Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds

PubMed Central

2013-01-01

Background Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. Results The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. Conclusions EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well. PMID:23452300

Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds.

PubMed

Lewis, Thomas W; Blott, Sarah C; Woolliams, John A

2013-03-02

Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well.

Chronic progressive lymphoedema in draught horses.

PubMed

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.

A Third Reason to Home School: Leadership Development

ERIC Educational Resources Information Center

Seago, Johnnie

2012-01-01

This article responds to Poutiatine's (2009) "What is Transformational?: Nine Principles Toward an Understanding Transformational Process for Transformational Leadership" by relating home schooling environments as lab schools for developing transformational leaders. Although many families select home schooling for improved academic progress or…

Improved design of prodromal Alzheimer's disease trials through cohort enrichment and surrogate endpoints.

PubMed

Macklin, Eric A; Blacker, Deborah; Hyman, Bradley T; Betensky, Rebecca A

2013-01-01

Alzheimer's disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: 1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and 2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n = 358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n = 6,243). To identify a "mid-risk" subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases.

Improved design of prodromal Alzheimer’s disease trials through cohort enrichment and surrogate endpoints

PubMed Central

Macklin, Eric A.; Blacker, Deborah; Hyman, Bradley T.; Betensky, Rebecca A.

2013-01-01

Summary Alzheimer’s disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: (1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and (2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n=358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n=6,243). To identify a “mid-risk” subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases. PMID:23629586

A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

PubMed Central

Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

2015-01-01

The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

Ceramic technology for automotive turbines

NASA Technical Reports Server (NTRS)

Mclean, A. F.

1982-01-01

The paper presents an update on ceramic technology for automotive turbines. Progress in research and development of improved ceramics is reviewed, including approaches for assessing time-dependent strength characteristics. Processes for making shapes are discussed, and the design and testing of selected ceramic turbine components are reviewed.

Proven in vitro evolution of protease cathepsin E-inhibitors and -activators at pH 4.5 using a paired peptide method.

PubMed

Kitamura, Koichiro; Komatsu, Masayuki; Biyani, Madhu; Futakami, Masae; Kawakubo, Tomoyo; Yamamoto, Kenji; Nishigaki, Koichi

2012-12-01

Improving a particular function of molecules is often more difficult than identifying such molecules ab initio. Here, a method to acquire higher affinity and/or more functional peptides was developed as a progressive library selection method. The primary library selection products were utilized to build a secondary library composed of blocks of 4 amino acids, of which selection led to peptides with increased activity. These peptides were further converted to randomly generate paired peptides. Cathepsin E-inhibitors thus obtained exhibited the highest activities and affinities (pM order). This was also the case with cathepsin E-activating peptides, proving the methodological effectiveness. The primary, secondary, and tertiary library selections can be regarded as module-finding, module-shuffling, and module-pairing, respectively, which resembles the progression of the natural evolution of proteins. The mode of peptide binding to their target proteins is discussed in analogy to antibodies and epitopes of an antigen. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Genetic Insights in Barrett’s Esophagus and Esophageal Adenocarcinoma

PubMed Central

Reid, Brian J.; Paulson, Thomas G.; Li, Xiaohong

2015-01-01

Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett’s esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine “windows of opportunity” in time to detect rapidly progressing BE and distinguish it from slowly or non-progressing BE. PMID:26208895

Progress Report on the Improved Linear Ion Trap Physics Package

NASA Technical Reports Server (NTRS)

Prestage, John D.

1995-01-01

This article describes the first operational results from the extended linear ion trap frequency standard now being developed at JPL. This new design separates the state selection/interrogation region from the more critical microwave resonance region where the multiplied local oscillator (LO) signal is compared to the stable atomic transition. Hg+ ions have been trapped, shuttled back and forth between the resonance and state selection traps. In addition, microwave transitions between the Hg+ clock levels have been driven in the resonance trap and detected in the state selection trap.

Program review presentation to Level 1, Interagency Coordination Committee

NASA Technical Reports Server (NTRS)

1982-01-01

Progress in the development of crop inventory technology is reported. Specific topics include the results of a thematic mapper analysis, variable selection studies/early season estimator improvements, the agricultural information system simulator, large unit proportion estimation, and development of common features for multi-satellite information extraction.

A study on operation efficiency evaluation based on firm's financial index and benchmark selection: take China Unicom as an example

NASA Astrophysics Data System (ADS)

Wu, Zu-guang; Tian, Zhan-jun; Liu, Hui; Huang, Rui; Zhu, Guo-hua

2009-07-01

Being the only listed telecom operators of A share market, China Unicom has always been attracted many institutional investors under the concept of 3G recent years,which itself is a great technical progress expectation.Do the institutional investors or the concept of technical progress have signficant effect on the improving of firm's operating efficiency?Though reviewing the documentary about operating efficiency we find that schoolars study this problem useing the regress analyzing based on traditional production function and data envelopment analysis(DEA) and financial index anayzing and marginal function and capital labor ratio coefficient etc. All the methods mainly based on macrodata. This paper we use the micro-data of company to evaluate the operating efficiency.Using factor analyzing based on financial index and comparing the factor score of three years from 2005 to 2007, we find that China Unicom's operating efficiency is under the averge level of benchmark corporates and has't improved under the concept of 3G from 2005 to 2007.In other words,institutional investor or the conception of technical progress expectation have faint effect on the changes of China Unicom's operating efficiency. Selecting benchmark corporates as post to evaluate the operating efficiency is a characteristic of this method ,which is basicallly sipmly and direct.This method is suit for the operation efficiency evaluation of agriculture listed companies because agriculture listed also face technical progress and marketing concept such as tax-free etc.

Getting right to the point: identifying Australian outpatients' priorities and preferences for patient-centred quality improvement in chronic disease care.

PubMed

Fradgley, Elizabeth A; Paul, Christine L; Bryant, Jamie; Oldmeadow, Christopher

2016-09-01

To identify specific actions for patient-centred quality improvement in chronic disease outpatient settings, this study identified patients' general and specific preferences among a comprehensive suite of initiatives for change. A cross-sectional survey was conducted in three hospital-based clinics specializing in oncology, neurology and cardiology care located in New South Wales, Australia. Adult English-speaking outpatients completed the touch-screen Consumer Preferences Survey in waiting rooms or treatment areas. Participants selected up to 23 general initiatives that would improve their experience. Using adaptive branching, participants could select an additional 110 detailed initiatives and complete a relative prioritization exercise. A total of 541 individuals completed the survey (71.1% consent, 73.1% completion). Commonly selected general initiatives, presented in order of decreasing priority (along with sample proportion), included: improved parking (60.3%), up-to-date information provision (15.0%), ease of clinic contact (12.9%), access to information at home (12.8%), convenient appointment scheduling (14.2%), reduced wait-times (19.8%) and information on medical emergencies (11.1%). To address these general initiatives, 40 detailed initiatives were selected by respondents. Initiatives targeting service accessibility and information provision, such as parking and up-to-date information on patient prognoses and progress, were commonly selected and perceived to be of relatively greater priority. Specific preferences included the need for clinics to provide patient-designated parking in close proximity to the clinic, information on treatment progress and test results (potentially in the form of designated brief appointments or via telehealth) and comprehensive and trustworthy lists of information sources to access at home. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pseudo progression identification of glioblastoma with dictionary learning.

PubMed

Zhang, Jian; Yu, Hengyong; Qian, Xiaohua; Liu, Keqin; Tan, Hua; Yang, Tielin; Wang, Maode; Li, King Chuen; Chan, Michael D; Debinski, Waldemar; Paulsson, Anna; Wang, Ge; Zhou, Xiaobo

2016-06-01

Although the use of temozolomide in chemoradiotherapy is effective, the challenging clinical problem of pseudo progression has been raised in brain tumor treatment. This study aims to distinguish pseudo progression from true progression. Between 2000 and 2012, a total of 161 patients with glioblastoma multiforme (GBM) were treated with chemoradiotherapy at our hospital. Among the patients, 79 had their diffusion tensor imaging (DTI) data acquired at the earliest diagnosed date of pseudo progression or true progression, and 23 had both DTI data and genomic data. Clinical records of all patients were kept in good condition. Volumetric fractional anisotropy (FA) images obtained from the DTI data were decomposed into a sequence of sparse representations. Then, a feature selection algorithm was applied to extract the critical features from the feature matrix to reduce the size of the feature matrix and to improve the classification accuracy. The proposed approach was validated using the 79 samples with clinical DTI data. Satisfactory results were obtained under different experimental conditions. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.87 for a given dictionary with 1024 atoms. For the subgroup of 23 samples, genomics data analysis was also performed. Results implied further perspective on pseudo progression classification. The proposed method can determine pseudo progression and true progression with improved accuracy. Laboring segmentation is no longer necessary because this skillfully designed method is not sensitive to tumor location. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accelerated Reader™. What Works Clearinghouse Intervention Report. Updated

ERIC Educational Resources Information Center

What Works Clearinghouse, 2016

2016-01-01

Accelerated Reader™ is a computerized supplementary reading program that provides guided reading instruction to students in grades K-12. It aims to improve students' reading skills through reading practice and by providing frequent feedback on students' progress to teachers. The Accelerated Reader™ program requires students to select and read a…

PROGRESSIVE MUSCULAR DYSTROPHY—A Preliminary Report on Treatment with Amino Acids, Folic Acid and Vitamins

PubMed Central

Van Meter, J. Ray

1953-01-01

Ten patients with progressive muscular dystrophy were given daily oral doses of amino acids, folic acid and selected vitamins. At the time of this report they had been treated by this means for periods varying from two months to one year. Only one had other therapy concurrently. Definite and progressive improvement, objective and subjective, occurred in all cases. Among objective changes noted—not all of them in all cases—were return of strength, increase in size and tonus of atrophic muscles, restoration of normal respiratory action and relief of depression. Patients reported a sense of well-being, increase in strength and a feeling of bodily warmth. PMID:13094541

Epigenetic Regulation in Prostate Cancer Progression.

PubMed

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Modeling Tumor Clonal Evolution for Drug Combinations Design.

PubMed

Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

2016-03-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs.

Essential Medicine Utilization and Situation in Selected Ten Developing Countries: A Compendious Audit

PubMed Central

Haque, Mainul

2017-01-01

Medicine improves the quality of life and increases mean age of human beings as it fights against diseases. Accessibility to medicines is the fundamental right of every person. The principle of the essential medicines (EMs) is that a limited number of availability of medicine will promote to a better supply chain and rational prescribing to the rural and remote health centers for any developing countries. Furthermore, it was also expected that this concept will also ensure better procurement policy at lower costs, more in amount, with easier storage. Thereby, EMs will safeguard and improve distribution and dispensing of medicine. Correspondingly, motivational and dedicated training program regarding drug information and adverse drug reactions will boost up access to medicine and health-care. In addition, the selection of medicine from EM is the first step in the direction of the rational use of medicine and progress and ensuring the quality of health care. Thereafter, selection needs to be followed by appropriate use. Everyone should receive the right medicine, in an adequate dose for an adequate duration, with appropriate information and follow-up treatment, and at an affordable cost. The acceptance and implementation of World Health Organization-promoted EM policies in deferent countries have improved quality use of medicine in terms of accessibility and affordability, predominantly in developing countries. The corporations and teamwork among various participants of health care are instantly obligatory to progress equitable access to medicines in low- and middle-income countries. PMID:28852629

Closing the Gap: An Overview. The Achievement Gap: An Overview. Info Brief. Number 44

ERIC Educational Resources Information Center

Poliakoff, Anne Rogers

2006-01-01

Persistent gaps between the academic achievements of different groups of children are thoroughly documented by the U.S. National Assessment of Educational Progress and other statistical analyses of state assessments, grades, course selection, and dropout rates. Despite improvements in some years, the gap endures as a consistent and disturbing…

Unilateral lung transplantation for pulmonary fibrosis.

PubMed

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

Analysis of signal to noise enhancement using a highly selective modulation tracking filter

NASA Technical Reports Server (NTRS)

Haden, C. R.; Alworth, C. W.

1972-01-01

Experiments are reported which utilize photodielectric effects in semiconductor loaded superconducting resonant circuits for suppressing noise in RF communication systems. The superconducting tunable cavity acts as a narrow band tracking filter for detecting conventional RF signals. Analytical techniques were developed which lead to prediction of signal-to-noise improvements. Progress is reported in optimization of the experimental variables. These include improved Q, new semiconductors, improved optics, and simplification of the electronics. Information bearing signals were passed through the system, and noise was introduced into the computer model.

High-response hybrid quantum dots- 2D conductor phototransistors: recent progress and perspectives

NASA Astrophysics Data System (ADS)

Sablon, Kimberly A.; Sergeev, Andrei; Najmaei, Sina; Dubey, Madan

2017-03-01

Having been inspired by the tremendous progress in material nanoscience and device nanoengineering, hybrid phototransistors combine solution processed colloidal semiconductor quantum dots (QDs) with graphene or two-dimensional (2D) semiconductor materials. Novel detectors demonstrate ultrahigh photoconductive gain, high and selective photoresponse, low noise, and very high responsivity in visible- and near-infrared ranges. The outstanding performance of phototransistors is primarily due to the strong, selective, and size tunable absorption of QDs and fast charge transfer in 2D high mobility conductors. However, the relatively small mobility of QD nanomaterials was a technological barrier, which limited the operating rate of devices. Very recent innovations in detector design and significant progress in QD ligand engineering provide effective tools for further qualitative improvements. This article reviews the recent progress in material science, nanophysics, and device engineering related to hybrid phototransistors. Detectors based on various QD nanomaterials and several 2D conductors are compared, and advantages and disadvantages of various nanomaterials for applications in hybrid phototransistors are identified. We also benchmark the experimental characteristics with model results that establish interrelations and tradeoffs between detector characteristics, such as responsivity, dark and noise currents, the photocarrier lifetime, response, and noise bandwidths. We have shown that the most recent phototransistors demonstrate performance limited by the fundamental generation recombination noise in high gain devices. Interrelation between the dynamic range of the detector and the detector sensitivity is discussed. The review is concluded with a brief discussion of the remaining challenges and possible significant improvements in the performance of hybrid phototransistors.

Induced Mutations for Improving Production on Bread and Durum Wheat

NASA Astrophysics Data System (ADS)

Stamo, Ilirjana; Ylli, Ariana; Dodbiba, Andon

2007-04-01

Wheat is a very important crop and has been bred for food and its improvement is continuous from cross-breeding. Radiation and chemically induced mutations have provided variability in selection for novel varieties. Four bread and one durum wheat cultivars were exposed to gamma rays, Cs 137 with doses 10, 15 and 20 krad (2000 seeds of each dose and cultivars). We have isolated mutant plants with height reduced and on cv Progress spike without chaff.

Induced Mutations for Improving Production on Bread and Durum Wheat

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

Stamo, Ilirjana; Ylli, Ariana; Dodbiba, Andon

Wheat is a very important crop and has been bred for food and its improvement is continuous from cross-breeding. Radiation and chemically induced mutations have provided variability in selection for novel varieties. Four bread and one durum wheat cultivars were exposed to gamma rays, Cs 137 with doses 10, 15 and 20 krad (2000 seeds of each dose and cultivars). We have isolated mutant plants with height reduced and on cv Progress spike without chaff.

Development and application of biological technologies in fish genetic breeding.

PubMed

Xu, Kang; Duan, Wei; Xiao, Jun; Tao, Min; Zhang, Chun; Liu, Yun; Liu, ShaoJun

2015-02-01

Fish genetic breeding is a process that remolds heritable traits to obtain neotype and improved varieties. For the purpose of genetic improvement, researchers can select for desirable genetic traits, integrate a suite of traits from different donors, or alter the innate genetic traits of a species. These improved varieties have, in many cases, facilitated the development of the aquaculture industry by lowering costs and increasing both quality and yield. In this review, we present the pertinent literatures and summarize the biological bases and application of selection breeding technologies (containing traditional selective breeding, molecular marker-assisted breeding, genome-wide selective breeding and breeding by controlling single-sex groups), integration breeding technologies (containing cross breeding, nuclear transplantation, germline stem cells and germ cells transplantation, artificial gynogenesis, artificial androgenesis and polyploid breeding) and modification breeding technologies (represented by transgenic breeding) in fish genetic breeding. Additionally, we discuss the progress our laboratory has made in the field of chromosomal ploidy breeding of fish, including distant hybridization, gynogenesis, and androgenesis. Finally, we systematically summarize the research status and known problems associated with each technology.

Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

PubMed Central

Colihueque, Nelson; Araneda, Cristian

2014-01-01

Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

Advances in medical image computing.

PubMed

Tolxdorff, T; Deserno, T M; Handels, H; Meinzer, H-P

2009-01-01

Medical image computing has become a key technology in high-tech applications in medicine and an ubiquitous part of modern imaging systems and the related processes of clinical diagnosis and intervention. Over the past years significant progress has been made in the field, both on methodological and on application level. Despite this progress there are still big challenges to meet in order to establish image processing routinely in health care. In this issue, selected contributions of the German Conference on Medical Image Processing (BVM) are assembled to present latest advances in the field of medical image computing. The winners of scientific awards of the German Conference on Medical Image Processing (BVM) 2008 were invited to submit a manuscript on their latest developments and results for possible publication in Methods of Information in Medicine. Finally, seven excellent papers were selected to describe important aspects of recent advances in the field of medical image processing. The selected papers give an impression of the breadth and heterogeneity of new developments. New methods for improved image segmentation, non-linear image registration and modeling of organs are presented together with applications of image analysis methods in different medical disciplines. Furthermore, state-of-the-art tools and techniques to support the development and evaluation of medical image processing systems in practice are described. The selected articles describe different aspects of the intense development in medical image computing. The image processing methods presented enable new insights into the patient's image data and have the future potential to improve medical diagnostics and patient treatment.

