. Conclusions The influence of inter- and intra-tumor heterogeneity on resistance mechanisms should be considered when treating patients using resistance-specific therapies. New tools are necessary to analyze changes in heterogeneity and clonal composition during drug treatment. The refinement and standardization of diagnostic procedures and increased accessibility to technology will ultimately help in personalizing the management of NSCLC. PMID:29632655

Non-contact ulcer area calculation system for neuropathic foot ulcer.

PubMed

Shah, Parth; Mahajan, Siddaram; Nageswaran, Sharmila; Paul, Sathish Kumar; Ebenzer, Mannam

2017-08-11

Around 125,785 new cases in year 2013-14 of leprosy were detected in India as per WHO report on leprosy in September 2015 which accounts to approximately 62% of the total new cases. Anaesthetic foot caused by leprosy leads to uneven loading of foot leading to ulcer in approximately 20% of the cases. Much efforts have gone in identifying newer techniques to efficiently monitor the progress of ulcer healing. Current techniques followed in measuring the size of ulcers, have not been found to be so accurate but are still is followed by clinicians across the globe. Quantification of prognosis of the condition would be required to understand the efficacy of current treatment methods and plan for further treatment. This study aims at developing a non contact technique to precisely measure the size of ulcer in patients affected by leprosy. Using MATLAB software, GUI was designed to process the acquired ulcer image by segmenting and calculating the pixel area of the image. The image was further converted to a standard measurement using a reference object. The developed technique was tested on 16 ulcer images acquired from 10 leprosy patients with plantar ulcers. Statistical analysis was done using MedCalc analysis software to find the reliability of the system. The analysis showed a very high correlation coefficient (r=0.9882) between the ulcer area measurements done using traditional technique and the newly developed technique, The reliability of the newly developed technique was significant with a significance level of 99.9%. The designed non-contact ulcer area calculating system using MATLAB is found to be a reliable system in calculating the size of ulcers. The technique would help clinicians have a reliable tool to monitor the progress of ulcer healing and help modify the treatment protocol if needed. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

TPS In-Flight Health Monitoring Project Progress Report

NASA Technical Reports Server (NTRS)

Kostyk, Chris; Richards, Lance; Hudston, Larry; Prosser, William

2007-01-01

Progress in the development of new thermal protection systems (TPS) is reported. New approaches use embedded lightweight, sensitive, fiber optic strain and temperature sensors within the TPS. Goals of the program are to develop and demonstrate a prototype TPS health monitoring system, develop a thermal-based damage detection algorithm, characterize limits of sensor/system performance, and develop ea methodology transferable to new designs of TPS health monitoring systems. Tasks completed during the project helped establish confidence in understanding of both test setup and the model and validated system/sensor performance in a simple TPS structure. Other progress included complete initial system testing, commencement of the algorithm development effort, generation of a damaged thermal response characteristics database, initial development of a test plan for integration testing of proven FBG sensors in simple TPS structure, and development of partnerships to apply the technology.

Statistical shape modeling based renal volume measurement using tracked ultrasound

NASA Astrophysics Data System (ADS)

Pai Raikar, Vipul; Kwartowitz, David M.

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of kidney transplant worldwide accounting for 7-10% of all cases. Although ADPKD usually progresses over many decades, accurate risk prediction is an important task.1 Identifying patients with progressive disease is vital to providing new treatments being developed and enable them to enter clinical trials for new therapy. Among other factors, total kidney volume (TKV) is a major biomarker predicting the progression of ADPKD. Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP)2 have shown that TKV is an early, and accurate measure of cystic burden and likely growth rate. It is strongly associated with loss of renal function.3 While ultrasound (US) has proven as an excellent tool for diagnosing the disease; monitoring short-term changes using ultrasound has been shown to not be accurate. This is attributed to high operator variability and reproducibility as compared to tomographic modalities such as CT and MR (Gold standard). Ultrasound has emerged as one of the standout modality for intra-procedural imaging and with methods for spatial localization has afforded us the ability to track 2D ultrasound in physical space which it is being used. In addition to this, the vast amount of recorded tomographic data can be used to generate statistical shape models that allow us to extract clinical value from archived image sets. In this work, we aim at improving the prognostic value of US in managing ADPKD by assessing the accuracy of using statistical shape model augmented US data, to predict TKV, with the end goal of monitoring short-term changes.

Massive plexiform neurofibromas in childhood: natural history and management issues.

PubMed

Serletis, Demitre; Parkin, Patricia; Bouffet, Eric; Shroff, Manohar; Drake, James M; Rutka, James T

2007-05-01

The authors review their experience with massive plexiform neurofibromas (PNs) in patients with pediatric neurofibromatosis Type 1 (NF1) to better characterize the natural history and management of these complex lesions. The authors performed a retrospective review of data obtained in seven patients with NF1 in whom massive PNs were diagnosed at The Hospital for Sick Children in Toronto, Ontario, Canada. These patients attended routine follow-up examinations conducted by a number of specialists, and serial neuroimaging studies were obtained to monitor disease progression. The most common presenting feature of PN was that of a painful, expanding lesion. Furthermore, two patients harbored multiple, distinct PNs affecting different body sites. With respect to management, two patients were simply observed, undergoing serial neuroimaging studies; two patients underwent biopsy sampling of their plexiform lesions; two patients underwent attempted medical treatment (farnesyl transferase inhibitor, R11577, and cyclophosphamide chemotherapy); and three patients required surgical debulking of their PNs because the massive growth of these tumors caused functional compromise. Ultimately, one patient died of respiratory complications due to progressive growth of the massive PN lesion. In this review of their experience, the authors found certain features that underscore the presentation and natural history of PNs. The management of these complex lesions, however, remains unclear. Slow-growing PNs may be observed conservatively, but the authors' experience suggests that resection should be considered in selected cases involving significant deterioration or functional compromise. Nevertheless, patients with massive PNs will benefit from close surveillance by a team of specialists to monitor for ongoing disease progression.

Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste

PubMed Central

Al Khasawnah, Qusai; Hassan, Fathi; Malhan, Deeksha; Engelhardt, Markus; Daghma, Diaa Eldin S.; Obidat, Dima; Lips, Katrin S.; Heiss, Christian

2018-01-01

Background The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. Materials and Methods Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. Results No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. Conclusion CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase. PMID:29619378

Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

PubMed Central

Cox, Thomas R.; Erler, Janine T.

2011-01-01

Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM. PMID:21324931

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer

PubMed Central

Wei, Fang; Wong, David T.; Su, Wu-Chou

2015-01-01

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer. PMID:26448936

14 CFR 417.23 - Compliance monitoring.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Compliance monitoring. 417.23 Section 417... Compliance monitoring. (a) A launch operator must allow access by, and cooperate with, Federal officers or... launch operator must provide the FAA with a console for monitoring the progress of the countdown and...