Modeling Tumor Clonal Evolution for Drug Combinations Design

PubMed Central

Zhao, Boyang; Hemann, Michael T.; Lauffenburger, Douglas A.

2016-01-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs. PMID:28435907

Progress in multidisciplinary design optimization at NASA Langley

NASA Technical Reports Server (NTRS)

Padula, Sharon L.

1993-01-01

Multidisciplinary Design Optimization refers to some combination of disciplinary analyses, sensitivity analysis, and optimization techniques used to design complex engineering systems. The ultimate objective of this research at NASA Langley Research Center is to help the US industry reduce the costs associated with development, manufacturing, and maintenance of aerospace vehicles while improving system performance. This report reviews progress towards this objective and highlights topics for future research. Aerospace design problems selected from the author's research illustrate strengths and weaknesses in existing multidisciplinary optimization techniques. The techniques discussed include multiobjective optimization, global sensitivity equations and sequential linear programming.

Single-layer centrifugation through PureSperm® 80 selects improved quality spermatozoa from frozen-thawed dog semen.

PubMed

Dorado, J; Alcaraz, L; Gálvez, M J; Acha, D; Ortiz, I; Urbano, M; Hidalgo, M

2013-08-01

The aim of this study was to investigate whether single-layer centrifugation (SLC) with PureSperm® 80 could select good quality spermatozoa, including those with specific motility patterns, from doses of frozen dog semen. Semen from 5 dogs was collected and cryopreserved following a standard protocol. After thawing, semen samples were divided into two aliquots: one of them was used as control and the other one processed by SLC. Assessment of sperm motility (assessed by computer-assisted semen analysis), morphology (Diff-Quick staining) and viability (triple fluorescent stain of propidium iodine/isothiocyanate-labeled peanut (Arachis hypogaea) agglutinin/Rhodamine 123), were performed on aliquots of fresh semen, frozen-thawed control and frozen-thawed SLC treated samples. A multivariate clustering procedure separated 26,051 motile spermatozoa into three subpopulations (sP): sP1 consisting of highly active but non-progressive spermatozoa (40.3%), sP2 consisting of spermatozoa with high velocity and progressive motility (30.0%), and sP3 consisting of poorly active and non-progressive spermatozoa (29.7%). SLC with PureSperm® 80 yielded sperm suspensions with improved motility, morphology, viability and acrosome integrity (P<0.001). The frozen-thawed SLC treated samples were enriched in sP2, reaching a proportion of 44.1% of the present spermatozoa. From these results, we concluded that SLC with PureSperm® 80 may be an alternative and successful method for improving the quality of frozen-thawed dog spermatozoa. Moreover, sP2 (high-speed and progressive spermatozoa) was more frequently observed after SLC. Finally, this study also demonstrated that the general motile sperm structure present in dogs remained constant despite the effect caused by either cryopreservation or separation by SLC through PureSperm® 80. Copyright © 2013 Elsevier B.V. All rights reserved.

Focus. Volume 27, Number 2, Winter 2010

ERIC Educational Resources Information Center

Caspar, Emma, Ed.

2010-01-01

The purpose of "Focus" is to provide coverage of poverty-related research, events, and issues, and to acquaint a large audience with the work of the Institute for Research on Poverty by means of short essays on selected pieces of research. This issue contains the following articles: (1) Progress toward Improving the U.S. Poverty Measure:…

The Need To Improve Language Arts Education by Means of Esperanto.

ERIC Educational Resources Information Center

Jones, R. Kent

Education helps children select and progress toward appropriate goals. One of the impediments to education for American students is their lack of skill in English. Clear insight into the essentials of language comes from observing how the variables function in a model language such as Esperanto. Once children understand the basic anatomy of…

Hepatitis C and liver transplantation

NASA Astrophysics Data System (ADS)

Brown, Robert S.

2005-08-01

Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

Minimal ensemble based on subset selection using ECG to diagnose categories of CAN.

PubMed

Abawajy, Jemal; Kelarev, Andrei; Yi, Xun; Jelinek, Herbert F

2018-07-01

Early diagnosis of cardiac autonomic neuropathy (CAN) is critical for reversing or decreasing its progression and prevent complications. Diagnostic accuracy or precision is one of the core requirements of CAN detection. As the standard Ewing battery tests suffer from a number of shortcomings, research in automating and improving the early detection of CAN has recently received serious attention in identifying additional clinical variables and designing advanced ensembles of classifiers to improve the accuracy or precision of CAN diagnostics. Although large ensembles are commonly proposed for the automated diagnosis of CAN, large ensembles are characterized by slow processing speed and computational complexity. This paper applies ECG features and proposes a new ensemble-based approach for diagnosis of CAN progression. We introduce a Minimal Ensemble Based On Subset Selection (MEBOSS) for the diagnosis of all categories of CAN including early, definite and atypical CAN. MEBOSS is based on a novel multi-tier architecture applying classifier subset selection as well as the training subset selection during several steps of its operation. Our experiments determined the diagnostic accuracy or precision obtained in 5 × 2 cross-validation for various options employed in MEBOSS and other classification systems. The experiments demonstrate the operation of the MEBOSS procedure invoking the most effective classifiers available in the open source software environment SageMath. The results of our experiments show that for the large DiabHealth database of CAN related parameters MEBOSS outperformed other classification systems available in SageMath and achieved 94% to 97% precision in 5 × 2 cross-validation correctly distinguishing any two CAN categories to a maximum of five categorizations including control, early, definite, severe and atypical CAN. These results show that MEBOSS architecture is effective and can be recommended for practical implementations in systems for the diagnosis of CAN progression. Copyright © 2018 Elsevier B.V. All rights reserved.

Understanding Mechanisms of Resistance in the Epithelial Growth Factor Receptor in Non‐Small Cell Lung Cancer and the Role of Biopsy at Progression

PubMed Central

Villaruz, Liza C.; Ross, Jeffrey

2016-01-01

Abstract Molecular profiling and the discovery of drugs that target specific activating mutations have allowed the personalization of treatment for non‐small cell lung cancer (NSCLC). The epithelial growth factor receptor (EGFR) is frequently over‐expressed and/or aberrantly activated in different cancers, including NSCLC. The most common activating mutations of EGFR in NSCLC fall within the tyrosine kinase‐binding domain. Three oral EGFR tyrosine kinase inhibitors (TKIs) have been approved by the U.S. Food and Drug Administration (FDA) for first‐line use in patients with EGFR mutation‐positive NSCLC (exon 19 deletions or exon 21 [L858R] substitution mutations), as detected by an FDA‐approved test. However, disease progression is common and is often the result of secondary mutations, of which the EGFR T790M mutation is the most prevalent. Few options were available upon progression until the introduction of osimertinib, a kinase inhibitor that targets the T790M mutation, which was recently approved for use in patients with metastatic EGFR T790M mutation‐positive NSCLC, as detected by an FDA‐approved test, who progressed on or after EGFR TKI therapy. With the introduction of osimertinib, outcomes can now be improved in select patients. Therefore, performing a biopsy at progression to determine the underlying molecular cause of the acquired resistance is important for the enabling of individualized options that may provide the greatest opportunity for improved outcomes. This review discusses the latest updates in molecular testing at progression and outlines treatment options for this difficult‐to‐treat population. Implications for Practice. Although the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)—gefitinib, erlotinib, and afatinib—have changed the treatment paradigm for non‐small cell lung cancer among those with EGFR mutation positive disease, most patients experience progression after approximately 12 months of treatment. Until recently, options were limited for patients who progressed, but improvements in molecular profiling and the approval of osimertinib, which targets the resistance mutation T790M, afford the opportunity for improved outcomes in many patients with this mutation. This article explains the options available after progression on initial EGFR TKI therapy and the importance of molecular testing at progression in making treatment decisions. PMID:27821794

Long-term on-farm participatory maize breeding by stratified mass selection retains molecular diversity while improving agronomic performance.

PubMed

Alves, Mara Lisa; Belo, Maria; Carbas, Bruna; Brites, Cláudia; Paulo, Manuel; Mendes-Moreira, Pedro; Brites, Carla; Bronze, Maria do Rosário; Šatović, Zlatko; Vaz Patto, Maria Carlota

2018-02-01

Modern maize breeding programs gave rise to genetically uniform varieties that can affect maize's capacity to cope with increasing climate unpredictability. Maize populations, genetically more heterogeneous, can evolve and better adapt to a broader range of edaphic-climatic conditions. These populations usually suffer from low yields; it is therefore desirable to improve their agronomic performance while maintaining their valuable diversity levels. With this objective, a long-term participatory breeding/on-farm conservation program was established in Portugal. In this program, maize populations were subject to stratified mass selection. This work aimed to estimate the effect of on-farm stratified mass selection on the agronomic performance, quality, and molecular diversity of two historical maize populations. Multilocation field trials, comparing the initial populations with the derived selection cycles, showed that this selection methodology led to agronomic improvement for one of the populations. The molecular diversity analysis, using microsatellites, revealed that overall genetic diversity in both populations was maintained throughout selection. The comparison of quality parameters between the initial populations and the derived selection cycles was made using kernel from a common-garden experiment. This analysis showed that the majority of the quality traits evaluated progressed erratically over time. In conclusion, this breeding approach, through simple and low-cost methodologies, proved to be an alternative strategy for genetic resources' on-farm conservation.

The new wave of ion-selective electrodes

PubMed Central

Pretsch, Ernö

2007-01-01

During the last decade, the capabilities of potentiometric analysis have changed fundamentally in that the lower limit of detection (LOD) of ion-selective electrodes (ISEs) has improved by a factor of up to one million and the discrimination factor of interferences from ions by up to one billion. These spectacular improvements are related to the control of ion fluxes through the ion-selective membrane. Nowadays, ISEs can be used for trace measurements in environmental samples. However, by reducing the volume of the samples, the LOD in terms of the amount of analytes has been reduced to the attomole range. This is promising for bioanalysis using metal nanoparticle labels. Other recent progress includes the excellent fundamental understanding of the working mechanism, the introduction of a novel kind of calibration procedure that reduces the demands on signal stability and reproducibility, and the advent of pulsed amperometric methods. PMID:12175191

Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients.

PubMed

Ahola, Sofia; Auranen, Mari; Isohanni, Pirjo; Niemisalo, Satu; Urho, Niina; Buzkova, Jana; Velagapudi, Vidya; Lundbom, Nina; Hakkarainen, Antti; Muurinen, Tiina; Piirilä, Päivi; Pietiläinen, Kirsi H; Suomalainen, Anu

2016-11-01

Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1.5-2 weeks of diet, with progressive muscle pain and leakage of muscle enzymes, leading to premature discontinuation of the diet. Analysis of muscle ultrastructure revealed selective fiber damage, especially in the ragged-red-fibers (RRFs), a MM hallmark. Two years of follow-up showed improvement of muscle strength, suggesting activation of muscle regeneration. Our results indicate that (i) nutrition can modify mitochondrial disease progression, (ii) dietary counseling should be part of MM care, (iii) short mAD is a tool to induce targeted RRF lysis, and (iv) mAD, a common weight-loss method, may induce muscle damage in a population subgroup. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Exercise attenuates neuropathology and has greater benefit on cognitive than motor deficits in the R6/1 Huntington's disease mouse model.

PubMed

Harrison, David J; Busse, Monica; Openshaw, Rebecca; Rosser, Anne E; Dunnett, Stephen B; Brooks, Simon P

2013-10-01

Huntington's disease (HD) is a neurodegenerative disease caused by a mutation within the huntingtin gene that induces degeneration within the striatal nuclei, progressing to widespread brain atrophy and death. The neurodegeneration produces symptoms that reflect a corticostriatal disconnection syndrome involving motor, cognitive and psychiatric disturbance. Environmental enrichment has been demonstrated to be beneficial to patients with neurological disorders, with exercise being central to this effect. Rodent studies have confirmed exercise-induced neurogenesis and increased growth factor levels in the brain and improved behavioural function. The present study sought to determine whether an extended regime of exercise could retard disease progression in the R6/1 mouse model of HD. The study was designed specifically with a translational focus, selecting behavioural assessments with high clinical predictive validity. We found that exercise improved gait function in both control and HD mice and selectively improved performance in the R6/1 mice on a motor coordination aspect of the balance beam task. Exercise also retarded the progression of cognitive dysfunction on water T-maze procedural and reversal learning probes presented serially to probe cognitive flexibility. In addition, exercise reduced striatal neuron loss in the R6/1 mice but increased striatal neuronal intra-nuclear inclusion size and number relative to non-exercised R6/1 mice which demonstrated increased numbers of extra-neuronal inclusions, suggesting that the functional effects were striatally mediated. These results confirm and extend those from previous studies that demonstrate that HD may be amenable to exercise-mediated therapeutics, but suggest that the impact of such interventions may be primarily cognitive. © 2013.

In vivo selection to improve gene therapy of hematopoietic disorders.

PubMed

Persons, Derek A; Nienhuis, Arthur W

2002-10-01

Successful gene therapy of hematopoietic disorders lacking intrinsic natural selection for genetically corrected cells will require efficient ex vivo gene transfer into autologous hematopoietic stem cells (HSCs). For these diseases, currently available gene transfer methodologies are unlikely to result in therapeutic numbers of corrected HSCs, especially in the setting of minimal recipient conditioning. A strategy to increase the numbers of genetically corrected HSCs in an individual is therefore highly desirable. One approach to overcome the barrier of limiting numbers of genetically corrected cells is to endow them with a competitive advantage conferred by inclusion of a 'selectable' gene in the therapeutic vector. Herein, we review recent progress in the development of in vivo selection systems, which hold promise in facilitating successful gene therapy.

There is room for selection in a small local pig breed when using optimum contribution selection: a simulation study.

PubMed

Gourdine, J L; Sørensen, A C; Rydhmer, L

2012-01-01

Selection progress must be carefully balanced against the conservation of genetic variation in small populations of local breeds. Well-defined breeding programs with specified selection traits are rare in local pig breeds. Given the small population size, the focus is often on the management of genetic diversity. However, in local breeds, optimum contribution selection can be applied to control the rate of inbreeding and to avoid reduced performance in traits with high market value. The aim of this study was to assess the extent to which a breeding program aiming for improved product quality in a small local breed would be feasible. We used stochastic simulations to compare 25 scenarios. The scenarios differed in size of population, selection intensity of boars, type of selection (random selection, truncation selection based on BLUP breeding values, or optimum contribution selection based on BLUP breeding values), and heritability of the selection trait. It was assumed that the local breed is used in an extensive system for a high-meat-quality market. The simulations showed that in the smallest population (300 female reproducers), inbreeding increased by 0.8% when selection was performed at random. With optimum contribution selection, genetic progress can be achieved that is almost as great as that with truncation selection based on BLUP breeding values (0.2 to 0.5 vs. 0.3 to 0.5 genetic SD, P < 0.05), but at a considerably decreased rate of inbreeding (0.7 to 1.2 vs. 2.3 to 5.7%, P < 0.01). This confirmation of the potential utilization of OCS even in small populations is important in the context of sustainable management and the use of animal genetic resources.

[Watsu: a modern method in physiotherapy, body regeneration, and sports].

PubMed

Weber-Nowakowska, Katarzyna; Gebska, Magdalena; Zyzniewska-Banaszak, Ewelina

2013-01-01

Progress in existing methods of physiotherapy and body regeneration and introduction of new methods has made it possible to precisely select the techniques according to patient needs. The modern therapist is capable of improving the physical and mental condition of the patient. Watsu helps the therapist eliminate symptoms from the locomotor system and reach the psychic sphere at the same time.

Invited review: Current state of genetic improvement in dairy sheep.

PubMed

Carta, A; Casu, Sara; Salaris, S

2009-12-01

Dairy sheep have been farmed traditionally in the Mediterranean basin in southern Europe, central Europe, eastern Europe, and in Near East countries. Currently, dairy sheep farming systems vary from extensive to intensive according to the economic relevance of the production chain and the specific environment and breed. Modern breeding programs were conceived in the 1960s. The most efficient selection scheme for local dairy sheep breeds is based on pyramidal management of the population with the breeders of nucleus flocks at the top, where pedigree and official milk recording, artificial insemination, controlled natural mating, and breeding value estimation are carried out to generate genetic progress. The genetic progress is then transferred to the commercial flocks through artificial insemination or natural-mating rams. Increasing milk yield is still the most profitable breeding objective for several breeds. Almost all milk is used for cheese production and, consequently, milk content traits are very important. Moreover, other traits are gaining interest for selection: machine milking ability and udder morphology, resistance to diseases (mastitis, internal parasites, scrapie), and traits related to the nutritional value of milk (fatty acid composition). Current breeding programs based on the traditional quantitative approach have achieved appreciable genetic gains for milk yield. In many cases, further selection goals such as milk composition, udder morphology, somatic cell count, and scrapie resistance have been implemented. However, the possibility of including other traits of selective interest is limited by high recording costs. Also, the organizational effort needed to apply the traditional quantitative approach limits the diffusion of current selection programs outside the European Mediterranean area. In this context, the application of selection schemes assisted by molecular information, to improve either traditional dairy traits or traits costly to record, seems to be attractive in dairy sheep. At the moment, the most effective strategy seems to be the strengthening of research projects aimed at finding causal mutations along the genes affecting traits of economic importance. However, genome-wide selection seems to be unfeasible in most dairy sheep breeds.