Serum levels of endothelial and neural cell adhesion molecules in prostate cancer.

PubMed

Lynch, D F; Hassen, W; Clements, M A; Schellhammer, P F; Wright, G L

1997-08-01

Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell lung carcinoma (SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease. Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring CaP patients following definitive radiotherapy, radical prostatectomy, or hormonal therapy. The results of this study indicate that serum ICAM-1, VCAM-1, NCAM, and E-selectin are not clinically useful biomarkers for differentiating CaP from BPH, for predicting progression, for identifying metastatic potential, or for monitoring treatment.

Ten-Year Summary and Evaluation of Operations and Performance of the Utica Aquifer and North Lake Basin Wetlands Restoration Project, 2004-2014

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

LaFreniere, Lorraine M.

This document reviews the performance of the groundwater (and wetlands) restoration program implemented by the Commodity Credit Corporation of the U.S. Department of Agriculture (CCC/USDA) at the former CCC/USDA grain storage facility in Utica, Nebraska, during the first ten years of this initiative (2004-2014). The results of the program for the first five-year period of operation were previously discussed in detail (Argonne 2011). The present report focuses on treatment system operational data and regulatory compliance monitoring results for the site during the second five-year period of operation (2010-2014), together with the results of (1) ongoing monitoring and (2) targeted groundwatermore » sampling for volatile organic compounds (VOCs) analyses conducted at Utica in 2015 (following completion of the tenth year of systems operation), to assess the 10-year progress of the Utica remediation effort.« less

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds

PubMed Central

Farooqui, Muhammad Fahad; Shamim, Atif

2016-01-01

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications. PMID:27353200

Innovative approaches to glaucoma management of Boston keratoprosthesis type 1.

PubMed

Vajaranant, Thasarat S; Liu, Jessica; Wilensky, Jacob; Cortina, M Soledad; Aref, Ahmad A

2016-09-01

Glaucoma remains a prevalent disorder and visual limiting factor after Boston keratoprosthesis type 1 implantation. Patients with glaucoma have worse initial and late visual acuity outcomes after otherwise successful keratoprosthesis implantation. Management of glaucoma in the setting of a keratoprosthesis is challenging because of relatively rapid progression and an inability to accurately measure intraocular pressure (IOP). In addition, there are no standard guidelines for glaucoma surveillance and monitoring after keratoprosthesis surgery. This report provides a review of the current literature and offers innovative strategies that will overcome the challenges in managing glaucoma in the setting of a Boston keratoprosthesis type 1 implant. The topics that will be discussed in this section include alternative methods for IOP measurement, rationales and surgical techniques for a pars plana tube placement for glaucoma drainage device, effective medical and laser treatment, the risk for IOP elevations after YAG laser, and practical guides to glaucoma surveillance and monitoring.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds

NASA Astrophysics Data System (ADS)

Farooqui, Muhammad Fahad; Shamim, Atif

2016-06-01

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

Imaging Patterns of Muscle Atrophy.

PubMed

Weber, Marc-André; Wolf, Marcel; Wattjes, Mike P

2018-07-01

The role of muscle imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI) is increasingly being used for diagnostic purposes, especially with its capability of whole-body musculature assessment. The assessment and quantification of muscle involvement in muscle diseases can be of diagnostic value by identifying a certain involvement pattern and thus narrowing the differential diagnosis and supporting the clinical diagnosis. In addition, more recently the role of imaging has gone beyond diagnostic purposes and includes disease as well as treatment monitoring. Conventional and quantitative muscle MRI techniques allow for the detection of subclinical disease progression (e.g., in muscular dystrophies) and is a powerful surrogate outcome measure in clinical trials. We present and discuss recent data on the role of conventional and quantitative MRI in the diagnosis and monitoring of inherited dystrophic muscle diseases as well as muscle denervation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The role of the pharmacist in optimizing the use of erythropoietin stimulating agents.

PubMed

Gebara, Shereen Nabhani; Moubayed, Hiba

2010-03-01

With the emerging new warnings surrounding the use of erythropoiesis-stimulating agents (ESAs), the pharmacist's role as health educator and risk communicator expands further to include patient scrutiny to check for eligibility and patient monitoring to check for response or toxicity. This review explores the benefits and risks linked to ESAs use, and the proposed role. ESAs have been increasingly used for the treatment of chemotherapy-induced anemia because of its documented effect on decreasing transfusion dependency. However, their use has been associated with thromboembolic complications, tumor progression, and decreased overall survival. This review covers current recommendations and guidelines that surround ESAs use in the supportive care of cancer patients. To minimize or prevent the complications associated with ESAs use, cancer patients should be adequately monitored and counseled. This highlights the importance of the pharmacist's involvement to optimize patient care.

The role of environmental biotechnology in exploring, exploiting, monitoring, preserving, protecting and decontaminating the marine environment.

PubMed

Kalogerakis, Nicolas; Arff, Johanne; Banat, Ibrahim M; Broch, Ole Jacob; Daffonchio, Daniele; Edvardsen, Torgeir; Eguiraun, Harkaitz; Giuliano, Laura; Handå, Aleksander; López-de-Ipiña, Karmele; Marigomez, Ionan; Martinez, Iciar; Øie, Gunvor; Rojo, Fernando; Skjermo, Jorunn; Zanaroli, Giulio; Fava, Fabio

2015-01-25

In light of the Marine Strategy Framework Directive (MSFD) and the EU Thematic Strategy on the Sustainable Use of Natural Resources, environmental biotechnology could make significant contributions in the exploitation of marine resources and addressing key marine environmental problems. In this paper 14 propositions are presented focusing on (i) the contamination of the marine environment, and more particularly how to optimize the use of biotechnology-related tools and strategies for predicting and monitoring contamination and developing mitigation measures; (ii) the exploitation of the marine biological and genetic resources to progress with the sustainable, eco-compatible use of the maritime space (issues are very diversified and include, for example, waste treatment and recycling, anti-biofouling agents; bio-plastics); (iii) environmental/marine biotechnology as a driver for a sustainable economic growth. Copyright © 2014 Elsevier B.V. All rights reserved.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds.

PubMed

Farooqui, Muhammad Fahad; Shamim, Atif

2016-06-29

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

Comparison of Standard Automated Perimetry, Short-Wavelength Automated Perimetry, and Frequency-Doubling Technology Perimetry to Monitor Glaucoma Progression

PubMed Central

Hu, Rongrong; Wang, Chenkun; Gu, Yangshun; Racette, Lyne

2016-01-01

Abstract Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression. Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models. No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP. SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes. PMID:26886602

Monitoring interferon β treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis.