A Robust Deep Model for Improved Classification of AD/MCI Patients

PubMed Central

Li, Feng; Tran, Loc; Thung, Kim-Han; Ji, Shuiwang; Shen, Dinggang; Li, Jiang

2015-01-01

Accurate classification of Alzheimer’s Disease (AD) and its prodromal stage, Mild Cognitive Impairment (MCI), plays a critical role in possibly preventing progression of memory impairment and improving quality of life for AD patients. Among many research tasks, it is of particular interest to identify noninvasive imaging biomarkers for AD diagnosis. In this paper, we present a robust deep learning system to identify different progression stages of AD patients based on MRI and PET scans. We utilized the dropout technique to improve classical deep learning by preventing its weight co-adaptation, which is a typical cause of over-fitting in deep learning. In addition, we incorporated stability selection, an adaptive learning factor, and a multi-task learning strategy into the deep learning framework. We applied the proposed method to the ADNI data set and conducted experiments for AD and MCI conversion diagnosis. Experimental results showed that the dropout technique is very effective in AD diagnosis, improving the classification accuracies by 5.9% on average as compared to the classical deep learning methods. PMID:25955998

[Charles Darwin and the problem of evolutionary progress].

PubMed

Iordanskiĭ, N N

2010-01-01

According to Ch. Darwin's evolutionary theory, evolutionary progress (interpreted as morpho-physiological progress or arogenesis in recent terminology) is one of logical results of natural selection. At the same time, natural selection does not hold any factors especially promoting evolutionary progress. Darwin emphasized that the pattern of evolutionary changes depends on organism nature more than on the pattern of environment changes. Arogenesis specificity is determined by organization of rigorous biological systems - integral organisms. Onward progressive development is determined by fundamental features of living organisms: metabolism and homeostasis. The concept of social Darwinism differs fundamentally from Darwin's ideas about the most important role of social instincts in progress of mankind. Competition and selection play secondary role in socio-cultural progress of human society.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials.

PubMed

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2018-03-14

Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Control of diabetes and fibrinogen levels as well as improvement in health care might delay low cognitive performance in societies aging progressively.

PubMed

Lopes, Daniele Almeida; Moraes, Suzana Alves de; Freitas, Isabel Cristina Martins de

2015-01-01

To know the prevalence and factors associated to low cognitive performance in a representative sample of the adult population in a society aging progressively. Cross-sectional population-based study carried out in a three-stage sampling: 81 census tracts (primary sampling unity) were randomly selected, followed by 1,672 households and 2,471 participants (weighted sample) corresponding to the second and third stages, respectively. The outcome prevalence was calculated according sociodemographic, behavioral and health related variables. Crude and adjusted prevalence ratios were estimated using Poisson regression. The prevalence of low cognitive performance was high, mainly among females, and indicated linear trends into categories of age, schooling, income, plasma fibrinogen and self-reported health status. In multivariate models, gender, diabetes, fibrinogen and self-reported health status presented positive associations, while schooling, employment and sitting time presented negative associations with the outcome. Interventions related to diabetes and fibrinogen levels control as well as improvement in health care might delay low cognitive performance in societies aging progressively as such the study population.

Applications of aerospace technology in the public interest: Pollution measurement

NASA Technical Reports Server (NTRS)

Heins, C. F.; Johnson, F. D.

1974-01-01

This study of selected NASA contributions to the improvement of pollution measurement examines the pervasiveness and complexity of the economic, political, and social issues in the environmental field; provides a perspective on the relationship between the conduct of aerospace R and D and specific improvements in on site air pollution monitoring equipment now in use; describes the basic relationship between the development of satellite-based monitoring systems and their influence on long-term progress in improving environmental quality; and comments on how both instrumentation and satellite remote sensing are contributing to an improved environment. Examples of specific gains that have been made in applying aerospace R and D to environmental problem-solving are included.

Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice.

PubMed

Langley, Monica; Ghosh, Anamitra; Charli, Adhithiya; Sarkar, Souvarish; Ay, Muhammet; Luo, Jie; Zielonka, Jacek; Brenza, Timothy; Bennett, Brian; Jin, Huajun; Ghaisas, Shivani; Schlichtmann, Benjamin; Kim, Dongsuk; Anantharam, Vellareddy; Kanthasamy, Arthi; Narasimhan, Balaji; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

2017-11-10

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction. Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation. The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches. Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048-1066.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Improving comparability of international migration statistics: contributions by the Conference of European Statisticians from 1971 to date.

PubMed

Kelly, J J

1987-01-01

This article summarizes the 3 main types of interrelated activities which the Conference of European Statisticians has worked on to improve the measurement and international comparability of international migration flows. The work has encompassed collaborating with the UN Statistical Commission on the preparation and implementation of the revised international recommendations on statistics of international migration, organizing a regular exchange of data on immigration and emigration flows among the UN Economic Commission for Europe countries and selected countries in other regions, and conducting bilateral studies on international migration within the framework of the Conference's program of work in this field of statistics. The bulk of the work which has been carried out to date by the conference has been conducted rather anonymously and even unobtrusively by the staff of national statistical offices in Economic Commission for Europe countries; they have achieved a modest but important amount of progress during the past 15 years. There is reason to expect that further progress will be made over the next decade, particularly if national statistical offices in the region continue to undertake bilateral studies and endeavor to improve their migration statistics. However, more substantial progress could be achieved if additional countries and organizations established projects aimed at achieving these ends (author's modified).

Respiratory failure due to tracheobronchomalacia.

PubMed Central

Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.

1996-01-01

A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair. PMID:8711665

JPRS Report, China, Selected Provincial Reports.

DTIC Science & Technology

1991-07-26

114.8 billion yuan. The province’s gross value of the scientific and technological sector, vast numbers of industrial output totalled 219.77 billion...and technological progress made increasingly were valued at 57.04 billion yuan, increasing at an important contributions to economic growth. Educa...outlook and investment environment showed new fairly comfortable life. In 1990, urban people’s per- improvements. The pace of technological transforma

Carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Hobday, Timothy J; Abel, Martin D; Pellikka, Patricia A

2007-01-01

Carcinoid heart disease is a rare form of valvular heart disease. The management of these patients is complex, as the systemic malignant disease and the cardiac involvement have to be considered at the same time. Progress in the treatment of patients with carcinoid disease has resulted in improved symptom control and survival. Development and progression of carcinoid heart disease are associated with increased morbidity and mortality. In patients with severe cardiac involvement and well-controlled systemic disease, cardiac surgery has been recognized as the only effective treatment option. Valve replacement surgery may not only be beneficial in terms of symptom relief, but may also contribute to the improved survival observed over the past 2 decades in patients with carcinoid heart disease. Early diagnosis and early surgical treatment in appropriately selected patients may provide the best results. In this article, we review the current literature regarding the biology, diagnosis, treatment, and prognosis of carcinoid heart disease.

A model to begin to use clinical outcomes in medical education.

PubMed

Haan, Constance K; Edwards, Fred H; Poole, Betty; Godley, Melissa; Genuardi, Frank J; Zenni, Elisa A

2008-06-01

The latest phase of the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project challenges graduate medical education (GME) programs to select meaningful clinical quality indicators by which to measure trainee performance and progress, as well as to assess and improve educational effectiveness of programs. The authors describe efforts to measure educational quality, incorporating measurable patient-care outcomes to guide improvement. University of Florida College of Medicine-Jacksonville education leaders developed a tiered framework for selecting clinical indicators whose outcomes would illustrate integration of the ACGME competencies and their assessment with learning and clinical care. In order of preference, indicators selected should align with a specialty's (1) national benchmarked consensus standards, (2) national specialty society standards, (3) standards of local, institutional, or regional quality initiatives, or (4) top-priority diagnostic and/or therapeutic categories for the specialty, based on areas of high frequency, impact, or cost. All programs successfully applied the tiered process to clinical indicator selection and then identified data sources to track clinical outcomes. Using clinical outcomes in resident evaluation assesses the resident's performance as reflective of his or her participation in the health care delivery team. Programmatic improvements are driven by clinical outcomes that are shown to be below benchmark across the residents. Selecting appropriate clinical indicators-representative of quality of care and of graduate medical education-is the first step toward tracking educational outcomes using clinical data as the basis for evaluation and improvement. This effort is an important aspect of orienting trainees to using data for monitoring and improving care processes and outcomes throughout their careers.

Distal muscle involvement in granulomatous myositis can mimic inclusion body myositis.

PubMed

Larue, Sandrine; Maisonobe, Thierry; Benveniste, Olivier; Chapelon-Abric, Catherine; Lidove, Olivier; Papo, Thomas; Eymard, Bruno; Dubourg, Odile

2011-06-01

The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.

Cross-Sectional Data That Explore the Relationship Between Outpatients' Quality of Life and Preferences for Quality Improvement in Oncology Settings.

PubMed

Fradgley, Elizabeth A; Bryant, Jamie; Paul, Christine L; Hall, Alix E; Sanson-Fisher, Robert W; Oldmeadow, Christopher

2016-06-01

This cross-sectional study assessed the association between oncology outpatients' quality improvement preferences and health-related quality of life (HRQoL). Implementation of specific initiatives preferred by patients with lower HRQoL may be a strategic approach to enhancing care for potentially vulnerable patients. English-speaking adults were recruited from five outpatient chemotherapy clinics located in New South Wales, Australia. Using touch screen devices, participants selected up to 25 initiatives that would improve their experiences and completed the Functional Assessment of Cancer Therapy-General (FACT-G) survey. The logistic odds of selecting an initiative according to FACT-G scores were calculated to determine whether preferences were associated with HRQoL after controlling for potential confounders. Of the 411 eligible outpatients approached to participate, 263 (64%) completed surveys. Commonly selected initiatives were up-to-date information on treatment and condition progress (19.8%), access to or information on financial assistance (18.3%), and reduced clinic wait times (17.5%). For those with relatively lower FACT-G scores, the adjusted odds of selecting five initiatives illustrated an increasing trend: convenient appointment scheduling systems (+23% [P = .002]), reduced wait times (+15% [P = .01]), information on medical emergencies (+14% [P = .04]), access to or information on financial assistance (+15% [P = .009]), help to maintain daily living activities (+18% [P = .007]). Two areas of improvement were commonly selected: easily accessible health services and information and support for self-management. Although the results suggest an association between a few quality improvement preferences and HRQoL, a wider spectrum of patient characteristics must be considered when targeting quality improvement to patient subgroups. Copyright © 2016 by American Society of Clinical Oncology.

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis.

PubMed

Gertz, Morie A; Lacy, Martha Q; Dispenzieri, Angela; Buadi, Francis K; Dingli, David; Hayman, Suzanne R; Kumar, Shaji K; Leung, Nelson; Lust, John; Rajkumar, S Vincent; Russell, Stephen J; Suman, Vera J; Le-Rademacher, Jennifer G; Hogan, William J

2016-07-15

Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival. Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis. Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01). Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. © 2016 American Cancer Society.

Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

PubMed

Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

2016-02-17

Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A.

Factors Contributing to Maternal and Child Mortality Reductions in 146 Low- and Middle-Income Countries between 1990 and 2010.

PubMed

Bishai, David M; Cohen, Robert; Alfonso, Y Natalia; Adam, Taghreed; Kuruvilla, Shyama; Schweitzer, Julian

2016-01-01

From 1990-2010, worldwide child mortality declined by 43%, and maternal mortality declined by 40%. This paper compares two sources of progress: improvements in societal coverage of health determinants versus improvements in the impact of health determinants as a result of technical change. This paper decomposes the progress made by 146 low- and middle-income countries (LMICs) in lowering childhood and maternal mortality into one component due to better health determinants like literacy, income, and health coverage and a second component due to changes in the impact of these health determinants. Health determinants were selected from eight distinct health-impacting sectors. Health determinants were selected from eight distinct health-impacting sectors. Regression models are used to estimate impact size in 1990 and again in 2010. Changes in the levels of health determinants were measured using secondary data. The model shows that respectively 100% and 89% of the reductions in maternal and child mortality since 1990 were due to improvements in nationwide coverage of health determinants. The relative share of overall improvement attributable to any single determinant varies by country and by model specification. However, in aggregate, approximately 50% of the mortality reductions were due to improvements in the health sector, and the other 50% of the mortality reductions were due to gains outside the health sector. Overall, countries improved maternal and child health (MCH) from 1990 to 2010 mainly through improvements in the societal coverage of a broad array of health system, social, economic and environmental determinants of child health. These findings vindicate efforts by the global community to obtain such improvements, and align with the post-2015 development agenda that builds on the lessons from the MDGs and highlights the importance of promoting health and sustainable development in a more integrated manner across sectors.

Genetic control of complex traits, with a focus on reproduction in pigs.

PubMed

Zak, Louisa J; Gaustad, Ann Helen; Bolarin, Alfonso; Broekhuijse, Marleen L W J; Walling, Grant A; Knol, Egbert F

2017-09-01

Reproductive traits are complex, and desirable reproductive phenotypes, such as litter size or semen quality, are true polygenetic traits determined by multiple gene regulatory pathways. Each individual gene contributes to the overall variation in these traits, so genetic improvements can be achieved using conventional selection methodology. In the past, a pedigree-based-relationship matrix was used; this is now replaced by a combination of pedigree-based- and genomic-relationship matrices. The heritability of reproductive traits is low to moderate, so large-scale data recording is required to identify specific, selectable attributes. Male reproductive traits-including ejaculate volume and sperm progressive motility-are moderately heritable, and could be used in selection programs. A few high-merit artificial-insemination boars can impact many sow populations, so additional knowledge about male reproduction-specifically pre-pubertal detection of infertility and the technologies of semen cryopreservation and sex sorting-should further improve global breeding efforts. Conversely, female pig reproduction is currently a limiting factor of genetic improvement. Litter size and farrowing interval are the main obstacles to increasing selection intensity and to reducing generation interval in a breeding program. Age at puberty and weaning-to-estrus interval can be selected for, thereby reducing the number of non-productive days. The number of piglets born alive and litter weights are also reliably influenced by genetic selection. Characterization of genotype-environment interactions will provide opportunities to match genetics to specific farm systems. Continued investment to understand physiological models for improved phenotyping and the development of technologies to facilitate pig embryo production for genetic selection are warranted to ensure optimal breeding in future generations. © 2017 Wiley Periodicals, Inc.

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

The mechanism of action of radiosensitization of conventional chemotherapeutic agents.

PubMed

Lawrence, Theodore S; Blackstock, A William; McGinn, Cornelius

2003-01-01

It is not an exaggeration to state that most of the advances in curing cancer in the last decade have come from successful combinations of conventional chemotherapeutic agents with radiation therapy. Further improvements in therapy will depend on understanding the mechanisms by which chemotherapy improves the effectiveness of radiation in model systems and in patients. In this review, we discuss the mechanisms of action of the fluoropyrimidines, gemcitabine, and the platinums. The fluoropyrimidines (5-fluorouracil and fluorodeoxyuridine) increase the effectiveness of radiation chiefly when given before and during radiation. Increased radiation sensitivity occurs in cells that progress inappropriately into S phase in the presence of drug, suggesting a key role for dysregulation of S-phase checkpoints. Gemcitabine may radiosensitize by a similar mechanism, although the relative roles of specific DNA repair pathways (such as homologous end rejoining) and of apoptosis remain to be determined. For both of these categories of drugs, sensitization probably results when cells that are progressing inappropriately through S phase misrepair DNA damage inflicted by radiation. Thus, loss of the S-phase checkpoint in cancer cells may provide the molecular basis for selective killing of tumors compared with normal tissues. Cisplatin has multiple effects on cells, such as adduct formation and DNA damage repair inhibition, but the mechanism for selectivity against cancer cells compared with normal cells is not yet determined. The identification of the enzymatic targets for these drugs offers the potential to develop predictive assays for response and to develop methods of imaging the progress of therapy. Copyright 2003, Elsevier Science (USA). All rights reserved.

Continuous selection pressure to improve temperature acclimation of Tisochrysis lutea

PubMed Central

Grimaud, Ghjuvan; Rumin, Judith; Bougaran, Gaël; Talec, Amélie; Gachelin, Manon; Boutoute, Marc; Pruvost, Eric; Bernard, Olivier; Sciandra, Antoine

2017-01-01

Temperature plays a key role in outdoor industrial cultivation of microalgae. Improving the thermal tolerance of microalgae to both daily and seasonal temperature fluctuations can thus contribute to increase their annual productivity. A long term selection experiment was carried out to increase the thermal niche (temperature range for which the growth is possible) of a neutral lipid overproducing strain of Tisochrysis lutea. The experimental protocol consisted to submit cells to daily variations of temperature for 7 months. The stress intensity, defined as the amplitude of daily temperature variations, was progressively increased along successive selection cycles. Only the amplitude of the temperature variations were increased, the daily average temperature was kept constant along the experiment. This protocol resulted in a thermal niche increase by 3°C (+16.5%), with an enhancement by 9% of the maximal growth rate. The selection process also affected T. lutea physiology, with a feature generally observed for ‘cold-temperature’ type of adaptation. The amount of total and neutral lipids was significantly increased, and eventually productivity was increased by 34%. This seven month selection experiment, carried out in a highly dynamic environment, challenges some of the hypotheses classically advanced to explain the temperature response of microalgae. PMID:28902878

Spectrally queued feature selection for robotic visual odometery

NASA Astrophysics Data System (ADS)

Pirozzo, David M.; Frederick, Philip A.; Hunt, Shawn; Theisen, Bernard; Del Rose, Mike

2011-01-01

Over the last two decades, research in Unmanned Vehicles (UV) has rapidly progressed and become more influenced by the field of biological sciences. Researchers have been investigating mechanical aspects of varying species to improve UV air and ground intrinsic mobility, they have been exploring the computational aspects of the brain for the development of pattern recognition and decision algorithms and they have been exploring perception capabilities of numerous animals and insects. This paper describes a 3 month exploratory applied research effort performed at the US ARMY Research, Development and Engineering Command's (RDECOM) Tank Automotive Research, Development and Engineering Center (TARDEC) in the area of biologically inspired spectrally augmented feature selection for robotic visual odometry. The motivation for this applied research was to develop a feasibility analysis on multi-spectrally queued feature selection, with improved temporal stability, for the purposes of visual odometry. The intended application is future semi-autonomous Unmanned Ground Vehicle (UGV) control as the richness of data sets required to enable human like behavior in these systems has yet to be defined.