PubMed

Yetkin, Mehmet Fatih; Mirza, Meral; Dönmez, Halil

2016-09-01

The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment.At the end of 1 year follow up, 26 of 36 patients completed the study. In patients' white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients' white matter lesions and normal appearing white matter did not change statistically.This study showed that in MS patients' white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls' normal white matter; and in the patients treated with interferon β NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon β therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS.

Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study.

PubMed

Roschewski, Mark; Dunleavy, Kieron; Pittaluga, Stefania; Moorhead, Martin; Pepin, Francois; Kong, Katherine; Shovlin, Margaret; Jaffe, Elaine S; Staudt, Louis M; Lai, Catherine; Steinberg, Seth M; Chen, Clara C; Zheng, Jianbiao; Willis, Thomas D; Faham, Malek; Wilson, Wyndham H

2015-05-01

Diffuse large-B-cell lymphoma is curable, but when treatment fails, outcome is poor. Although imaging can help to identify patients at risk of treatment failure, they are often imprecise, and radiation exposure is a potential health risk. We aimed to assess whether circulating tumour DNA encoding the clonal immunoglobulin gene sequence could be detected in the serum of patients with diffuse large-B-cell lymphoma and used to predict clinical disease recurrence after frontline treatment. We used next-generation DNA sequencing to retrospectively analyse cell-free circulating tumour DNA in patients assigned to one of three treatment protocols between May 8, 1993, and June 6, 2013. Eligible patients had diffuse large-B-cell lymphoma, no evidence of indolent lymphoma, and were previously untreated. We obtained serial serum samples and concurrent CT scans at specified times during most treatment cycles and up to 5 years of follow-up. VDJ gene segments of the rearranged immunoglobulin receptor genes were amplified and sequenced from pretreatment specimens and serum circulating tumour DNA encoding the VDJ rearrangements was quantitated. Tumour clonotypes were identified in pretreatment specimens from 126 patients who were followed up for a median of 11 years (IQR 6·8-14·2). Interim monitoring of circulating tumour DNA at the end of two treatment cycles in 108 patients showed a 5-year time to progression of 41·7% (95% CI 22·2-60·1) in patients with detectable circulating tumour DNA and 80·2% (69·6-87·3) in those without detectable circulating tumour DNA (p<0·0001). Detectable interim circulating tumour DNA had a positive predictive value of 62·5% (95% CI 40·6-81·2) and a negative predictive value of 79·8% (69·6-87·8). Surveillance monitoring of circulating tumour DNA was done in 107 patients who achieved complete remission. A Cox proportional hazards model showed that the hazard ratio for clinical disease progression was 228 (95% CI 51-1022) for patients who developed detectable circulating tumour DNA during surveillance compared with patients with undetectable circulating tumour DNA (p<0·0001). Surveillance circulating tumour DNA had a positive predictive value of 88·2% (95% CI 63·6-98·5) and a negative predictive value of 97·8% (92·2-99·7) and identified risk of recurrence at a median of 3·5 months (range 0-200) before evidence of clinical disease. Surveillance circulating tumour DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumour DNA is a promising biomarker to identify patients at high risk of treatment failure. National Cancer Institute and Adaptive Biotechnologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice.

PubMed

Jansen, Natalie; Walach, Harald

2016-01-01

Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials.

The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice

PubMed Central

JANSEN, NATALIE; WALACH, HARALD

2016-01-01

Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials. PMID:26870251

Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

PubMed

Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

2017-09-15

Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC 50 ) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer.

PubMed

Ma, Xiaopeng; Phi Van, Valerie; Kimm, Melanie A; Prakash, Jaya; Kessler, Horst; Kosanke, Katja; Feuchtinger, Annette; Aichler, Michaela; Gupta, Aayush; Rummeny, Ernst J; Eisenblätter, Michel; Siveke, Jens; Walch, Axel K; Braren, Rickmer; Ntziachristos, Vasilis; Wildgruber, Moritz

2017-01-01

Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib) for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Crevicular Fluid Biomarkers and Periodontal Disease Progression

PubMed Central

Oh, Min; Braun, Thomas M.; Ramseier, Christoph A.; Sugai, Jim V.; Giannobile, William V.

2014-01-01

Aim Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). Materials and Methods 100 individuals participated in a 12-month longitudinal investigation and categorized into 4 groups according to their periodontal status. GCF, clinical parameters, and saliva were collected bi-monthly. Sub-gingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6-months, patients received periodontal therapy and continued participation from 6-12 months. GCF samples were analyzed by ELISA for MMP-8, MMP-9, OPG, CRP and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p=0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Results Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61,86). Conclusions Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). PMID:24303954

Progress and challenges in implementing HIV care and treatment policies in Latin America following the treatment 2.0 initiative.

PubMed

Perez, Freddy; Gomez, Bertha; Ravasi, Giovanni; Ghidinelli, Massimo

2015-12-19

The Pan American Health Organization provides technical cooperation to countries in Latin America and the Caribbean for the scale-up of HIV care and treatment based on the Treatment 2.0 initiative. Fourteen Joint Review Missions (JRMs) were conducted between March 2012 and October 2014. Evaluating the degree of implementation of the recommendations of the JRMs and their impact on health policies, would help countries identify their gaps and areas for priority interventions. A descriptive analysis of the JRM recommendations was conducted for eight countries. An in-depth cross-sectional retrospective analysis of the degree of implementation of these recommendations in Ecuador, Venezuela, Bolivia, and El Salvador was performed through a standardized self-administered questionnaire applied to key informants. A comparative quantitative analysis on the optimization of antiretroviral regimens 'before/after' JRMs was conducted in three of the latter four countries, using data reported in 2013 and 2014. The priority areas with most recommendations were the optimization of antiretroviral treatment (ART) regimens (n = 57), the rational and efficient use of resources (n = 27) and the provision of point-of-care diagnostics and monitoring tools (n = 26), followed by community mobilization (n = 23), strategic information (n = 17) and the adaptation of delivery services (n = 15). The in-depth analysis in four countries showed that the two priority areas where most progress was observed were the rational and efficient use of resources (62%) and the optimization of ART regimens (60%). Adaptation of delivery services, community mobilization and strategic information were rated at 52% and the provision of point-of-care diagnostics and monitoring tools 38%. The quantitative analysis on optimization evidenced a 36% reduction in the number of first-line and second-line ART regimens, a 5.4% increase in the proportion of patients on WHO-recommended first-line regimens, a 19.4% increase in the use of the WHO preferred first-line regimen, 51% increase in the use of WHO-recommended second-line regimens, and a significant reduction in the use of obsolete drugs in first- and second-line regimens (respectively 1 and 9% of regimens in 2013). A relatively good level of progress was perceived in the recommendations related to optimization of ART regimens. Challenges remain on the improvement of recommendations related to health system strengthening and the promotion and support aimed at community-based organizations as part of the response to HIV/AIDS in Latin America. The JRMs are a useful mechanism for providing coherent technical support to guide countries in the pursuit of a comprehensive response to HIV/AIDS in the Latin American region.