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

PubMed Central

Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

2016-01-01

Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

From mission to measures: performance measure development for a Teen Pregnancy Prevention Program.

PubMed

Farb, Amy Feldman; Burrus, Barri; Wallace, Ina F; Wilson, Ellen K; Peele, John E

2014-03-01

The Office of Adolescent Health (OAH) sought to create a comprehensive set of performance measures to capture the performance of the Teen Pregnancy Prevention (TPP) program. This performance measurement system needed to provide measures that could be used internally (by both OAH and the TPP grantees) for management and program improvement as well as externally to communicate the program's progress to other interested stakeholders and Congress. This article describes the selected measures and outlines the considerations behind the TPP measurement development process. Issues faced, challenges encountered, and lessons learned have broad applicability for other federal agencies and, specifically, for TPP programs interested in assessing their own performance and progress. Published by Elsevier Inc.

Comparative Effects of Different Balance-Training-Progression Styles on Postural Control and Ankle Force Production: A Randomized Controlled Trial.

PubMed

Cuğ, Mutlu; Duncan, Ashley; Wikstrom, Erik

2016-02-01

Despite the effectiveness of balance training, the exact parameters needed to maximize the benefits of such programs remain unknown. One such factor is how individuals should progress to higher levels of task difficulty within a balance-training program. Yet no investigators have directly compared different balance-training-progression styles. To compare an error-based progression (ie, advance when proficient at a task) with a repetition-based progression (ie, advance after a set amount of repetitions) style during a balance-training program in healthy individuals. Randomized controlled trial. Research laboratory. A total of 28 (16 women, 12 men) physically healthy young adults (age = 21.57 ± 3.95 years, height = 171.60 ± 11.03 cm, weight = 72.96 ± 16.18 kg, body mass index = 24.53 ± 3.7). All participants completed 12 supervised balance-training sessions over 4 weeks. Each session consisted of a combination of dynamic unstable-surface tasks that incorporated a BOSU ball and lasted about 30 minutes. Static balance from an instrumented force plate, dynamic balance as measured via the Star Excursion Balance Test, and ankle force production in all 4 cardinal planes of motion as measured with a handheld dynamometer before and after the intervention. Selected static postural-control outcomes, dynamic postural control, and ankle force production in all planes of motion improved (P < .05). However, no differences between the progression styles were observed (P > .05) for any of the outcome measures. A 4-week balance-training program consisting of dynamic unstable-surface exercises on a BOSU ball improved dynamic postural control and ankle force production in healthy young adults. These results suggest that an error-based balance-training program is comparable with but not superior to a repetition-based balance-training program in improving postural control and ankle force production in healthy young adults.

Treating cancer with selective CDK4/6 inhibitors.

PubMed

O'Leary, Ben; Finn, Richard S; Turner, Nicholas C

2016-07-01

Uncontrolled cellular proliferation, mediated by dysregulation of the cell-cycle machinery and activation of cyclin-dependent kinases (CDKs) to promote cell-cycle progression, lies at the heart of cancer as a pathological process. Clinical implementation of first-generation, nonselective CDK inhibitors, designed to inhibit this proliferation, was originally hampered by the high risk of toxicity and lack of efficacy noted with these agents. The emergence of a new generation of selective CDK4/6 inhibitors, including ribociclib, abemaciclib and palbociclib, has enabled tumour types in which CDK4/6 has a pivotal role in the G1-to-S-phase cell-cycle transition to be targeted with improved effectiveness, and fewer adverse effects. Results of pivotal phase III trials investigating palbociclib in patients with advanced-stage oestrogen receptor (ER)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a well-tolerated toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge that, although unwelcome, might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response, and the use of combination therapies in order to optimize CDK4/6 targeting.

Improving the availability and accessibility of opioids for the treatment of pain: the International Pain Policy Fellowship.

PubMed

Bosnjak, Snezana; Maurer, Martha A; Ryan, Karen M; Leon, Marta X; Madiye, Gabriel

2011-08-01

Opioid analgesics are simultaneously indispensable medicines for the treatment of moderate to severe pain and are harmful when abused. The challenge for governments is to balance the obligation to prevent diversion, trafficking, and abuse of opioids with the equally important obligation to ensure their availability and accessibility for the relief of pain and suffering. Over the last 30 years, significant progress has been made toward improving access to opioids as measured by increasing global medical opioid consumption. However, this progress is marked by ongoing large disparities among countries, with most increases in medical opioid consumption attributed to high-income countries, not low- and middle-income countries (LMICs). The International Pain Policy Fellowship (IPPF) was developed by the Pain & Policy Studies Group, with the central goal of developing national leaders from LMICs and empowering them to improve availability and accessibility of opioids for the treatment of pain. To date, two classes of fellows have been selected, representing 17 fellows from 15 countries. Progress achieved by the leadership of three fellows from Sierra Leone, Colombia, and Serbia is highlighted in this paper. The fellows from each country were successful at initiating collaboration with relevant governmental bodies, national authorities, and professional societies, which resulted in a new supply of oral opioids in Sierra Leone and Serbia, and improvements in the distribution of already available opioids in Colombia. All fellows were instrumental in facilitating evaluation of national policy. The IPPF program empowers fellows with the necessary knowledge, skills, and guidance to improve the availability and accessibility of opioids for the treatment of pain.

Exploring Deep Learning and Sparse Matrix Format Selection

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

Zhao, Y.; Liao, C.; Shen, X.

We proposed to explore the use of Deep Neural Networks (DNN) for addressing the longstanding barriers. The recent rapid progress of DNN technology has created a large impact in many fields, which has significantly improved the prediction accuracy over traditional machine learning techniques in image classifications, speech recognitions, machine translations, and so on. To some degree, these tasks resemble the decision makings in many HPC tasks, including the aforementioned format selection for SpMV and linear solver selection. For instance, sparse matrix format selection is akin to image classification—such as, to tell whether an image contains a dog or a cat;more » in both problems, the right decisions are primarily determined by the spatial patterns of the elements in an input. For image classification, the patterns are of pixels, and for sparse matrix format selection, they are of non-zero elements. DNN could be naturally applied if we regard a sparse matrix as an image and the format selection or solver selection as classification problems.« less

Computerized progressive attentional training (CPAT) program: effective direct intervention for children with ADHD.

PubMed

Shalev, Lilach; Tsal, Yehoshua; Mevorach, Carmel

2007-07-01

We tested the efficacy of a pioneering intervention program grounded in a contemporary theoretical framework of attention and designed to directly improve the various attentional functions of children with ADHD. The computerized progressive attentional training (CPAT) program is composed of four sets of structured tasks that uniquely activate sustained attention, selective attention, orienting of attention, and executive attention. Performance was driven by tight schedules of feedback and participants automatically advanced in ordered levels of difficulty contingent upon performance. Twenty 6- to 13-year-old children with ADHD were assigned to the experimental group and received the CPAT sessions twice a week over an 8-week period. Sixteen age-matched control children with ADHD were assigned to the control group and participated in sessions of the same frequency, length, and format except that instead of performing the training tasks they played various computer games during the session. The experimental participants showed a significant improvement in nontrained measures of reading comprehension, and passage copying as well as a significant reduction of parents' reports of inattentiveness. No significant improvements were observed in the control group. We thus concluded that the above academic and attentional improvements were primarily due to the CPAT.

Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.

PubMed

Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang

2018-02-07

Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

NRC assessment of improvements in licensee procurement and dedication programs

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

Grimes, B.K.; Potapovs, U.; Campbell, L.L.

1991-01-01

The US Nuclear Regulatory Commission (NRC) recently conducted a series of on-site assessments at selected nuclear plants to review improvements that the licenses had made to their procurement and dedication activities. The assessments included an evaluation of the progress made by licensees to strengthen their commercial-grade dedication programs to comply with 10CRF50, Appendix B, and to implement the comprehensive procurement improvements suggested in Nuclear Management and Resource Council (NUMARC) publication 901-3. This paper discusses the overall purpose of the assessments, procurement areas assessed, major strengths and weaknesses identified in licensee procurement programs, and the NRC's perspective of the industry's responsemore » to NUMARC procurement initiatives.« less

Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement

PubMed Central

Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

2011-01-01

I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and FG-MD, were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of beta-proteins are still needed to further improve the I-TASSER pipeline. PMID:22069036

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Tackling Health Inequalities in the United Kingdom: The Progress and Pitfalls of Policy

PubMed Central

Exworthy, Mark; Blane, David; Marmot, Michael

2003-01-01

Goal Assess the progress and pitfalls of current United Kingdom (U.K.) policies to reduce health inequalities. Objectives (1) Describe the context enabling health inequalities to get onto the policy agenda in the United Kingdom. (2) Categorize and assess selected current U.K. policies that may affect health inequalities. (3) Apply the “policy windows” model to understand the issues faced in formulating and implementing such policies. (4) Examine the emerging policy challenges in the U.K. and elsewhere. Data Sources Official documents, secondary analyses, and interviews with policymakers. Study Design Qualitative, policy analysis. Data Collection 2001–2002. The methods were divided into two stages. The first identified policies which were connected with individual inquiry recommendations. The second involved case-studies of three policies areas which were thought to be crucial in tackling health inequalities. Both stages involved interviews with policy-makers and documentary analysis. Principal Findings (1) The current U.K. government stated a commitment to reducing health inequalities. (2) The government has begun to implement policies that address the wider determinants. (3) Some progress is evident but many indicators remain stubborn. (4) Difficulties remain in terms of coordinating policies across government and measuring progress. (5) The “policy windows” model explains the limited extent of progress and highlights current and possible future pitfalls. (6) The U.K.'s experience has lessons for other governments involved in tackling health inequalities. Conclusions Health inequalities are on the agenda of U.K. government policy and steps have been made to address them. There are some signs of progress but much remains to be done including overcoming some of the perverse incentives at the national level, improving joint working, ensuring appropriate measures of performance/progress, and improving monitoring arrangements. A conceptual policy model aids understanding and points to ways of sustaining and extending the recent progress and overcoming pitfalls. PMID:14727803

Progress in revising and supplementing fundamental optical ISO standards

NASA Astrophysics Data System (ADS)

Schuhmann, Rainer

2017-11-01

This overview reflects the ISO working group activities of ISO/TC 172 Subcommittee 1 during the last years which have resulted in revisions and new ISO standards for optical components. For ISO 10110, ISO 14999 and other standards new surface forms and metrology techniques have been considered, standards about material characteristics have been consolidated, and optical drawings have been updated. Selected examples of new improvements and future work items are given.

Progress towards the Millennium Development Goals in a community of extreme poverty: local vs. national disparities in Peru.

PubMed

Gyorkos, Theresa W; Joseph, Serene A; Casapía, Martin

2009-06-01

Standard indicators are being used worldwide to track progress towards achieving the Millennium Development Goals (MDGs). These are usually at country level and do not accurately reflect within-country variability of progress towards the targets. This may lead to lack of attention and under-resourcing of the most vulnerable populations. Therefore, the objective of this study was to compare selected standard MDG indicators at country level and community level in Peru. As MDG indicators we selected: (i) moderate to severe and severe underweight in children under 5 years old; (ii) immunization against measles in 1-year olds; (iii) births attended by skilled health professionals and (iv) youth unemployment. Country-level data for Peru were obtained from United Nations published sources. Community-level data were obtained from a household survey conducted in 2005-2006 in Belén, a community of extreme poverty in the Amazon region. Belén indicators were consistently less favourable than country-level indicators, and indicators even differed between zones of high and low socioeconomic status within Belén itself. Compared to MDG indicators at the national level in Peru, the population of Belén experiences intra-country regional disparities in important health and social outcomes. Improving the coverage and quality of interventions and services in this community is essential. Other vulnerable populations in Peru should also be identified and targeted so that they can benefit from, and ultimately contribute to, progress in achieving the MDGs.

Genetic selection for lifetime reproductive performance.

PubMed

Clutter, A C

2009-01-01

Genetic improvement of sow lifetime reproductive performance has value from both the economic perspectives of pork producers and the pork industry, but also from the perspective of ethical and animal welfare concerns by the general public. Genetic potential for piglets produced from individual litters is a primary determinant of lifetime prolificacy, but females must be able to sustain productivity without injury or death beyond the achievement of positive net present value. Evidence exists for between- and within-line genetic variation in sow lifetime performance, suggesting that improvements may be made by both line choices and genetic selection within lines. However, some of the same barriers to accurate within-line selection that apply to individual litter traits also present challenges to genetic selection for sow lifetime prolificacy: generally low heritabilites, sex-limited expression, expression after the age that animals are typically selected, and unfavorable genetic correlations with other traits in the profit function. In addition, there is an inherent conflict within the genetic nucleus herds where selections take place between the goal of shortened generation interval to accelerate genetic progress and the expression of sow lifetime traits. A proliferation in the industry of commercial multipliers with direct genetic ties and routine record flows to genetic nucleus herds provides a framework for accurate estimates of relevant genetic variances and covariances, and estimation of breeding values for sow lifetime traits that can be used in genetic selection.

Selecting interventions to promote fruit and vegetable consumption: from policy to action, a planning framework case study in Western Australia.

PubMed

Pollard, Christina M; Lewis, Janette M; Binns, Colin W

2008-12-24

The Department of Health in Western Australia identified access to, and daily consumption of recommended amounts of fruit and vegetables, as priority health determinants. The numerous factors that influence supply and consumption of fruit and vegetables indicated that a comprehensive approach would be required.A government and non-government sector steering group was set up to select priority interventions using the National Public Health Partnership's Framework for Implementing Public Health Strategies. This structured framework was used for developing strategies to improve fruit and vegetable consumption and supply, and to identify implementation priorities.After one year a desktop audit of progress on framework interventions was undertaken. The structured framework led to a plan for defined actions, partners, costs, and performance indicators for strategies to improve fruit and vegetable consumption and supply. Lead agency custodians for management of the selected interventions were identified.After one year there was significant progress in the implementation of a number of the high-ranking interventions. The exception was interventions that provide the infrastructure support such as research and development capacity, information systems. A structured framework and stakeholder participation assisted in developing a fruit and vegetable implementation strategy. Engagement and commitment of influential and diverse stakeholders is needed, not just for program support, but particularly in the areas of food and nutrition policy development and providing the infrastructure support required. Further work is required to develop performance outcomes and cost effectiveness measures for many of the strategies that have been proposed to address portfolio objectives.

Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy.

PubMed

Cohen, Itay; Kayode, Olumide; Hockla, Alexandra; Sankaran, Banumathi; Radisky, Derek C; Radisky, Evette S; Papo, Niv

2016-05-15

Engineered protein therapeutics offer advantages, including strong target affinity, selectivity and low toxicity, but like natural proteins can be susceptible to proteolytic degradation, thereby limiting their effectiveness. A compelling therapeutic target is mesotrypsin, a protease up-regulated with tumour progression, associated with poor prognosis, and implicated in tumour growth and progression of many cancers. However, with its unique capability for cleavage and inactivation of proteinaceous inhibitors, mesotrypsin presents a formidable challenge to the development of biological inhibitors. We used a powerful yeast display platform for directed evolution, employing a novel multi-modal library screening strategy, to engineer the human amyloid precursor protein Kunitz protease inhibitor domain (APPI) simultaneously for increased proteolytic stability, stronger binding affinity and improved selectivity for mesotrypsin inhibition. We identified a triple mutant APPIM17G/I18F/F34V, with a mesotrypsin inhibition constant (Ki) of 89 pM, as the strongest mesotrypsin inhibitor yet reported; this variant displays 1459-fold improved affinity, up to 350 000-fold greater specificity and 83-fold improved proteolytic stability compared with wild-type APPI. We demonstrated that APPIM17G/I18F/F34V acts as a functional inhibitor in cell-based models of mesotrypsin-dependent prostate cancer cellular invasiveness. Additionally, by solving the crystal structure of the APPIM17G/I18F/F34V-mesotrypsin complex, we obtained new insights into the structural and mechanistic basis for improved binding and proteolytic resistance. Our study identifies a promising mesotrypsin inhibitor as a starting point for development of anticancer protein therapeutics and establishes proof-of-principle for a novel library screening approach that will be widely applicable for simultaneously evolving proteolytic stability in tandem with desired functionality for diverse protein scaffolds. © 2016 Authors; published by Portland Press Limited.

Progress of liver resection for hepatocellular carcinoma in Taiwan.

PubMed

Wu, Cheng-Chung

2017-05-01

Taiwan is a well-known endemic area of hepatitis B. Hepatocellular carcinoma (HCC) has consistently been the first or second highest cause of cancer death over the past 20 years. This review article describes the progress of liver resection for HCC in Taiwan in the past half century. The mortality rate for HCC resection was 15-30% in Taiwan in the 1970s. The rate decreased to 8-12% in the early 1990s, and it declined to <1-3% recently. The development of new operative instruments, and surgical techniques, increased knowledge of liver anatomy and pathophysiology after hepatectomy, and more precise patient selection have contributed to this improvement. The use of intermittent hepatic inflow blood occlusion, a restrictive blood transfusion policy and intraoperative ultrasonography, have also led to substantial improvements in resectability and safety for HCC resection in Taiwan. Advances in non-operative modalities for HCC treatment have also helped to improve long-term outcomes of HCC resection. Technical innovations have allowed the application of complex procedures such as mesohepatectomy, unroofing hepatectomy, major portal vein thrombectomy, hepatic vein reconstruction in resection of the cranial part with preservation of the caudal part of the liver, and inferior vena cava and right atrium tumor thrombectomy under cardiopulmonary bypass. In selected patients, including patients with end-stage renal failure, renal graft recipients, patients with portal hypertension, hypersplenic thrombocytopenia and/or associated gastroesophageal varices, octogenarian, ruptured HCC, recurrent HCC and metastatic HCC can also be resected with satisfactory survival benefits. We conclude that the results of liver resection for HCC in Taiwan are improving. The indications for HCC resection continue extending with lower the surgical risks and increasing the long-term survival rate. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Circulating Tumor Cell Increase as a Biomarker of Disease Progression in Metastatic Castration-Resistant Prostate Cancer Patients with Low Baseline CTC Counts.

PubMed

Lorente, D; Olmos, D; Mateo, J; Dolling, D; Bianchini, D; Seed, G; Flohr, P; Crespo, M; Figueiredo, I; Miranda, S; Scher, H I; Terstappen, L W M M; de Bono, J S

2018-05-07

The development of treatment response and surrogate biomarkers for advanced prostate cancer care is an unmet clinical need. Patients with baseline circulating tumor cell counts (BLCTCs)<5/7.5 mL represent a good prognosis subgroup, but are non-evaluable for response assessment (decrease in CTCs). The aim of the study is to determine the value of any increase in CTCs (CTC Progression) as an indicator of progression in prostate cancer patients with low pre-treatment CTCs (<5). We performed a post-hoc analysis of patients with BLCTCs < 5 treated in the COU-AA-301 (abiraterone or placebo + prednisone) and IMMC-38 (chemotherapy) trials. The association of CTC Progression (increase in CTCs at 4, 8 or 12 weeks) with overall survival (OS) was evaluated in multivariable Cox regression models. Performance of survival models with and without CTC Progression was evaluated by calculating ROC curve AUCs and weighted c-indices. Overall, 511 patients with CTCs <5 (421 in COU-AA-301; 90 in IMMC-38) were selected; 212 (41.7%) had CTC Progression at 4, 8 or 12 weeks after treatment initiation. CTC Progression was associated with significantly worse OS (27.1 vs 15.1m; HR: 3.4 [95%CI:2.5-4.5; p < 0.001]); independent of baseline CTCs and established clinical variables. Adding CTC Progression to the OS model significantly improved ROC AUC (0.77 vs 0.66; p < 0.001). Models including CTC Progression had superior ROC AUC (0.77 vs 0.69; p < 0.001) and weighted c-index (0.750 vs 0.705; delta c-index: 0.045 [95%CI: 0.019-0.071]) values than those including CTC conversion (increase to CTCs ≥5). In COU-AA-301, the impact of CTC Progression was independent of treatment arm. Increasing CTCs during the first 12-weeks of treatment are independently associated with worse OS from advanced prostate cancer in patients with baseline CTCs < 5 treated with abiraterone or chemotherapy and improve models with established prognostic variables. These findings must be prospectively validated.

Impact of disease heterogeneity on treatment efficacy of immunotherapy in Type 1 diabetes: different shades of gray.

PubMed

Woittiez, Nicky J C; Roep, Bart O

2015-01-01

Type 1 diabetes results from selective destruction of insulin-producing pancreatic β-cells by a progressive autoimmune process. Type 1 diabetes proves very heterogeneous in pathology, disease progression and efficacy of therapeutic intervention. Indeed, several immunotherapies that appear ineffective for the entire treated patient population in fact look promising in subgroups of patients. It therefore seems inconceivable that one standard therapy will provide the golden bullet of disease intervention. Instead, personalized medicine may improve immune intervention efficacy rates. We discuss the effect of disease heterogeneity on treatment outcome of immunotherapies, identifying apparent gaps in our understanding of treatment efficacy in subgroups of Type 1 diabetic patients as well as identifying future opportunities for immunotherapy.

Challenges for allergy diagnosis in regions with complex pollen exposures.

PubMed

Barber, Domingo; Díaz-Perales, Araceli; Villalba, Mayte; Chivato, Tomas

2015-02-01

Over the past few decades, significant scientific progress has influenced clinical allergy practice. The biological standardization of extracts was followed by the massive identification and characterization of new allergens and their progressive use as diagnostic tools including allergen micro arrays that facilitate the simultaneous testing of more than 100 allergen components. Specific diagnosis is the basis of allergy practice and is always aiming to select the best therapeutic or avoidance intervention. As a consequence, redundant or irrelevant information might be adding unnecessary cost and complexity to daily clinical practice. A rational use of the different diagnostic alternatives would allow a significant improvement in the diagnosis and treatment of allergic patients, especially for those residing in complex pollen exposure areas.

[Current status and perspectives of diagnosis and treatment of complications related to liver cirrhosis].

PubMed

Nan, Y M

2017-04-20

Liver cirrhosis is the severe period of chronic liver diseases, especially decompensated liver cirrhosis and its complications, such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury, and hepatocellular carcinoma, which greatly affect patients' quality of life and even threaten their lives. Early prevention and treatment of the causes of development and progression and pathogenic mechanism may slow down or reverse liver cirrhosis and its severe complications. Once the disease progresses to portal hypertension and related complications, it is very important to select preventive measures for acute exacerbation of different complications, as well as the methods and timing for treatment in acute stage, which may help to save patients' lives and improve their prognosis.

Changes in the structures of motile sperm subpopulations in dog spermatozoa after both cryopreservation and centrifugation on PureSperm(®) gradient.

PubMed

Dorado, J; Alcaráz, L; Duarte, N; Portero, J M; Acha, D; Hidalgo, M

2011-05-01

The aims of the present study were to: (1) determine if discrete motile sperm subpopulations exist and their incidence in fresh dog ejaculates, (2) evaluate the effects of cryopreservation on the distribution of spermatozoa within the different subpopulations, and (3) determine the effect of the discontinuous PureSperm(®) gradient on the sperm subpopulation structure of frozen-thawed dog spermatozoa. Semen from 5 dogs were collected and cryopreserved following a standard protocol. After thawing, semen samples were selected by centrifugation on PureSperm(®). Sperm motility (assessed by computerized-assisted semen analysis, CASA) was assessed before freezing, just after thawing and after preparation on the PureSperm(®) gradients. Cryopreservation had a significant (P<0.001) effect on CASA-derived parameters. PureSperm(®) centrifugation yielded sperm suspensions with improved motility (P<0.01). A multivariate clustering procedure separated 19414 motile spermatozoa into four subpopulations: Subpopulation 1 consisting of poorly active and non-progressive spermatozoa (20.97%), Subpopulation 2 consisting of slow and low-linear spermatozoa (18.24%), Subpopulation 3 consisting of highly active but non-progressive spermatozoa (20.75%), and Subpopulation 4 consisting of high speed and progressive spermatozoa (40.03%). Although, cryopreservation had a significant (P<0.001) effect on both the frequency distribution of spermatozoa within subpopulations and the motion characteristics of each subpopulation, the sperm subpopulation structure was perfectly maintained after freezing and thawing. The selected sperm samples was enrich in Subpopulation 4, reaching a proportion of 31.9% of the present spermatozoa, in contrast with the unselected sperm samples, where this sperm subpopulation accounted for 24.9% of the total. From these results, we concluded that four well-defined motile sperm subpopulations were present either in fresh semen, in unselected sperm samples or in selected preparations from dogs. The discontinuous PureSperm(®) gradient is a simple method to improve the quality of canine frozen-thawed semen samples, since Subpopulation 4 (high-speed and progressive spermatozoa) was more frequently observed after preparation on the gradient. Finally, this study also demonstrated that the general motile sperm structure present in dog remains constant despite the effect caused by either cryopreservation or separation on PureSperm(®) gradient. Copyright © 2011 Elsevier B.V. All rights reserved.

Selective breeding in fish and conservation of genetic resources for aquaculture.

PubMed

Lind, C E; Ponzoni, R W; Nguyen, N H; Khaw, H L

2012-08-01

To satisfy increasing demands for fish as food, progress must occur towards greater aquaculture productivity whilst retaining the wild and farmed genetic resources that underpin global fish production. We review the main selection methods that have been developed for genetic improvement in aquaculture, and discuss their virtues and shortcomings. Examples of the application of mass, cohort, within family, and combined between-family and within-family selection are given. In addition, we review the manner in which fish genetic resources can be lost at the intra-specific, species and ecosystem levels and discuss options to best prevent this. We illustrate that fundamental principles of genetic management are common in the implementation of both selective breeding and conservation programmes, and should be emphasized in capacity development efforts. We highlight the value of applied genetics approaches for increasing aquaculture productivity and the conservation of fish genetic resources. © 2012 Blackwell Verlag GmbH.

Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

PubMed

Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

2013-02-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

PubMed Central

Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

2013-01-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

Management of mantle cell lymphoma in the elderly patient

PubMed Central

Doorduijn, Jeanette K; Kluin-Nelemans, Hanneke C

2013-01-01

Mantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of patients, especially the elderly, the aim of therapy should therefore be a long progression-free survival. Age and comorbidity may hamper the use of the most active treatment regimen, such as high dose cytarabine and autologous stem cell transplantation. Therefore, it is a challenge to select the most appropriate therapy for an elderly patient. Studies specifically designed for elderly patients are rare. A recently performed large randomized study for elderly patients, however, has shown that R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed by maintenance rituximab can result in a long progression-free survival. For patients too frail for R-CHOP chemotherapy, a treatment should be offered that benefits the patient in reducing the symptoms of the disease without causing too many side effects. Progression or relapse will occur in all patients sooner or later. Second-line treatment should again be carefully selected. Several options are mentioned. New drugs are being developed, and new combinations are investigated. Further improvement in the outcome of patients with mantle cell lymphoma is expected. Participation in well-designed clinical trials, also by elderly patients, is important to find the real benefit that can be achieved, and to get information on the tolerability of these treatments in this age group. PMID:24072968

Improvement of resistance to rust through recurrent selection in pearl millet

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

Tapsoba, H.; Wilson, J.P.; Hanna, W.W.

Two pearl millet [Pennisetum glaucum (L.) R.Br. = P. typhoides (Burm.) Staff & Hubb., P. americanum (L.) K. Schum.] bulk populations, Tift No. 2 and Tift No. 5, served as base populations for four cycles of recurrent selection against susceptibility to Puccinia substriata Ell. & Barth, var. indica Ramachar & Cumm. A bulk inoculum of the pathogen was used. The objectives were to evaluate the progress achieved regarding overall resistance to the pathogen in the field and resistance to different races of the pathogen, and also to evaluate changes in unselected traits. During selection, the frequency of rust resistant plantsmore » continuously increased from about 30% in each base population to more than 85% by the third cycle of selection in both populations. An average increase of about 21 and 18% per cycle was obtained in Tift No. 2 and Tift No. 5, respectively. A continuous increase of the frequency of plants resistant to some races of the pathogen was also obtained. In Tift No. 5, 80% of the plants were resistant to eight races by the third cycle of selection. The accumulation of resistance observed in the seedlings was manifested in the field, both in 1993 and 1994, by a reduction of the final rust severity from the base population to the fourth selection cycle of both populations. This improvement in resistance to the rust pathogen was accompanied by an increase in the frequency of plants resistant to Pyricularia grisea (Cooke) Sacc. only in Tift No. 2. Despite the improvement in the selected character, genetic variability for agronomic traits such as plant height, number of culms/plant, flowering date, and panicle length was successfully maintained within each population. 20 refs., 1 fig., 7 tabs.« less

Recent progress in the biology of multiple myeloma and future directions in the treatment.

PubMed

Pico, J L; Castagna, L; Bourhis, J H

1998-04-01

A great amount of scientific information, accumulated over recent years on the biology of Multiple Myeloma (MM), has fuelled speculation about the origin of malignant plasma cells, about a purported critical role played by the bone marrow stroma, and further still, on cytokine interactions and in particular that of IL-6 and its relationship with the immune system. Among the growth factors secreted by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does not induce a malignant phenotype in normal plasma cells. Many efforts have been produced to identify the stem cell in MM and probably memory B lymphocytes are the best candidates. The demonstration of a Graft vs Myeloma effect in the allogeneic setting strongly supports the immunotherapy in MM. Recent data also suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly associated with the development of MM. In parallel, progress has been achieved in the treatment of this incurable disease with well defined prognostic factors, more efficient supportive care and its corollary, improved quality of life and dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem cell support. Improving the quality of grafts with the selection of CD34 positive cells is another approach aimed at reducing plasma cell contamination without impairing haematological recovery. An EBMT randomized study assessing the role of CD34 selection has been initiated by our group Increasingly efficient first-line therapy, better quality autografts and improved post-remission treatment with, for example, anti-idiopathic vaccination are the most promising future directions.

Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture

PubMed Central

Damato, B

2012-01-01

Uveal melanomas are diverse in their clinical features and behaviour. More than 90% involve the choroid, the remainder being confined to the ciliary body and iris. Most patients experience visual loss and more than a third require enucleation, in some cases because of pain. Diagnosis is based on slit-lamp biomicroscopy and/or ophthalmoscopy, with ultrasonography, autofluorescence photography, and/or biopsy in selected cases. Conservation of the eye with useful vision has improved with advances in brachytherapy, proton beam radiotherapy, endoresection, exoresection, transpupillary thermotherapy, and photodynamic therapy. Despite ocular treatment, almost 50% of patients develop metastatic disease, which occurs almost exclusively in patients whose tumour shows chromosome 3 loss and/or class 2 gene expression profile. When the tumour shows such lethal genetic changes, the survival time depends on the anatomical stage and the histological grade of malignancy. Prognostication has improved as a result of progress in multivariate analysis including all the major risk factors. Screening for metastases is more sensitive as a consequence of advances in liver scanning with magnetic resonance imaging and other methods. More patients with metastases are living longer, benefiting from therapies such as: partial hepatectomy; radiofrequency ablation; ipilumumab immunotherapy; selective internal radiotherapy; intra-hepatic chemotherapy, possibly with isolated liver perfusion; and systemic chemotherapy. There is scope for improvement in the detection of uveal melanoma so as to maximise any opportunities for conserving the eye and vision, as well as preventing metastatic spread. Patient management has been enhanced by the formation of multidisciplinary teams in specialised ocular oncology centres. PMID:22744385

Liver transplantation for hepatocellular carcinoma: a surgical perspective.

PubMed

Fortune, Brett E; Umman, Veysel; Gilliland, Thomas; Emre, Sukru

2013-07-01

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. Early detection and timely treatment of HCC is critical for better patient outcomes. Curative therapy consists of surgical hepatic resection or liver transplantation (LTx); however, both are restricted to explicit selective criteria. Liver resection is the gold standard of treatment for noncirrhotic patients but can be done in only a small fraction of cirrhotic patients depending on synthetic dysfunction, degree of portal hypertension, and number and location(s) of tumor(s). Therefore, the best treatment modality in cirrhotic patients with HCC is LTx as it will cure both HCC and the underlying cirrhosis. The limitation to offer transplant to all cirrhotic patients with HCC is the shortage of available donor organs. While these patients are waiting for transplant, their tumors may progress and develop distant metastases and may lead to patients losing their candidacy for LTx. Various ablation therapies can be used to treat HCC, prevent tumor progression, and thus, avoid patients losing the option of LTx. Future directions to improve HCC patient outcomes include advancement in tumor gene analysis and histopathology for better prediction of tumor behavior, improved immunosuppression regimens to reduce tumor recurrence in the posttransplant setting, and efficient use of an expanded donor pool that includes living donor organs. This paper will review the current methods of HCC diagnosis, selection for either hepatic resection or LTx, and will also summarize posttreatment outcomes. We will suggest future directions for the field as we strive to improve outcomes for our HCC patients.

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to and including the date upon which Phase 2 proposals are requested. Any such changes in evaluation... procurement using a progressive competition down-selection technique between phases. In this technique, two or more contractors will be selected for Phase 1. It is expected that the single contractor for Phase 2...

Hearing on the Reauthorization of the Education of the Deaf Act. Hearing before the Subcommittee on Select Education of the Committee on Education and Labor. House of Representatives, One Hundred Second Congress, Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

This Congressional hearing on the reauthorization of the Education of the Deaf Act examines the progress in implementing research findings and the methods used to provide services to diverse populations within the deaf community. It addresses such issues as the needs of minority deaf students, improving the educational achievement of deaf students…

An audit of inpatient case records and suggestions for improvements.

PubMed

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

2000-09-01

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

The public health effects of water and sanitation in selected West African countries.

PubMed

Alagidede, P; Alagidede, A N

2016-01-01

This paper examines access to water and improved sanitation target under the Millennium Development Goal 7c (MDG 7c) for six West African countries: Chad, Niger, Nigeria, Mauritania, Sierra Leone and Togo. The article outlines some possible causes for the slow progress in achieving the MDG 7c, examines the public health effects of missing the targets, and charts paths for policy makers to consider in bringing these targets to acceptable levels. The study is based on secondary data analysis of trends in water and sanitation indicators for the six countries from 2000 to 2014. The data are drawn from the World Development Indicators (WDI) of the World Bank, and the World Health Organisation Joint Monitoring Programme (WHO JMP) and WaterAid Africa Wash Map. The performance of each country in the two indicators is presented and judged against the target set under MDG 7c. Forecasts based on the expiry of the MDG's in 2015 and the time required to achieve the targets are carried out. The study showes that while some progress has been made in improved water, sanitation showed slow progress for all the countries between 2000 and 2014. The goal of attaining acceptable sanitation shows that the six West African countries have lagged behind the MDG 7c target and the progress is equally slow. At the current rate of progress if strong public and private sector intervention mechanisms are not instituted across the board, the six West African countries under study would continue to lag behind the rest of the world in terms of access to improved water and sanitation. This has consequences for poverty alleviation and the risk of the re-emergence of neglected tropical diseases. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Progress in Rectal Cancer Treatment

PubMed Central

Ceelen, Wim P.