Tumor-derived exosomes in ovarian cancer – liquid biopsies for early detection and real-time monitoring of cancer progression

PubMed Central

Sharma, Shayna; Zuñiga, Felipe; Rice, Gregory E.; Perrin, Lewis C.; Hooper, John D.; Salomon, Carlos

2017-01-01

Ovarian cancer usually has a poor prognosis because it predominantly presents as high stage disease. New approaches are required to develop more effective early detection strategies and real-time treatment response monitoring. Nano-sized extracellular vesicles (EVs, including exosomes) may provide an approach to enrich tumor biomarker detection and address this clinical need. Exosomes are membranous extracellular vesicles of approximately 100 nm in diameter that have potential to be used as biomarkers and therapeutic delivery tools for ovarian cancer. Exosomal content (proteins and miRNA) is often parent cell specific thus providing an insight or “fingerprint” of the intracellular environment. Furthermore, exosomes can aid cell-cell communication and have the ability to modify target cells by transferring their content. Additionally, via the capacity to evade the immune system and remain stable over long periods in circulation, exosomes have potential as natural drug agents. This review examines the potential role of exosomes in diagnosis, drug delivery and real-time monitoring in ovarian cancer. PMID:29262670

Options for the Development of Noninvasive Glucose Monitoring: Is Nanotechnology an Option to Break the Boundaries?

PubMed

Thomas, Andreas; Heinemann, Lutz; Ramírez, Araceli; Zehe, Alfred

2016-05-01

Nowadays nanotechnology has many applications in products used in various areas of daily life; however, this technology has also an option in modern medicine and pharmacy. Therefore, this technology is also an attractive option for the field of diagnosis and treatment of diabetes. Many people with diabetes measure their blood glucose levels regularly to determine the insulin dose. Ideally glucose values would be measured noninvasively (NI). However, none of all the NI approaches studied in the past decades enabled reliable NI measurements under all daily life conditions. Particularly an unfavorable signal-to-noise ratio turned out to be problematic. Based on the known physical possibilities for NI glucose monitoring the focus of this review is on nanotechnology approaches. Functional prototypes exist for some of these that showed promising results under defined laboratory conditions, indicating a good sensitivity and selectivity for glucose. On the second hand is to optimize the technological process of manufacturing. In view of the rapid progress in micro- and nanoelectronics hopefully NI glucose monitoring systems can be developed in the near future. © 2015 Diabetes Technology Society.

Quantification of proteins in urine samples using targeted mass spectrometry methods.

PubMed

Khristenko, Nina; Domon, Bruno

2015-01-01

Numerous clinical proteomics studies are focused on the development of biomarkers to improve either diagnostics for early disease detection or the monitoring of the response to the treatment. Although, a wealth of biomarker candidates are available, their evaluation and validation in a true clinical setup remains challenging. In biomarkers evaluation studies, a panel of proteins of interest are systematically analyzed in a large cohort of samples. However, in spite of the latest progresses in mass spectrometry, the consistent detection of pertinent proteins in high complex biological samples is still a challenging task. Thus, targeted LC-MS/MS methods are better suited for the systematic analysis of biomarkers rather than shotgun approaches. This chapter describes the workflow used to perform targeted quantitative analyses of proteins in urinary samples. The peptides, as surrogates of the protein of interest, are commonly measured using a triple quadrupole mass spectrometers operated in selected reaction monitoring (SRM) mode. More recently, the advances in targeted LC-MS/MS analysis based on parallel reaction monitoring (PRM) performed on a quadrupole-orbitrap instrument have allowed to increase the specificity and selectivity of the measurements.

Options for the Development of Noninvasive Glucose Monitoring

PubMed Central

Thomas, Andreas; Heinemann, Lutz; Ramírez, Araceli; Zehe, Alfred

2015-01-01

Nowadays nanotechnology has many applications in products used in various areas of daily life; however, this technology has also an option in modern medicine and pharmacy. Therefore, this technology is also an attractive option for the field of diagnosis and treatment of diabetes. Many people with diabetes measure their blood glucose levels regularly to determine the insulin dose. Ideally glucose values would be measured noninvasively (NI). However, none of all the NI approaches studied in the past decades enabled reliable NI measurements under all daily life conditions. Particularly an unfavorable signal-to-noise ratio turned out to be problematic. Based on the known physical possibilities for NI glucose monitoring the focus of this review is on nanotechnology approaches. Functional prototypes exist for some of these that showed promising results under defined laboratory conditions, indicating a good sensitivity and selectivity for glucose. On the second hand is to optimize the technological process of manufacturing. In view of the rapid progress in micro- and nanoelectronics hopefully NI glucose monitoring systems can be developed in the near future. PMID:26581879

A wearable device for monitoring and prevention of repetitive ankle sprain.

PubMed

Attia, Mohammed; Taher, Mona F

2015-01-01

This study presents the design and implementation of a wearable wireless device, connected to a smart phone, which monitors and prevents repetitive ankle sprain due to chronic ankle instability (CAI). The device prevents this common foot injury by electrical stimulation of the peroneal muscles using surface electrodes which causes dorsiflexion of the foot. This is done after measuring ankle kinematics using inertial motion sensors and predicting ankle sprain. The prototype implemented here has a fast response time of 7 msec which enables prevention of ankle sprain before ligament damage occurs. Wireless communication between the components of the device, in addition to their small size, low cost and low power consumption, makes it unobtrusive, easy to wear and not hinder normal activities. The device connects via Bluetooth to an android smart phone application for continuous data logging and reporting to keep track of the incidences of possible ankle sprain and correction. This is a significant feature of this device since it enables monitoring of patients with CAI and quantifying progression of the condition or improvement in the case of treatment.

Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for mechlorethamine release and spatiotemporal monitoring.

PubMed

Cao, Yanting; Pan, Rong; Xuan, Weimin; Wei, Yongyi; Liu, Kejian; Zhou, Jiahong; Wang, Wei

2015-06-28

We describe a new theranostic strategy for selective delivery and spatiotemporal monitoring of mechlorethamine, a DNA alkylating agent. A photo-responsive prodrug is designed and composed of a photolabile o-nitrophenylethyl group, a DNA alkylating mechlorethamine drug and a coumarin fluorophore. Masking of the "N" in mechlorethamine in a positively charged state in the prodrug renders it inactive, non-toxic, selective and non-fluorescent. Indeed, the stable prodrug shows negligible cytotoxicity towards normal cells with and without UV activation and is completely non-fluorescent. However, upon photo-irradiation, the active mechlorethamine is released and induces efficient DNA cross-links, accompanied by a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking activity from the release can be transformed into anticancer activity observed in in vitro studies of tumor cells. Importantly, the drug release progress and the movement can be conveniently monitored by fluorescence spectroscopy. The mechanistic study proves that the DNA cross-linking activity is mainly due to the release of DNA alkylating mechlorethamine. Altogether, the studies show the power of the theranostic strategy for efficient therapy in cancer treatment.

Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties.

PubMed

Panahifar, A; Jaremko, J L; Tessier, A G; Lambert, R G; Maksymowych, W P; Fallone, B G; Doschak, M R

2014-10-01

We sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA. Post-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment. Disease progression was monitored utilizing micro-magnetic resonance imaging (MRI), micro-computed tomography (CT) and histology. Pertinent features such as osteophytes, subchondral sclerosis, joint effusion, bone marrow lesion (BML), cysts, loose bodies and cartilage abnormalities were included in designing a sensitive multi-modality based scoring system, termed the rat arthritis knee scoring system (RAKSS). Overall, an inter-observer correlation coefficient (ICC) of greater than 0.750 was achieved for each scored feature. None of the treatments prevented cartilage loss, synovitis, joint effusion, or sclerosis. However, celecoxib significantly reduced osteophyte development compared to placebo. Although signs of inflammation such as synovitis and joint effusion were readily identified at 4 weeks post-operation, we did not detect any BML. We report the development of a sensitive and reliable multi-modality scoring system, the RAKSS, for evaluation of OA severity in pre-clinical animal models. Using this scoring system, we found that celecoxib prevented enlargement of osteophytes in this animal model of PTOA, and thus it may be useful in preventing OA progression. However, it did not show any chondroprotective effect using the recommended dose. In contrast, high dose glucosamine had no measurable effects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The development of a disease oriented eFolder for multiple sclerosis decision support

NASA Astrophysics Data System (ADS)

Ma, Kevin; Jacobs, Colin; Fernandez, James; Amezcua, Lilyana; Liu, Brent

2010-03-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The chronic nature of MS necessitates multiple MRI studies to track disease progression. Currently, MRI assessment of multiple sclerosis requires manual lesion measurement and yields an estimate of lesion volume and change that is highly variable and user-dependent. In the setting of a longitudinal study, disease trends and changes become difficult to extrapolate from the lesions. In addition, it is difficult to establish a correlation between these imaged lesions and clinical factors such as treatment course. To address these clinical needs, an MS specific e-Folder for decision support in the evaluation and assessment of MS has been developed. An e-Folder is a disease-centric electronic medical record in contrast to a patient-centric electronic health record. Along with an MS lesion computer aided detection (CAD) package for lesion load, location, and volume, clinical parameters such as patient demographics, disease history, clinical course, and treatment history are incorporated to make the e-Folder comprehensive. With the integration of MRI studies together with related clinical data and informatics tools designed for monitoring multiple sclerosis, it provides a platform to improve the detection of treatment response in patients with MS. The design and deployment of MS e-Folder aims to standardize MS lesion data and disease progression to aid in decision making and MS-related research.

Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

PubMed

Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

2012-02-15

Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P < .001). At all ages, lower counts before treatment were associated with impaired recovery (P < .001). Age-adjusted naive CD4 counts increased on a timescale comparable to overall CD4 T-cell reconstitution, whereas age-adjusted memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

Combination of Anti-angiogenesis with Chemotherapy for More Effective Cancer Treatment*

PubMed Central

Ma, Jie; Waxman, David J.

2008-01-01

Angiogenesis is a hallmark of tumor development and metastasis and is now a validated target for cancer treatment. Overall, however, the survival benefits of anti-angiogenic drugs have, thus far, been rather modest, stimulating interest in developing more effective ways to combine anti-angiogenic drugs with established chemotherapies. This review discusses recent progress and emerging challenges in this field; interactions between anti-angiogenic drugs and conventional chemotherapeutic agents are examined, and strategies for the optimization of combination therapies are discussed. Anti-angiogenic drugs such as the anti-VEGF antibody bevacizumab can induce a functional normalization of the tumor vasculature that is transient and can potentiate the activity of co-administered chemoradiotherapies. However, chronic angiogenesis inhibition typically reduces tumor uptake of co-administered chemotherapeutics, indicating a need to explore new approaches, including intermittent treatment schedules and provascular strategies to increase chemotherapeutic drug exposure. In cases where anti-angiogenesis-induced tumor cell starvation augments the intrinsic cytotoxic effects of a conventional chemotherapeutic drug, combination therapy may increase anti-tumor activity despite a decrease in cytotoxic drug exposure. As new angiogenesis inhibitors enter the clinic, reliable surrogate markers are needed to monitor the progress of anti-angiogenic therapies and to identify responsive patients. New targets for anti-angiogenesis continue to be discovered, increasing the opportunities to interdict tumor angiogenesis and circumvent resistance mechanisms that may emerge with chronic use of these drugs. PMID:19074844

Neuroprotection for the new millennium. Matchmaking pharmacology and technology

NASA Technical Reports Server (NTRS)

Andrews, R. J.

2001-01-01

A major theme of the 1990s in the pathophysiology of nervous system injury has been the multifactorial etiology of irreversible injury. Multiple causes imply multiple opportunities for therapeutic intervention--hence the abandonment of the "magic bullet" single pharmacologic agent for neuroprotection in favor of pharmacologic "cocktails". A second theme of the 1990s has been the progress in technology for neuroprotection, minimally- or non-invasive monitoring as well as treatment. Cardiac stenting has eliminated the need, in many cases, for open heart surgery; deep brain stimulation for Parkinson's disease has offered significant improvement in quality of life for many who had exhausted cocktail drug treatment for their disease. Deep brain stimulation of the subthalamic nucleus offers a novel treatment for Parkinson's disease where a technological advance may actually be an intervention with effects that are normally expected from pharmacologic agents. Rather than merely "jamming" the nervous system circuits involved in Parkinson's disease, deep brain stimulation of the subthalamic nucleus appears to improve the neurotransmitter imbalance that lies at the heart of Parkinson's disease. It may also slow the progression of the disease. Given the example of deep brain stimulation of the subthalamic nucleus for Parkinson's disease, in future one may expect other technological or "hardware" interventions to influence the programming or "software" of the nervous system's physiologic response in certain disease states.