2012-01-01

The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

Yield-trait performance landscapes: from theory to application in breeding maize for drought tolerance.

PubMed

Messina, Carlos D; Podlich, Dean; Dong, Zhanshan; Samples, Mitch; Cooper, Mark

2011-01-01

The effectiveness of breeding strategies to increase drought resistance in crops could be increased further if some of the complexities in gene-to-phenotype (G → P) relations associated with epistasis, pleiotropy, and genotype-by-environment interactions could be captured in realistic G → P models, and represented in a quantitative manner useful for selection. This paper outlines a promising methodology. First, the concept of landscapes was extended from the study of fitness landscapes used in evolutionary genetics to the characterization of yield-trait-performance landscapes for agricultural environments and applications in plant breeding. Second, the E(NK) model of trait genetic architecture was extended to incorporate biophysical, physiological, and statistical components. Third, a graphical representation is proposed to visualize the yield-trait performance landscape concept for use in selection decisions. The methodology was demonstrated at a particular stage of a maize breeding programme with the objective of improving the drought tolerance of maize hybrids for the US Western Corn-Belt. The application of the framework to the genetic improvement of drought tolerance in maize supported selection of Doubled Haploid (DH) lines with improved levels of drought tolerance based on physiological genetic knowledge, prediction of test-cross yield within the target population of environments, and their predicted potential to sustain further genetic progress with additional cycles of selection. The existence of rugged yield-performance landscapes with multiple peaks and intervening valleys of lower performance, as shown in this study, supports the proposition that phenotyping strategies, and the directions emphasized in genomic selection can be improved by creating knowledge of the topology of yield-trait performance landscapes.

Checkpoints to Progression: Qualitative Analysis of the Personal and Contextual Factors That Influence Selection of Upper Extremity Reconstruction Among Patients With Tetraplegia.

PubMed

Harris, Chelsea A; Muller, John-Michael; Shauver, Melissa J; Chung, Kevin C

2017-07-01

Patients with tetraplegia consistently rank better use of the upper extremity as their top functional priority. Multiple case series have demonstrated that upper extremity reconstruction (UER) is well-tolerated and can produce substantial functional improvements for appropriate candidates; however, UER remains critically underutilized. The mechanisms that drive differences in provider practice and referral patterns have been studied, but comprehensive examination of the patient factors that influence UER decisions has not been performed for American patients. Nineteen patients with C4-8 cervical spinal injuries were selected using purposive sampling: 9 patients had undergone UER, 10 had not undergone UER. Semistructured interviews were conducted and transcripts evaluated using grounded theory methodology. Our study yielded a conceptual model that describes the characteristics common to all patients who undergo UER. Patients who selected reconstruction proceeded stepwise through a shared sequence of steps: (1) functional dissatisfaction, (2) awareness of UER, and (3) acceptance of surgery. Patients' ability to meet these criteria was determined by 3 checkpoints: how well they coped, their access to information, and the acceptability of surgery. Extremely positive or negative coping prevented patients from moving from the Coping to the Information Checkpoint; thus, they remained unaware of UER and did not undergo surgery. A lack of knowledge regarding reconstruction was the strongest barrier to surgery among our participants. We built a conceptual model that outlines how patients' personal and contextual factors drive their progression to UER. Moving from functional dissatisfaction to understanding that they were candidates for UER was a substantial barrier for participants, particularly those with very high and very low coping skills. To improve utilization for all patients, interventions are needed to increase UER awareness. Standardizing introduction to UER during the rehabilitation process or improving e-content may represent key awareness access points. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Using Technology Readiness Level (TRL), Life Cycle Cost (LCC), and Other Metrics to Supplement Equivalent System Mass (ESM) in Advanced Life Support (ALS)

NASA Technical Reports Server (NTRS)

Jones, Harry

2003-01-01

The ALS project plan goals are reducing cost, improving performance, and achieving flight readiness. ALS selects projects to advance the mission readiness of low cost, high performance technologies. The role of metrics is to help select good projects and report progress. The Equivalent Mass (EM) of a system is the sum of the estimated mass of the hardware, of its required materials and spares, and of the pressurized volume, power supply, and cooling system needed to support the hardware in space. EM is the total payload launch mass needed to provide and support a system. EM is directly proportional to the launch cost.

Stages in the research process.

PubMed

Gelling, Leslie

2015-03-04

Research should be conducted in a systematic manner, allowing the researcher to progress from a general idea or clinical problem to scientifically rigorous research findings that enable new developments to improve clinical practice. Using a research process helps guide this process. This article is the first in a 26-part series on nursing research. It examines the process that is common to all research, and provides insights into ten different stages of this process: developing the research question, searching and evaluating the literature, selecting the research approach, selecting research methods, gaining access to the research site and data, pilot study, sampling and recruitment, data collection, data analysis, and dissemination of results and implementation of findings.

Improving livestock for agriculture - technological progress from random transgenesis to precision genome editing heralds a new era.

PubMed

Laible, Götz; Wei, Jingwei; Wagner, Stefan

2015-01-01

Humans have a long history in shaping the genetic makeup of livestock to optimize production and meet growing human demands for food and other animal products. Until recently, this has only been possible through traditional breeding and selection, which is a painstakingly slow process of accumulating incremental gains over a long period. The development of transgenic livestock technology offers a more direct approach with the possibility for making genetic improvements with greater impact and within a single generation. However, initially the technology was hampered by technical difficulties and limitations, which have now largely been overcome by progressive improvements over the past 30 years. Particularly, the advent of genome editing in combination with homologous recombination has added a new level of efficiency and precision that holds much promise for the genetic improvement of livestock using the increasing knowledge of the phenotypic impact of genetic sequence variants. So far not a single line of transgenic livestock has gained approval for commercialization. The step change to genome-edited livestock with precise sequence changes may accelerate the path to market, provided applications of this new technology for agriculture can deliver, in addition to economic incentives for producers, also compelling benefits for animals, consumers, and the environment. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress in the molecular and genetic modification breeding of beef cattle in China.

PubMed

Tong, Bin; Zhang, Li; Li, Guang-Peng

2017-11-20

The studies of beef cattle breeding in China have been greatly improved with the rapid development of the international beef cattle industrialization. The beef cattle breeding technologies have rapidly transformed from traditional breeding to molecular marker-assisted breeding, genomic selection and genetic modification breeding. Hundreds of candidate genes and molecular markers associated with growth, meat quality, reproduction performance and diseases resistance have been identified, and some of them have already been used in cattle breeding. Genes and molecular markers associated with growth and development are focused on the growth hormone, muscle regulatory factors, myostatin and insulin-like growth factors. Meat quality is mediated by fatty acid transport and deposition related signals, calpains and calpain system, muscle regulatory factors and muscle growth regulation pathways. Reproduction performance is regulated by GnRH-FSH-LH, growth differentiation factor 9, prolactin receptor and forkhead box protein O1. Disease resistance is modulated by the major histocompatibility complex gene family, toll-like receptors, mannose-binding lectin and interferon gene signals. In this review, we summarize the most recent progress in beef cattle breeding in marker-assisted selection, genome-wide selection and genetic modification breeding, aiming to provide a reference for further genetic breeding research of beef cattle in China.

Use of neural networks to model complex immunogenetic associations of disease: human leukocyte antigen impact on the progression of human immunodeficiency virus infection.

PubMed

Ioannidis, J P; McQueen, P G; Goedert, J J; Kaslow, R A

1998-03-01

Complex immunogenetic associations of disease involving a large number of gene products are difficult to evaluate with traditional statistical methods and may require complex modeling. The authors evaluated the performance of feed-forward backpropagation neural networks in predicting rapid progression to acquired immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus (HIV) infection on the basis of major histocompatibility complex variables. Networks were trained on data from patients from the Multicenter AIDS Cohort Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102). The outcome of interest was rapid disease progression, defined as progression to AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables were selected as network inputs with multivariate regression and a previously described algorithm selecting markers with extreme point estimates for progression risk. Network performance was compared with that of logistic regression. Networks with 15 HLA inputs and a single hidden layer of five nodes achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs. 77.0% and 76.9%, respectively, achieved by logistic regression. When validated on the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of 74.3%, vs. 53.1% and 61.4%, respectively, for logistic regression. Neural networks offer further support to the notion that HIV disease progression may be dependent on complex interactions between different class I and class II alleles and transporters associated with antigen processing variants. The effect in the current models is of moderate magnitude, and more data as well as other host and pathogen variables may need to be considered to improve the performance of the models. Artificial intelligence methods may complement linear statistical methods for evaluating immunogenetic associations of disease.

Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis.

PubMed

Leong, Daniel J; Choudhury, Marwa; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Sun, Hui B

2013-11-21

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals-food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease-offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.

Nutraceuticals: Potential for Chondroprotection and Molecular Targeting of Osteoarthritis

PubMed Central

Leong, Daniel J.; Choudhury, Marwa; Hirsh, David M.; Hardin, John A.; Cobelli, Neil J.; Sun, Hui B.

2013-01-01

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals—food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease—offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment. PMID:24284399

Documentation of medication changes in inpatient clinical notes: an audit to support quality improvement.

PubMed

Peusschers, Elsie; Twine, Jaryth; Wheeler, Amanda; Moudgil, Vikas; Patterson, Sue

2015-04-01

To describe completeness and accuracy of recording medication changes in progress notes during psychiatric inpatient admissions. A retrospective audit of records of 54 randomly selected psychiatric admissions at a metropolitan tertiary hospital. Medication changes recorded on National Inpatient Medication Chart (NIMC) were compared to documentation in the clinical progress records and assessed for completeness against seven quality criteria. With between one and 32 medication changes per admission, a total of 519 changes were recorded in NIMCs. Just over half were documented in progress notes. Psychotropic and regular medications were more frequently charted than 'other' and 'if required' medications. Documentation was seldom comprehensive. Medication name was most frequently documented; desired therapeutic effect or potential adverse effects were rarely documented. Evidence of patient involvement in, and an explicit rationale for, a change were infrequently recorded. Revealing substantial gaps in communication about medication changes during psychiatric admission, this audit sheds light on a previously undescribed source of medication error, warranting attention. Further research is needed to examine barriers to best practice, to support design and implementation of quality improvement activities but in the interim, attention should be addressed to development and articulation of content and procedures for documentation. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Tetrahydrobiopterin Improves Endothelial Function in Cardiovascular Disease: A Systematic Review

PubMed Central

Wang, Qiongying; Yang, Mina; Xu, Han; Yu, Jing

2014-01-01

Background. Tetrahydrobiopterin (BH4) is a cofactor of nitric oxide synthase (NOS). Nitric oxide (NO) bioavailability is reduced during the early stage of vascular diseases, such as coronary artery disease, hypercholesterolemia, hypertension, and diabetic vasculopathy, and even throughout the entire progression of atherosclerosis. Methods. A literature search was performed using electronic databases (up to January 31, 2014), including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), using an established strategy. Results. Fourteen articles were selected with a total of 370 patients. Ten of the fourteen studies showed a significant improvement in the endothelial dysfunction of various cardiovascular disease groups with BH4 supplementation compared with the control groups or placebos. Three studies showed no positive outcome, and one study showed that low-dose BH4 had no effect but that high-dose BH4 did have a significantly different result. Conclusions. This review concludes that supplementation with BH4 and/or augmentation of the endogenous levels of BH4 will be a novel approach to improve the endothelial dysfunction observed in various cardiovascular diseases. BH4 might be considered to be a new therapeutic agent to prevent the initiation and progression of cardiovascular disease. PMID:25548592

Progressively safer, cheaper demolition of Fernald

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

Robert Nichols; Norman Pennington

2000-09-29

Fluor Fernald, Inc. has been progressively improving Decontamination and Dismantlement (D&D) at the Department of Energy's Fernald Environmental Management Project by applying new technologies and better methodologies to the work. Demolition issues existed in the past that necessitated new or improved solutions to maintain worker safety, protect the environment and accomplish the work in a cost effective manner. Lessons learned from D&D of 80 structures has led to a systematic approach, which can be implemented in various D&D arenas. When facility production was halted, hold-up material and process residues remained in the process piping and components. Over 500,000 pounds ofmore » material was removed by workers who completed the tasks two years ahead of schedule, $7 million under budget and with an excellent safety record. This success was the result of detailed planning and irdision of lessons learned as work progressed from facility to facility. Work sequences were developed that reduced airborne contamination. Demolition of structures has been performed at Fernald by carefully selected and qualified subcontractors. Asbestos and lead abatement, equipment, piping and conduit removal, and structural demolition have been completed to progressively higher performance specifications developed by Fluor Fernald based on lessons learned during execution. Safety continues to be the primary consideration in performing potentially hazardous work. Technologies such as hydraulic shears have been developed and used to keep workers away from danger. A new technology, ''Cool Suits,'' has been demonstrated to help prevent heat stress when anti-contamination clothing is required in elevated temperature working conditions. For tall structures, implosion technologies have been employed with progressively improved results, Several other new technologies have been evaluated by Fluor Fernald and applied by subcontractors. The improved technologies included the oxy-gas torch, which uses gasoline instead of acetylene gas, and a vacuum system for asbestos removal of wall insulation. These new methods proved effective and beneficial. Fluor Fernald has integrated demolition activities with waste disposal requirements to enhance overall efficiency. The relatively straight steel configurations required for recycling, and waste acceptance criteria that dictate waste sizes are typically included in the subcontract specifications The progressive improvements by Fluor Fernald have led to cost savings and schedule acceleration without increased risk to workers or the environment. When Fluor Fernald came to the site in 1992, the remediation baseline reflected a completion schedule of 2020 and a cost of $7.2 billion. The current projection is 2008 and $4.2 billion.« less

Comparative Effects of Different Balance-Training–Progression Styles on Postural Control and Ankle Force Production: A Randomized Controlled Trial

PubMed Central

Cuğ, Mutlu; Duncan, Ashley; Wikstrom, Erik

2016-01-01

Context:  Despite the effectiveness of balance training, the exact parameters needed to maximize the benefits of such programs remain unknown. One such factor is how individuals should progress to higher levels of task difficulty within a balance-training program. Yet no investigators have directly compared different balance-training–progression styles. Objective:  To compare an error-based progression (ie, advance when proficient at a task) with a repetition-based progression (ie, advance after a set amount of repetitions) style during a balance-training program in healthy individuals. Design:  Randomized controlled trial. Setting:  Research laboratory. Patients or Other Participants:  A total of 28 (16 women, 12 men) physically healthy young adults (age = 21.57 ± 3.95 years, height = 171.60 ± 11.03 cm, weight = 72.96 ± 16.18 kg, body mass index = 24.53 ± 3.7). Intervention(s):  All participants completed 12 supervised balance-training sessions over 4 weeks. Each session consisted of a combination of dynamic unstable-surface tasks that incorporated a BOSU ball and lasted about 30 minutes. Main Outcome Measure(s):  Static balance from an instrumented force plate, dynamic balance as measured via the Star Excursion Balance Test, and ankle force production in all 4 cardinal planes of motion as measured with a handheld dynamometer before and after the intervention. Results:  Selected static postural-control outcomes, dynamic postural control, and ankle force production in all planes of motion improved (P < .05). However, no differences between the progression styles were observed (P > .05) for any of the outcome measures. Conclusions:  A 4-week balance-training program consisting of dynamic unstable-surface exercises on a BOSU ball improved dynamic postural control and ankle force production in healthy young adults. These results suggest that an error-based balance-training program is comparable with but not superior to a repetition-based balance-training program in improving postural control and ankle force production in healthy young adults. PMID:26878257

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

Imaging multicellular specimens with real-time optimized tiling light-sheet selective plane illumination microscopy

PubMed Central

Fu, Qinyi; Martin, Benjamin L.; Matus, David Q.; Gao, Liang

2016-01-01

Despite the progress made in selective plane illumination microscopy, high-resolution 3D live imaging of multicellular specimens remains challenging. Tiling light-sheet selective plane illumination microscopy (TLS-SPIM) with real-time light-sheet optimization was developed to respond to the challenge. It improves the 3D imaging ability of SPIM in resolving complex structures and optimizes SPIM live imaging performance by using a real-time adjustable tiling light sheet and creating a flexible compromise between spatial and temporal resolution. We demonstrate the 3D live imaging ability of TLS-SPIM by imaging cellular and subcellular behaviours in live C. elegans and zebrafish embryos, and show how TLS-SPIM can facilitate cell biology research in multicellular specimens by studying left-right symmetry breaking behaviour of C. elegans embryos. PMID:27004937

Genetics and genomics of disease resistance in salmonid species

PubMed Central

Yáñez, José M.; Houston, Ross D.; Newman, Scott

2014-01-01

Infectious and parasitic diseases generate large economic losses in salmon farming. A feasible and sustainable alternative to prevent disease outbreaks may be represented by genetic improvement for disease resistance. To include disease resistance into the breeding goal, prior knowledge of the levels of genetic variation for these traits is required. Furthermore, the information from the genetic architecture and molecular factors involved in resistance against diseases may be used to accelerate the genetic progress for these traits. In this regard, marker assisted selection and genomic selection are approaches which incorporate molecular information to increase the accuracy when predicting the genetic merit of selection candidates. In this article we review and discuss key aspects related to disease resistance in salmonid species, from both a genetic and genomic perspective, with emphasis in the applicability of disease resistance traits into breeding programs in salmonids. PMID:25505486

Arrested Hydrocephalus in Childhood: Case Series and Review of the Literature.