Progress in increasing affordability of medicines for non-communicable diseases since the introduction of mandatory health insurance in the Republic of Moldova

PubMed Central

Ferrario, Alessandra; Chitan, Elena; Seicas, Rita; Sautenkova, Nina; Bezverhni, Zinaida; Kluge, Hans; Habicht, Jarno

2016-01-01

Background: To assess progress in improving affordability of medicines since the introduction of mandatory health insurance in the Republic of Moldova. Method: Using data from national health insurance, we estimate affordability of partially reimbursed medicines for the treatment of non-communicable diseases, and analyse which factors contributed to changes in affordability. Results: Affordability of subsidized medicines improved over time. In 2013, it took a median of 0.84 days of income for the lowest income quintile (ranging from 0 to 3.32 days) to purchase 1 month of treatment for cardiovascular conditions in comparison to 1.85 days in 2006. This improvement however was mainly driven by higher incomes rather than deeper coverage through the reimbursement list. Conclusion: If mandatory health insurance is to improve affordability of medicines for the Moldovan population, more funds need to be (re-)allocated to enable higher percentage coverage of essential medicines and efficiencies need to be generated within the health system. These should include a budget reallocation between secondary and primary care, strengthening primary care to manage chronic conditions and raise population awareness, implementation of evidence-based selection and quality use of medicines in both outpatient and inpatient settings, improving monitoring and regulation of prices and the supply chain; and alignment of national treatment guidelines and clinical practice with international best practices and evidence-based medicine. PMID:26830363

Charge-carrier relaxation in sonochemically fabricated dendronized CaSiO3-SiO2-Si nanoheterostructures

NASA Astrophysics Data System (ADS)

Savkina, Rada; Smirnov, Aleksey; Kirilova, Svitlana; Shmid, Volodymyr; Podolian, Artem; Nadtochiy, Andriy; Odarych, Volodymyr; Korotchenkov, Oleg

2018-04-01

We present systematic studies of charge-carrier relaxation processes in sonochemically nanostructured silicon wafers. Impedance spectroscopy and transient photovoltage techniques are employed. It is found that interface potential in Si wafers remarkably increases upon their exposure to sonochemical treatments in Ca-rich environments. In contrast, the density of fast interface electron states remains almost unchanged. It is found that the initial photovoltage decay, taken before ultrasonic treatments, exhibits the involvement of shorter- and longer time recombination and trapping centers. The decay speeds up remarkably due to cavitation treatments, which is accompanied by a substantial quenching of the photovoltage magnitude. It is also found that, before the treatments, the photovoltage magnitude is markedly non-uniform over the wafer surface, implying the existence of distributed sites affecting distribution of photoexcited carriers. The treatments cause an overall broadening of the photovoltage distribution. Furthermore, impedance measurements monitor the progress in surface structuring relevant to several relaxation processes. We believe that sonochemical nanostructuring of silicon wafers with dendronized CaSiO3 may enable new promising avenue towards low-cost solar energy efficiency multilayered solar cell device structures.

Application of adenosine triphosphate affinity probe and scheduled multiple-reaction monitoring analysis for profiling global kinome in human cells in response to arsenite treatment.

PubMed

Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng

2014-11-04

Phosphorylation of cellular components catalyzed by kinases plays important roles in cell signaling and proliferation. Quantitative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the mechanisms underlying the cytotoxic effects of environmental toxicants. Here, we utilized an adenosine triphosphate (ATP) affinity probe coupled with stable isotope labeling by amino acids in cell culture (SILAC) to assess quantitatively the arsenite-induced alteration of global kinome in human cells. We constructed a SILAC-compatible kinome library for scheduled multiple-reaction monitoring (MRM) analysis and adopted on-the-fly recalibration of retention time shift, which provided better throughput of the analytical method and enabled the simultaneous quantification of the expression of ∼300 kinases in two LC-MRM runs. With this improved analytical method, we conducted an in-depth quantitative analysis of the perturbation of kinome of GM00637 human skin fibroblast cells induced by arsenite exposure. Several kinases involved in cell cycle progression, including cyclin-dependent kinases (CDK1 and CDK4) and Aurora kinases A, B, and C, were found to be hyperactivated, and the altered expression of CDK1 was further validated by Western analysis. In addition, treatment with a CDK inhibitor, flavopiridol, partially restored the arsenite-induced growth inhibition of human skin fibroblast cells. Thus, sodium arsenite may confer its cytotoxic effect partly through the aberrant activation of CDKs and the resultant perturbation of cell cycle progression. Together, we developed a high-throughput, SILAC-compatible, and MRM-based kinome profiling method and demonstrated that the method is powerful in deciphering the molecular modes of action of a widespread environmental toxicant. The method should be generally applicable for uncovering the cellular pathways triggered by other extracellular stimuli.

Application of Adenosine Triphosphate Affinity Probe and Scheduled Multiple-Reaction Monitoring Analysis for Profiling Global Kinome in Human Cells in Response to Arsenite Treatment

PubMed Central

2015-01-01

Phosphorylation of cellular components catalyzed by kinases plays important roles in cell signaling and proliferation. Quantitative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the mechanisms underlying the cytotoxic effects of environmental toxicants. Here, we utilized an adenosine triphosphate (ATP) affinity probe coupled with stable isotope labeling by amino acids in cell culture (SILAC) to assess quantitatively the arsenite-induced alteration of global kinome in human cells. We constructed a SILAC-compatible kinome library for scheduled multiple-reaction monitoring (MRM) analysis and adopted on-the-fly recalibration of retention time shift, which provided better throughput of the analytical method and enabled the simultaneous quantification of the expression of ∼300 kinases in two LC-MRM runs. With this improved analytical method, we conducted an in-depth quantitative analysis of the perturbation of kinome of GM00637 human skin fibroblast cells induced by arsenite exposure. Several kinases involved in cell cycle progression, including cyclin-dependent kinases (CDK1 and CDK4) and Aurora kinases A, B, and C, were found to be hyperactivated, and the altered expression of CDK1 was further validated by Western analysis. In addition, treatment with a CDK inhibitor, flavopiridol, partially restored the arsenite-induced growth inhibition of human skin fibroblast cells. Thus, sodium arsenite may confer its cytotoxic effect partly through the aberrant activation of CDKs and the resultant perturbation of cell cycle progression. Together, we developed a high-throughput, SILAC-compatible, and MRM-based kinome profiling method and demonstrated that the method is powerful in deciphering the molecular modes of action of a widespread environmental toxicant. The method should be generally applicable for uncovering the cellular pathways triggered by other extracellular stimuli. PMID:25301106

Changing treatment paradigms for the management of inflammatory bowel disease.

PubMed

Im, Jong Pil; Ye, Byong Duk; Kim, You Sun; Kim, Joo Sung

2018-01-01

Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the management of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of immunosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conventional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parameters such as endoscopic healing due to the discrepancies observed between symptoms, objectively evaluated inf lammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients' preferences.

Randomized trial of the ForeseeHome monitoring device for early detection of neovascular age-related macular degeneration. The HOme Monitoring of the Eye (HOME) study design - HOME Study report number 1.

PubMed

Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard A

2014-03-01

To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients. Published by Elsevier Inc.

Development of an impairment-based individualized treatment workflow using an iPad-based software platform.

PubMed

Kiran, Swathi; Des Roches, Carrie; Balachandran, Isabel; Ascenso, Elsa

2014-02-01

Individuals with language and cognitive deficits following brain damage likely require long-term rehabilitation. Consequently, it is a huge practical problem to provide the continued communication therapy that these individuals require. The present project describes the development of an impairment-based individualized treatment workflow using a software platform called Constant Therapy. This article is organized into two sections. We will first describe the general methods of the treatment workflow for patients involved in this study. There are four steps in this process: (1) the patient's impairment is assessed using standardized tests, (2) the patient is assigned a specific and individualized treatment plan, (3) the patient practices the therapy at home and at the clinic, and (4) the clinician and the patient can analyze the results of the patient's performance remotely and monitor and alter the treatment plan accordingly. The second section provides four case studies that provide a representative sample of participants progressing through their individualized treatment plan. The preliminary results of the patient treatment provide encouraging evidence for the feasibility of a rehabilitation program for individuals with brain damage based on the iPad (Apple Inc., Cupertino, CA). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel remote electronic medication supply model for opioid-dependent outpatients with polypharmacy--first long-term case study.

PubMed

Allemann, Samuel S; Dürsteler, Kenneth M; Strasser, Johannes; Vogel, Marc; Stoeckle, Marcel; Hersberger, Kurt E; Arnet, Isabelle

2017-08-16

Patients with substance use disorders grow older thanks to effective treatments. Together with a high prevalence of comorbidities, psychological problems, and low social support, these patients are at high risk for medication non-adherence. Established treatment facilities face challenges to accommodate these complex patients within their setting. Electronic medication management aids (e-MMAs) might be appropriate to simultaneously monitor and improve adherence for these patients. We report the first long-term experiences with a novel remote electronic medication supply model for two opioid-dependent patients with HIV. John (beginning dementia, 52 years, 6 tablets daily at 12 am) and Mary (frequent drug holidays, 48 years, 5-6 tablets daily at 8 pm) suffered from disease progression due to non-adherence. We electronically monitored adherence and clinical outcomes during 659 (John) and 953 (Mary) days between July 2013 and April 2016. Both patients retrieved over 90% of the pouches within 75 min of the scheduled time. Technical problems occurred in 4% (John) and 7.2% (Mary) of retrievals, but on-site support was seldom required. Viral loads fell below detection limits during the entire observation period. Continuous medication supply and persistence with treatment of over 1.7 years, timing adherence of more than 90%, and suppressed HIV viral load are first results supporting the feasibility of the novel supply model for patients on opioid-assisted treatment and polypharmacy.

Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.

PubMed

Rollman, O; Vahlquist, A

1986-04-01

The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.

GLYCEMIC CONTROL AND BURNT-OUT Diabetes IN ESRD

PubMed Central

Kovesdy, Csaba P; Park, J.C.; Kalantar-Zadeh, Kamyar

2017-01-01

Treatment of early diabetes mellitus, the most common cause of chronic kidney disease (CKD), may prevent or slow the progression of diabetic nephropathy and lower mortality and the incidence of cardiovascular disease in the general diabetic population and in patients with early stages of CKD. It is unclear whether glycemic control in patients with advanced CKD, including those with end-stage renal disease (ESRD) who undergo maintenance dialysis treatment is beneficial. Aside from the uncertain benefits of treatment in ESRD, hypoglycemic interventions in this population are also complicated by the complex changes in glucose homeostasis related to decreased kidney function and to dialytic therapies, occasionally leading to spontaneous resolution of hyperglycemia and normalization of hemoglobin A1c levels, a condition which might be termed “burnt-out diabetes”. Further difficulties in ESRD are posed by the complicated pharmacokinetics of antidiabetic medications and the serious flaws in our available diagnostic tools used for monitoring long-term glycemic control. We review the physiology and pathophysiology of glucose homeostasis in advanced CKD and ESRD, the available antidiabetic medications and their specifics related to kidney function, and the diagnostic tools used to monitor the severity of hyperglycemia and the therapeutic effects of available treatments, along with their deficiencies in ESRD. We also review the concept of burnt-out diabetes and summarize the findings of studies that examined outcomes related to glycemic control in diabetic ESRD patients, and emphasize areas in need of further research. PMID:20374552

Monitoring high-intensity focused ultrasound (HIFU) therapy using radio frequency ultrasound backscatter to quantify heating

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay

2005-09-01

The spatial distribution and temporal history of tissue temperature is an essential indicator of thermal therapy progress, and treatment safety and efficacy. Magnetic resonance methods provide the gold standard noninvasive measurement of temperature but are costly and cumbersome compared to the therapy itself. We have been developing the use of ultrasound backscattering for real-time temperature estimation; ultrasonic methods have been limited to relatively low temperature rise, primarily due to lack of sensitivity at protein denaturation temperatures (50-70°C). Through validation experiments on gel phantoms and ex vivo tissue we show that temperature rise can be accurately mapped throughout the therapeutic temperature range using a new BioHeat Transfer Equation (BHTE) model-constrained inverse approach. Speckle-free temperature and thermal dose maps are generated using the ultrasound calibrated model over the imaged region throughout therapy delivery and post-treatment cooling periods. Results of turkey breast tissue experiments are presented for static HIFU exposures, in which the ultrasound calibrated BHTE temperature maps are shown to be very accurate (within a degree) using independent thermocouple measurements. This new temperature monitoring method may speed clinical adoption of ultrasound-guided HIFU therapy. [Work supported by Army MRMC.

The World Health Organization's Response to Emerging Human Immunodeficiency Virus Drug Resistance and a Call for Global Action.