PubMed

Hurni, Yannick; Poretti, Andrea; Schneider, Jacques; Guzman, Raphael; Ramelli, Gian Paolo

2018-06-22

 Hydrocephalus can be progressive or spontaneously arrested. In arrested hydrocephalus, the balance between production and absorption of the cerebrospinal fluid is restored. Patients are mostly asymptomatic, and no surgical treatment is necessary for them.  We performed a two-center consecutive case series study, aimed at investigating the safety of nonsurgical management of hydrocephalus in selected pediatric patients. We retrospectively selected all consecutive patients, suspected to suffer from arrested hydrocephalus and referred to our two institutions between January 2011 and December 2013. Data on clinical and radiological follow-up were collected until June 2017.  Five children diagnosed with arrested hydrocephalus were included in the study. All patients presented macrocephaly as the main presenting sign. Associated mild-to-moderate stable motor disorders were assessed in four out of five cases. Typical symptoms and signs associated with acute raised intracranial pressure were absent in all patients. Magnetic resonance imaging studies showed ventriculomegaly in all patients. A diagnosis of arrested hydrocephalus was made in all five cases based on stable clinical and radiological findings during the initial observation. Conservative management based on active surveillance was, therefore, proposed. During the follow-up period, we observed stable or improved conditions in four out of five patients, while the remaining patient presented progressive hydrocephalus.  Making a distinction between arrested and progressive hydrocephalus is fundamental, because of the opposed appropriate management. Any newly discovered case of hydrocephalus, not characterized by clear signs of progressive hydrocephalus, should benefit from active surveillance before any definitive decision is taken. Georg Thieme Verlag KG Stuttgart · New York.

A residency clinic chronic condition management quality improvement project.

PubMed

Halverson, Larry W; Sontheimer, Dan; Duvall, Sharon

2007-02-01

Quality improvement in chronic disease management is a major agenda for improving health and reducing health care costs. A six-component chronic disease management model can help guide this effort. Several characteristics of the "new model" of family medicine described by the Future of Family Medicine (FFM) Project Leadership Committee are promulgated to foster practice changes that improve quality. Our objective was to implement and assess a quality improvement project guided by the components of a chronic disease management model and FFM new model characteristics. Diabetes was selected as a model chronic disease focus. Multiple practice changes were implemented. A mature electronic medical record facilitated data collection and measurement of quality improvement progress. Data from the diabetes registry demonstrates that our efforts have been effective. Significant improvement occurred in five out of six quality indicators. Multidisciplinary teamwork in a model residency practice guided by chronic disease management principles and the FFM new model characteristics can produce significant management improvements in one important chronic disease.

Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico.

PubMed Central

Gutiérrez, G.; Tapia-Conyer, R.; Guiscafré, H.; Reyes, H.; Martínez, H.; Kumate, J.

1996-01-01

Reported are the results of an analysis of mortality trends from diarrhoeal diseases among under-5-year-olds in Mexico between 1978 and 1993 in relation to the impact of education, basic sanitation, and selected medical care practices. The study period was divided into three stages; the first pre-dated the widespread application of oral rehydration therapy (ORT); the second, covered the implementation of a nationwide programme promoting ORT; and the third included additional measures, such as immunization and improvements in basic sanitation. Mortality rates decreased progressively, at an average of 1.8% per year in the first stage, 6.4% in the second, and 17.8% in the third. The importance of literacy campaigns for women and the promotion of ORT was confirmed. Both of these measures reduced mortality; however, a greater reduction resulted from a massive immunization campaign against measles and improvements in sanitation (expansion of the drainage and piped water systems, improved water chlorination procedure, and effective prohibition of the use of sanitary sewage for vegetable irrigation). PMID:8706235

Engineering M13 for phage display.

PubMed

Sidhu, S S

2001-09-01

Phage display is achieved by fusing polypeptide libraries to phage coat proteins. The resulting phage particles display the polypeptides on their surfaces and they also contain the encoding DNA. Library members with particular functions can be isolated with simple selections and polypeptide sequences can be decoded from the encapsulated DNA. The technology's success depends on the efficiency with which polypeptides can be displayed on the phage surface, and significant progress has been made in engineering M13 bacteriophage coat proteins as improved phage display platforms. Functional display has been achieved with all five M13 coat proteins, with both N- and C-terminal fusions. Also, coat protein mutants have been designed and selected to improve the efficiency of heterologous protein display, and in the extreme case, completely artificial coat proteins have been evolved specifically as display platforms. These studies demonstrate that the M13 phage coat is extremely malleable, and this property can be used to engineer the phage particle specifically for phage display. These improvements expand the utility of phage display as a powerful tool in modern biotechnology.

[Vertebral aneurysmatic bone cyst: study of three cases].

PubMed

Vale, Benjamim Pessoa; Alencar, Francisco José; de Aguiar, Guilherme Brasileiro; de Almeida, Bruno Ribeiro

2005-12-01

Aneurysmatic bone cyst is a hypervascularized, benign lesion locally destructive by its progressive growth with greater incidence in the second decade of life. It lodges preferably in the long bones and vertebrae. The clinical picture varies from pain to local edema and even neurological symptoms when in vertebral location. Three cases of vertebral aneurysmatic bone cyst occurring in childhood and all with neurologic deficit symptoms are described. Computerized tomography and/or magnetic resonance imaging confirmed the diagnosis. Patients underwent surgery to remove the tumor. In one of the cases, pre-operative selective arterial embolization of the lesion was performed. The three patients progressed satisfactorily with neurological improvement, which demonstrated the efficiency of the microsurgical technique for the resection of the spinal tumor. The evolution of the cases and the current treatment are discussed.

Selection with inbreeding control in simulated young bull schemes for local dairy cattle breeds.

PubMed

Gandini, G; Stella, A; Del Corvo, M; Jansen, G B

2014-03-01

Local breeds are rarely subject to modern selection techniques; however, selection programs will be required if local breeds are to remain a viable livelihood option for farmers. Selection in small populations needs to take into account accurate inbreeding control. Optimum contribution selection (OCS) is efficient in controlling inbreeding and maximizes genetic gain. The current paper investigates genetic progress in simulated dairy cattle populations from 500 to 6,000 cows undergoing young bull selection schemes with OCS compared with truncation selection (TS) at an annual inbreeding rate of 0.003. Selection is carried out for a dairy trait with a base heritability of 0.3. A young bull selection scheme was used because of its simplicity in implementation. With TS, annual genetic gain from 0.111 standard deviation units with 500 cows increases rapidly to 0.145 standard deviation units with 4,000 cows. Then, genetic gain increases more slowly up to 6,000 cows. At the same inbreeding rate, OCS produces higher genetic progress than TS. Differences in genetic gain between OCS and TS vary from to 2 to 6.3%. Genetic gain is also improved by increasing the number of years that males can be used as sires of sires. When comparing OCS versus TS at different heritabilities, we observe an advantage of OCS only at high heritability, up to 8% with heritability of 0.9. By increasing the constraint on inbreeding, the difference of genetic gain between the 2 selection methods increases in favor of OCS, and the advantage at the inbreeding rate of 0.001 per generation is 6 times more than at the inbreeding rate of 0.003. Opportunities exist for selection even in dairy cattle populations of a few hundred females. In any case, selection in local breeds will most often require specific investments in infrastructure and manpower, including systems for accurate data recording and selection skills and the presence of artificial insemination and breeders organizations. A cost-benefit analysis is therefore advisable before considering the implementation of selection schemes in local dairy cattle breeds. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease.

PubMed

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Ivanenkov, Yan A

2016-03-07

Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, lorazepam, and buspirone in an elevated plus-maze model, elevated platform, and open field tests. The compound demonstrated low toxicity and no side effects in vivo, an appropriate pharmacokinetic profile, and stability. In conclusion, AVN-211 significantly delayed or partially halted the progressive decline in memory function associated with AD, which makes it an interesting drug candidate for the treatment of neurodegenerative and psychiatric disorders. Advanced clinical trials are currently under active discussion and in high priority.

Sperm selection in natural conception: what can we learn from Mother Nature to improve assisted reproduction outcomes?

PubMed Central

Sakkas, Denny; Ramalingam, Mythili; Garrido, Nicolas; Barratt, Christopher L.R.

2015-01-01

BACKGROUND In natural conception only a few sperm cells reach the ampulla or the site of fertilization. This population is a selected group of cells since only motile cells can pass through cervical mucus and gain initial entry into the female reproductive tract. In animals, some studies indicate that the sperm selected by the reproductive tract and recovered from the uterus and the oviducts have higher fertilization rates but this is not a universal finding. Some species show less discrimination in sperm selection and abnormal sperm do arrive at the oviduct. In contrast, assisted reproductive technologies (ART) utilize a more random sperm population. In this review we contrast the journey of the spermatozoon in vivo and in vitro and discuss this in the context of developing new sperm preparation and selection techniques for ART. METHODS A review of the literature examining characteristics of the spermatozoa selected in vivo is compared with recent developments in in vitro selection and preparation methods. Contrasts and similarities are presented. RESULTS AND CONCLUSIONS New technologies are being developed to aid in the diagnosis, preparation and selection of spermatozoa in ART. To date progress has been frustrating and these methods have provided variable benefits in improving outcomes after ART. It is more likely that examining the mechanisms enforced by nature will provide valuable information in regard to sperm selection and preparation techniques in vitro. Identifying the properties of those spermatozoa which do reach the oviduct will also be important for the development of more effective tests of semen quality. In this review we examine the value of sperm selection to see how much guidance for ART can be gleaned from the natural selection processes in vivo. PMID:26386468

Using technology to improve and support communication and workflow processes.

PubMed

Bahlman, Deborah Tuke; Johnson, Fay C

2005-07-01

In conjunction with a large expansion project, a team of perioperative staff members reviewed their workflow processes and designed their ideal patient tracking and communication system. Technologies selected and deployed included a passive infrared tracking system, an enhanced nurse call system, wireless telephones, and a web-based electronic grease board. The new system provides staff members with an easy way to obtain critical pieces of patient information, as well as track the progress of patients and locate equipment.

Innovative Method of Analysis of Actual Cost of Work in Progress

NASA Astrophysics Data System (ADS)

Fil, O.; Terentev, V.

2017-11-01

The article focuses on the basic theory and practical aspects of improving the strategic management in terms of enhancing the quality of a technological process: these aspects have been proven experimentally by their introduction in company operations. The authors have worked out some proposals aimed at selecting an optimal supplier for building companies as well as the algorithm for the analysis and optimization of a construction company basing on scientific and practical research and the experimental data obtained in the experiment

Endoscopic management of benign bile duct strictures.

PubMed

Baron, Todd H; Davee, Tomas

2013-04-01

The use of endoscopic retrograde cholangiopancreatography for treating benign biliary strictures has become the standard of practice, with surgery and percutaneous therapy reserved for selected patients. The gold-standard endoscopic therapy is dilation of the stricture followed by placing and exchanging progressively larger and more numerable plastic stents over a 1-year period. Newer modalities, including the use of fully covered metal stents, are currently under investigation in an effort to improve the treatment of benign biliary strictures. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrating genomic selection into dairy cattle breeding programmes: a review.

PubMed

Bouquet, A; Juga, J

2013-05-01

Extensive genetic progress has been achieved in dairy cattle populations on many traits of economic importance because of efficient breeding programmes. Success of these programmes has relied on progeny testing of the best young males to accurately assess their genetic merit and hence their potential for breeding. Over the last few years, the integration of dense genomic information into statistical tools used to make selection decisions, commonly referred to as genomic selection, has enabled gains in predicting accuracy of breeding values for young animals without own performance. The possibility to select animals at an early stage allows defining new breeding strategies aimed at boosting genetic progress while reducing costs. The first objective of this article was to review methods used to model and optimize breeding schemes integrating genomic selection and to discuss their relative advantages and limitations. The second objective was to summarize the main results and perspectives on the use of genomic selection in practical breeding schemes, on the basis of the example of dairy cattle populations. Two main designs of breeding programmes integrating genomic selection were studied in dairy cattle. Genomic selection can be used either for pre-selecting males to be progeny tested or for selecting males to be used as active sires in the population. The first option produces moderate genetic gains without changing the structure of breeding programmes. The second option leads to large genetic gains, up to double those of conventional schemes because of a major reduction in the mean generation interval, but it requires greater changes in breeding programme structure. The literature suggests that genomic selection becomes more attractive when it is coupled with embryo transfer technologies to further increase selection intensity on the dam-to-sire pathway. The use of genomic information also offers new opportunities to improve preservation of genetic variation. However, recent simulation studies have shown that putting constraints on genomic inbreeding rates for defining optimal contributions of breeding animals could significantly reduce achievable genetic gain. Finally, the article summarizes the potential of genomic selection to include new traits in the breeding goal to meet societal demands regarding animal health and environmental efficiency in animal production.

Use of assisted reproduction for the improvement of milk production in dairy camels (Camelus dromedarius).

PubMed

Nagy, P; Skidmore, J A; Juhasz, J

2013-01-10

Despite their production potential and ability to survive on marginal resources in extreme conditions, dromedaries have not been exploited as an important food source. Camels have not been specifically selected for milk production, and genetic improvement has been negligible. High individual variation in milk production both within the population and within breeds provides a good base for selection and genetic progress. In this paper, we discuss the possibilities and constraints of selective breeding for milk production in camels, and include a summary of the use of embryo transfer at the world's first camel dairy farm. Embryo transfer is an integral part of the breeding strategy at the camel dairy farm because it increases selection intensity and decreases the generation interval. Using high milk-producing camels as donors and low producing camels as recipients, 146 embryos were recovered (6.1±1.0embryos/donor; range: 0-18). Embryos were transferred non-surgically into 111 recipients (83 single and 28 twin embryo transfers). Pregnancy rate at 21 days and 5 months was 55% (61/111) and 45% (50/111), respectively. Finally, a total of 46 recipients delivered a live calf. These results document the utility of embryo transfer using high milk producing dromedaries as donors. Copyright © 2012 Elsevier B.V. All rights reserved.

Retention of membrane charge attributes by cryopreserved-thawed sperm and zeta selection.

PubMed

Kam, Tricia L; Jacobson, John D; Patton, William C; Corselli, Johannah U; Chan, Philip J

2007-09-01

Mature sperm can be selected based on their negative zeta electrokinetic potential. The zeta selection of cryopreserved sperm is unknown. The objective was to study the effect of zeta processing on the morphology and kinematic parameters of cryopreserved-thawed sperm. Colloid-washed sperm (N = 9 cases) were cryopreserved for 24 h, thawed and diluted in serum-free medium in positive-charged tubes. After centrifugation, the tubes were decanted, serum-supplemented medium was added and the resuspended sperm were analyzed. Untreated sperm and fresh sperm served as the controls. There were improvements in strict normal morphology in fresh (11.8 +/- 0.3 versus control 8.8 +/- 0.3 %, mean +/- SEM) and thawed (8.7 +/- 0.2 versus control 5.4 +/- 0.2%) sperm after zeta processing. Percent sperm necrosis was reduced after zeta processing (66.0 +/- 0.6 versus unprocessed 74.6 +/- 0.3%). Progression decreased by 50% but not total motility after zeta processing of thawed sperm. The results suggested that the cryopreservation process did not impact the sperm membrane net zeta potential and higher percentages of sperm with normal strict morphology, acrosome integrity and reduced necrosis were recovered. The zeta method was simple and improved the selection of quality sperm after cryopreservation but more studies would be needed before routine clinical application.

Digital PCR assessment of MGMT promoter methylation coupled with reduced protein expression optimises prediction of response to alkylating agents in metastatic colorectal cancer patients.

PubMed

Sartore-Bianchi, Andrea; Pietrantonio, Filippo; Amatu, Alessio; Milione, Massimo; Cassingena, Andrea; Ghezzi, Silvia; Caporale, Marta; Berenato, Rosa; Falcomatà, Chiara; Pellegrinelli, Alessio; Bardelli, Alberto; Nichelatti, Michele; Tosi, Federica; De Braud, Filippo; Di Nicolantonio, Federica; Barault, Ludovic; Siena, Salvatore

2017-01-01

O(6)-methylguanine-DNA-methyltransferase (MGMT) is a repair protein, and its deficiency makes tumours more susceptible to the cytotoxic effect of alkylating agents. Five clinical trials with temozolomide or dacarbazine have been performed in metastatic colorectal cancer (mCRC) with selection based on methyl-specific PCR (MSP) testing with modest results. We hypothesised that mitigated results are consequences of unspecific patient selection and that alternative methodologies for MGMT testing such as immunohistochemistry (IHC) and digital polymerase chain reaction (PCR) could enhance patient enrolment. Formalin-fixed paraffin embedded archival tumour tissue samples from four phase II studies of temozolomide or dacarbazine in MGMT MSP-positive mCRCs were analysed by IHC for MGMT protein expression and by methyl-BEAMing (MB) for percentage of promoter methylation. Pooled data were then retrospectively analysed according to objective response rate, progression-free survival (PFS) and overall survival (OS). One hundred and five patients were included in the study. Twelve had achieved partial response (PR) (11.4%), 24 stable disease (SD; 22.9%) and 69 progressive disease (PD; 65.7%). Patients with PR/SD had lower IHC scores and higher MB levels than those with PD. MGMT expression by IHC was negatively and MB levels positively associated with PFS (p < 0.001 and 0.004, respectively), but not with OS. By combining both assays, IHC low/MB high patients displayed an 87% reduction in the hazard of progression (p < 0.001) and a 77% in the hazard for death (p = 0.001). In mCRC selected for MGMT deficiency by MSP, IHC and MB testing improve clinical outcome to alkylating agents. Their combination could enhance patient selection in this setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1).