PubMed

Bertagnolio, Silvia; Beanland, Rachel L; Jordan, Michael R; Doherty, Meg; Hirnschall, Gottfried

2017-12-01

The global community, including the World Health Organization (WHO), has committed to ending the AIDS epidemic and to ensuring that 90% of people living with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and 90% achieve and maintain virological suppression. The emergence of HIV drug resistance (HIVDR) as antiretroviral treatment programs expand could preclude the 90-90-90 targets adopted by the United Nations General Assembly at the High-Level Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a call for collective action grounded on normative guidance providing a standardized and robust approach to monitoring, preventing, and responding to HIVDR over the next 5 years (2017-2021). WHO is committed to supporting country, global, regional, and national partners to implement and monitor the progress of the Global Action Plan. This article outlines the key components of WHO's strategy to tackle HIVDR and the role the organization takes in leading the global response to HIVDR. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The Comprehensive, Powerful, Academic Database (CPAD): An Evaluative Study of a Predictive Tool Designed for Elementary School Personnel in Identifying At-Risk Students through Progress, Curriculum, and Performance Monitoring

ERIC Educational Resources Information Center

Chavez-Gibson, Sarah

2013-01-01

The purpose of this study is to exam in-depth, the Comprehensive, Powerful, Academic Database (CPAD), a data decision-making tool that determines and identifies students at-risk of dropping out of school, and how the CPAD assists administrators and teachers at an elementary campus to monitor progress, curriculum, and performance to improve student…

Advancing Stage 2 Research on Measures for Monitoring Kindergarten Reading Progress.

PubMed

Clemens, Nathan H; Soohoo, Michelle M; Wiley, Colby P; Hsiao, Yu-Yu; Estrella, Ivonne; Allee-Smith, Paula J; Yoon, Myeongsun

Although several measures exist for frequently monitoring early reading progress, little research has specifically investigated their technical properties when administered on a frequent basis with kindergarten students. In this study, kindergarten students ( N = 137) of whom the majority was receiving supplemental intervention for reading skills were monitored using Letter Sound Fluency, Phoneme Segmentation Fluency, Word Reading Fluency, Nonsense Word Fluency, Highly Decodable Passages, and Spelling on a biweekly basis between February and May. Acceptable reliability was observed for all measures. Analyses of slope validity using latent growth models, latent change score models, and slope differences according to level of year-end achievement indicated that the relation of slope to overall reading skills varied across the measures. A suggested approach to kindergarten students' reading progress is offered that includes Letter Sound Fluency and a measure of word-reading skills to provide a comprehensive picture of student growth toward important year-end reading outcomes.

Data Fusion Tool for Spiral Bevel Gear Condition Indicator Data

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Antolick, Lance J.; Branning, Jeremy S.; Thomas, Josiah

2014-01-01

Tests were performed on two spiral bevel gear sets in the NASA Glenn Spiral Bevel Gear Fatigue Test Rig to simulate the fielded failures of spiral bevel gears installed in a helicopter. Gear sets were tested until damage initiated and progressed on two or more gear or pinion teeth. During testing, gear health monitoring data was collected with two different health monitoring systems. Operational parameters were measured with a third data acquisition system. Tooth damage progression was documented with photographs taken at inspection intervals throughout the test. A software tool was developed for fusing the operational data and the vibration based gear condition indicator (CI) data collected from the two health monitoring systems. Results of this study illustrate the benefits of combining the data from all three systems to indicate progression of damage for spiral bevel gears. The tool also enabled evaluation of the effectiveness of each CI with respect to operational conditions and fault mode.

Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

PubMed

Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

2018-01-01

The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Biomarkers in patients treated with BCG: an update.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

Kidney volume measurement methods for clinical studies on autosomal dominant polycystic kidney disease

PubMed Central

Sharma, Kanishka; Caroli, Anna; Quach, Le Van; Petzold, Katja; Bozzetto, Michela; Serra, Andreas L.; Remuzzi, Giuseppe; Remuzzi, Andrea

2017-01-01

Background In autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is regarded as an important biomarker of disease progression and different methods are available to assess kidney volume. The purpose of this study was to identify the most efficient kidney volume computation method to be used in clinical studies evaluating the effectiveness of treatments on ADPKD progression. Methods and findings We measured single kidney volume (SKV) on two series of MR and CT images from clinical studies on ADPKD (experimental dataset) by two independent operators (expert and beginner), twice, using all of the available methods: polyline manual tracing (reference method), free-hand manual tracing, semi-automatic tracing, Stereology, Mid-slice and Ellipsoid method. Additionally, the expert operator also measured the kidney length. We compared different methods for reproducibility, accuracy, precision, and time required. In addition, we performed a validation study to evaluate the sensitivity of these methods to detect the between-treatment group difference in TKV change over one year, using MR images from a previous clinical study. Reproducibility was higher on CT than MR for all methods, being highest for manual and semiautomatic contouring methods (planimetry). On MR, planimetry showed highest accuracy and precision, while on CT accuracy and precision of both planimetry and Stereology methods were comparable. Mid-slice and Ellipsoid method, as well as kidney length were fast but provided only a rough estimate of kidney volume. The results of the validation study indicated that planimetry and Stereology allow using an importantly lower number of patients to detect changes in kidney volume induced by drug treatment as compared to other methods. Conclusions Planimetry should be preferred over fast and simplified methods for accurately monitoring ADPKD progression and assessing drug treatment effects. Expert operators, especially on MR images, are required for performing reliable estimation of kidney volume. The use of efficient TKV quantification methods considerably reduces the number of patients to enrol in clinical investigations, making them more feasible and significant. PMID:28558028

Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials.

PubMed

Dedania, Vaidehi S; Liu, Jerry Y; Schlegel, Dana; Andrews, Chris A; Branham, Kari; Khan, Naheed W; Musch, David C; Heckenlively, John R; Jayasundera, K Thiran

2018-01-01

Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm 2 (I4e, p = 0.012), 720 ± 155 mm 2 (III4e, p < 0.001), and 759 ± 167 mm 2 (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm 2 (I4e), 9379 mm 2 (III4e), and 10346 mm 2 (IV4e), indicating a large variability. At 2.5 years after the baseline GVF the area increased ≥ 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

Budget impact of everolimus for the treatment of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic.

PubMed

Rose, Darya B; Nellesen, Dave; Neary, Maureen P; Cai, Beilei

2017-04-01

Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic. To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs. Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs. In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568-$0.1443 per member per month (PMPM) for GI NETs and from $0.0181-$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies). Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results. The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.

Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

PubMed

Pritchard, Kathleen I; Burris, Howard A; Ito, Yoshinori; Rugo, Hope S; Dakhil, Shaker; Hortobagyi, Gabriel N; Campone, Mario; Csöszi, Tibor; Baselga, José; Puttawibul, Puttisak; Piccart, Martine; Heng, Daniel; Noguchi, Shinzaburo; Srimuninnimit, Vichien; Bourgeois, Hugues; Gonzalez Martin, Antonio; Osborne, Karen; Panneerselvam, Ashok; Taran, Tetiana; Sahmoud, Tarek; Gnant, Michael

2013-12-01

Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

24 CFR 598.620 - Evaluation, monitoring, and enforcement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES URBAN EMPOWERMENT ZONES: ROUND TWO AND THREE DESIGNATIONS Empowerment Zone Grants § 598.620 Evaluation, monitoring, and enforcement. (a) Progress...