PubMed

Jänne, Pasi A; Mann, Helen; Ghiorghiu, Dana

2016-03-01

Oncogenic KRAS mutations represent the largest genomically defined subset of lung cancer, and are associated with activation of the RAS/RAF/MEK/ERK pathway. There are currently no therapies specifically approved for patients with KRAS-mutant (KRASm) non-small-cell lung cancer (NSCLC), and these patients derive less clinical benefit from chemotherapy than the overall NSCLC population. In a recent phase II study, selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, combined with docetaxel, improved clinical outcome as second-line treatment for patients with KRASm NSCLC. This combination will be further evaluated in the phase III SELECT-1 study. SELECT-1 (NCT01933932) is a randomized, double-blind, placebo-controlled phase III study assessing the efficacy and safety of selumetinib plus docetaxel in patients with KRASm locally advanced or metastatic NSCLC, eligible for second-line treatment. The primary endpoint is progression-free survival (PFS); secondary endpoints include overall survival, objective response rate, duration of response, and safety and tolerability. Approximately 634 patients will be randomized 1:1 to receive selumetinib (75 mg twice daily on a continuous oral administration schedule) in combination with docetaxel (75 mg/m(2), intravenously on day 1 of every 21-day cycle) or placebo in combination with docetaxel (same schedule), until objective disease progression. Patients may continue to receive treatment after objective disease progression if deemed appropriate by the investigator. If the primary endpoint of PFS is met, selumetinib plus docetaxel would be the first targeted treatment for patients with KRASm advanced NSCLC who are eligible for second-line treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Adoptive immunotherapy for the treatment of glioblastoma: progress and possibilities.

PubMed

Kuramitsu, Shunichiro; Yamamichi, Akane; Ohka, Fumiharu; Motomura, Kazuya; Hara, Masahito; Natsume, Atsushi

2016-12-01

Patients with glioblastoma have a very poor prognosis. Adoptive cellular therapy (ACT) is defined as the collection of circulating or tumor-infiltrating lymphocytes, their selection, modification, expansion and activation, and their re-administration to patients in order to induce antitumor activity. Although various ACTs have been attempted, most failed to improve the outcome. Immune checkpoint blockade antibodies and T cell engineering with tumor-specific chimeric antigen receptors suggest the emergence of a new era of immunotherapy. Here, we summarize approaches with ACTs using genetically modified T cells, which have been improved by enhancing their antitumor activity, and discuss strategies to develop these therapies. The mechanisms by which gliomas modulate and evade the immune system are also discussed.

Contrast agents in dynamic contrast-enhanced magnetic resonance imaging

PubMed Central

Yan, Yuling; Sun, Xilin; Shen, Baozhong

2017-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method. PMID:28415647

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

PubMed

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia.

PubMed

Teichmann, Marc; Lesoil, Constance; Godard, Juliette; Vernet, Marine; Bertrand, Anne; Levy, Richard; Dubois, Bruno; Lemoine, Laurie; Truong, Dennis Q; Bikson, Marom; Kas, Aurélie; Valero-Cabré, Antoni

2016-11-01

Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS conditions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating "living"/"nonliving" categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal-excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predominating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left-excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal × living condition. Our findings demonstrate the efficiency of tDCS in sv-PPA by generating highly specific intrasemantic effects. They provide "proof of concept" for future applications of tDCS in therapeutic multiday regimes, potentially driving sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal-pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation. Ann Neurol 2016;80:693-707. © 2016 American Neurological Association.

[Recent advances of anastomosis techniques of esophagojejunostomy after laparoscopic totally gastrectomy in gastric tumor].

PubMed

Li, Xi; Ke, Chongwei

2015-05-01

The esophageal jejunum anastomosis of the digestive tract reconstruction techniques in laparoscopic total gastrectomy includes two categories: circular stapler anastomosis techniques and linear stapler anastomosis techniques. Circular stapler anastomosis techniques include manual anastomosis method, purse string instrument method, Hiki improved special anvil anastomosis technique, the transorally inserted anvil(OrVil(TM)) and reverse puncture device technique. Linear stapler anastomosis techniques include side to side anastomosis technique and Overlap side to side anastomosis technique. Esophageal jejunum anastomosis technique has a wide selection of different technologies with different strengths and the corresponding limitations. This article will introduce research progress of laparoscopic total gastrectomy esophagus jejunum anastomosis from both sides of the development of anastomosis technology and the selection of anastomosis technology.

Research progress of plant population genomics based on high-throughput sequencing.

PubMed

Wang, Yun-sheng

2016-08-01

Population genomics, a new paradigm for population genetics, combine the concepts and techniques of genomics with the theoretical system of population genetics and improve our understanding of microevolution through identification of site-specific effect and genome-wide effects using genome-wide polymorphic sites genotypeing. With the appearance and improvement of the next generation high-throughput sequencing technology, the numbers of plant species with complete genome sequences increased rapidly and large scale resequencing has also been carried out in recent years. Parallel sequencing has also been done in some plant species without complete genome sequences. These studies have greatly promoted the development of population genomics and deepened our understanding of the genetic diversity, level of linking disequilibium, selection effect, demographical history and molecular mechanism of complex traits of relevant plant population at a genomic level. In this review, I briely introduced the concept and research methods of population genomics and summarized the research progress of plant population genomics based on high-throughput sequencing. I also discussed the prospect as well as existing problems of plant population genomics in order to provide references for related studies.

BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE.

PubMed

Roehrborn, Claus G

2008-03-01

Benign prostatic hyperplasia (BPH) represents a significant burden in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a deterioration of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention (AUR) and need for BPH-related surgery. The goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes, to optimize their management. In selected patients, combination of an alpha(1)-blocker and a 5alpha-reductase inhibitor is the most effective form of BPH medical therapy to reduce the risk of clinical progression and relieve LUTS. Monotherapy also significantly reduces the risk of BPH clinical progression, mainly through a reduction of LUTS deterioration for alpha(1)-blockers while 5alpha-reductase inhibitors also reduce the risk of AUR and need for BPH-related surgery. Enlarged prostate and high serum prostate-specific antigen levels have been consistently found to be good clinical predictors of AUR and BPH-related surgery in longitudinal population-based studies and placebo arms of controlled studies. High post-void residual urine (PVR) is also associated with an increased risk of LUTS deterioration and should thus be reconsidered in practice as a predictor of BPH progression. Conversely, baseline LUTS severity and low peak flow rate, initially identified as predictors of unfavourable outcomes in community setting, behave paradoxically in controlled trials, probably as a consequence of strict inclusion criteria and subsequent regression to the mean and glass ceiling effects. Lastly, there is increasing evidence that dynamic variables, such as LUTS and PVR worsening, and lack of symptomatic improvement with alpha(1)-blockers are important predictors of future LUTS/BPH-related events, allowing better identification and management of patients at risk of BPH progression.

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

Explaining equity gains in child survival in Bangladesh: scale, speed, and selectivity in health and development.

PubMed

Adams, Alayne M; Rabbani, Atonu; Ahmed, Shamim; Mahmood, Shehrin Shaila; Al-Sabir, Ahmed; Rashid, Sabina F; Evans, Timothy G

2013-12-14

By disaggregating gains in child health in Bangladesh over the past several decades, significant improvements in gender and socioeconomic inequities have been revealed. With the use of a social determinants of health approach, key features of the country's development experience can be identified that help explain its unexpected health trajectory. The systematic equity orientation of health and socioeconomic development in Bangladesh, and the implementation attributes of scale, speed, and selectivity, have been important drivers of health improvement. Despite this impressive pro-equity trajectory, there remain significant residual inequities in survival of girls and lower wealth quintiles as well as a host of new health and development challenges such as urbanisation, chronic disease, and climate change. Further progress in sustaining and enhancing equity-oriented achievements in health hinges on stronger governance and longer-term systems thinking regarding how to effectively promote inclusive and equitable development within and beyond the health system. Copyright © 2013 Elsevier Ltd. All rights reserved.

A multicenter collaborative approach to reducing pediatric codes outside the ICU.

PubMed

Hayes, Leslie W; Dobyns, Emily L; DiGiovine, Bruno; Brown, Ann-Marie; Jacobson, Sharon; Randall, Kelly H; Wathen, Beth; Richard, Heather; Schwab, Carolyn; Duncan, Kathy D; Thrasher, Jodi; Logsdon, Tina R; Hall, Matthew; Markovitz, Barry

2012-03-01

The Child Health Corporation of America formed a multicenter collaborative to decrease the rate of pediatric codes outside the ICU by 50%, double the days between these events, and improve the patient safety culture scores by 5 percentage points. A multidisciplinary pediatric advisory panel developed a comprehensive change package of process improvement strategies and measures for tracking progress. Learning sessions, conference calls, and data submission facilitated collaborative group learning and implementation. Twenty Child Health Corporation of America hospitals participated in this 12-month improvement project. Each hospital identified at least 1 noncritical care target unit in which to implement selected elements of the change package. Strategies to improve prevention, detection, and correction of the deteriorating patient ranged from relatively simple, foundational changes to more complex, advanced changes. Each hospital selected a broad range of change package elements for implementation using rapid-cycle methodologies. The primary outcome measure was reduction in codes per 1000 patient days. Secondary outcomes were days between codes and change in patient safety culture scores. Code rate for the collaborative did not decrease significantly (3% decrease). Twelve hospitals reported additional data after the collaborative and saw significant improvement in code rates (24% decrease). Patient safety culture scores improved by 4.5% to 8.5%. A complex process, such as patient deterioration, requires sufficient time and effort to achieve improved outcomes and create a deeply embedded culture of patient safety. The collaborative model can accelerate improvements achieved by individual institutions.

Quantitative Determination of Technological Improvement from Patent Data

PubMed Central

2015-01-01

The results in this paper establish that information contained in patents in a technological domain is strongly correlated with the rate of technological progress in that domain. The importance of patents in a domain, the recency of patents in a domain and the immediacy of patents in a domain are all strongly correlated with increases in the rate of performance improvement in the domain of interest. A patent metric that combines both importance and immediacy is not only highly correlated (r = 0.76, p = 2.6*10-6) with the performance improvement rate but the correlation is also very robust to domain selection and appears to have good predictive power for more than ten years into the future. Linear regressions with all three causal concepts indicate realistic value in practical use to estimate the important performance improvement rate of a technological domain. PMID:25874447

All chain Loran-C time synchronization

NASA Technical Reports Server (NTRS)

Sherman, H. T.

1973-01-01

A program is in progress to implement coordinated universal time (UTC) synchronization on all Loran-C transmissions. The present capability is limited to five Loran-C chains in which the tolerance is twenty-five microseconds with respect to UTC. Upon completion of the program, the transmissions of all Loran-C chains will be maintained within five microseconds of UTC. The improvement plan consists of equipping selected Loran-C transmitting stations for greater precision of frequency standard adjustment and improved monitoring capability. External time monitor stations will utilize television time transfer techniques with nearby SATCOM terminals where practicable, thus providing the requisite traceability to the Naval Observatory. The monitor equipment groups and the interrelationships with the ground station equipment are discussed. After a brief review of control doctrine, forth-coming improvements to transmitting stations and how the time monitor and navigation equipments will complement each other resulting in improved service to all users of the Loran-C system are described.

Design of a new therapy for patients with chronic kidney disease: use of microarrays for selective hemoadsorption of uremic wastes and toxins to improve homeostasis.

PubMed

Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

2015-01-01

The hypothesis proposed here would provide near to optimum homeostasis for patients with chronic kidney disease (CKD) without the need for hemodialysis. This strategy has not been described previously in the scientific literature. It involves a targeted therapy that may prevent progression of the disease and help to improve the well-being of CKD patients. It proposes a nanotechnological device, ie, a microarray-oriented homeostasis provider (MOHP), to improve homeostasis in CKD patients. MOHP would be an auxiliary kidney aid, and would improve the filtration functions that impaired kidneys cannot perform by their own. MOHP is composed of two main computer-oriented components, ie, a quantitative microarray detector (QMD) and a homeostasis-oriented microarray column (HOMC). QMD detects and HOMC selectively removes defined quantities of uremic wastes, toxins and any other metabolites which is programmed for. The QMD and HOMC would accomplish this with the help of a peristaltic blood pump that would circulate blood aseptically in an extracorporeal closed circuit. During the passage of blood through the QMD, this microarray detector would quantitatively monitor all of the blood compounds that accumulate in the blood of a patient with impaired glomerular filtration, including small-sized, middle-sized and large-sized molecules. The electronic information collected by QMD would be electronically transmitted to the HOMC, which would adjust the molecules to the concentrations they are electronically programmed for and/or receive from QMD. This process of monitoring and removal of waste continues until the programmed homeostasis criteria are reached. Like a conventional kidney machine, MOHP can be used in hospitals and homes under the supervision of a trained technician. The main advantages of this treatment would include improved homeostasis, a reduced likelihood of side effects and of the morbidity resulting from CKD, slower progression of kidney impairment, prevention of end-stage renal failure, a decreased need for hemodialysis therapy, avoidance of dialysis-related side effects later on in the patient's life, improved quality of life and increased life expectancy.

Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

PubMed

Cancedda, Simona; Sabattini, Silvia; Bettini, Giuliano; Leone, Vito F; Laganga, Paola; Rossi, Federica; Terragni, Rossella; Gnudi, Giacomo; Vignoli, Massimo

2015-01-01

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas. © 2015 American College of Veterinary Radiology.

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

From near-infrared and Raman to surface-enhanced Raman spectroscopy: progress, limitations and perspectives in bioanalysis.

PubMed

Dumont, Elodie; De Bleye, Charlotte; Sacré, Pierre-Yves; Netchacovitch, Lauranne; Hubert, Philippe; Ziemons, Eric

2016-05-01

Over recent decades, spreading environmental concern entailed the expansion of green chemistry analytical tools. Vibrational spectroscopy, belonging to this class of analytical tool, is particularly interesting taking into account its numerous advantages such as fast data acquisition and no sample preparation. In this context, near-infrared, Raman and mainly surface-enhanced Raman spectroscopy (SERS) have thus gained interest in many fields including bioanalysis. The two former techniques only ensure the analysis of concentrated compounds in simple matrices, whereas the emergence of SERS improved the performances of vibrational spectroscopy to very sensitive and selective analyses. Complex SERS substrates were also developed enabling biomarker measurements, paving the way for SERS immunoassays. Therefore, in this paper, the strengths and weaknesses of these techniques will be highlighted with a focus on recent progress.

Recent progresses in outcome-dependent sampling with failure time data.

PubMed

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2017-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case-cohort design, generalized case-cohort design, stratified case-cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design.

Recent progresses in outcome-dependent sampling with failure time data

PubMed Central

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2016-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case–cohort design, generalized case–cohort design, stratified case–cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design. PMID:26759313

Tools for probing local circuits: high-density silicon probes combined with optogenetics

PubMed Central

Buzsáki, György; Stark, Eran; Berényi, Antal; Khodagholy, Dion; Kipke, Daryl R.; Yoon, Euisik; Wise, Kensall

2015-01-01

To understand how function arises from the interactions between neurons, it is necessary to use methods that allow the monitoring of brain activity at the single-neuron, single-spike level and the targeted manipulation of the diverse neuron types selectively in a closed-loop manner. Large-scale recordings of neuronal spiking combined with optogenetic perturbation of identified individual neurons has emerged as a suitable method for such tasks in behaving animals. To fully exploit the potential power of these methods, multiple steps of technical innovation are needed. We highlight the current state-of-the-art in electrophysiological recording methods, combined with optogenetics, and discuss directions for progress. In addition, we point to areas where rapid development is in progress and discuss topics where near-term improvements are possible and needed. PMID:25856489

Genomic Selection Improves Heat Tolerance in Dairy Cattle

PubMed Central

Garner, J. B.; Douglas, M. L.; Williams, S. R. O; Wales, W. J.; Marett, L. C.; Nguyen, T. T. T.; Reich, C. M.; Hayes, B. J.

2016-01-01

Dairy products are a key source of valuable proteins and fats for many millions of people worldwide. Dairy cattle are highly susceptible to heat-stress induced decline in milk production, and as the frequency and duration of heat-stress events increases, the long term security of nutrition from dairy products is threatened. Identification of dairy cattle more tolerant of heat stress conditions would be an important progression towards breeding better adapted dairy herds to future climates. Breeding for heat tolerance could be accelerated with genomic selection, using genome wide DNA markers that predict tolerance to heat stress. Here we demonstrate the value of genomic predictions for heat tolerance in cohorts of Holstein cows predicted to be heat tolerant and heat susceptible using controlled-climate chambers simulating a moderate heatwave event. Not only was the heat challenge stimulated decline in milk production less in cows genomically predicted to be heat-tolerant, physiological indicators such as rectal and intra-vaginal temperatures had reduced increases over the 4 day heat challenge. This demonstrates that genomic selection for heat tolerance in dairy cattle is a step towards securing a valuable source of nutrition and improving animal welfare facing a future with predicted increases in heat stress events. PMID:27682591

Application of a web-based cognitive-behavioural therapy programme for the treatment of selective mutism in Singapore: a case series study.

PubMed

Ooi, Yoon Phaik; Raja, Malini; Sung, Sharon Cohan; Fung, Daniel S S; Koh, Jessie B K

2012-07-01

Selective mutism (SM) is characterised by limited or a lack of speech in selected social settings. Recent reviews suggest that cognitive-behavioural therapy (CBT) is an effective and promising treatment approach for SM. However, there is still a lack of studies documenting the applicability of CBT for SM in diverse populations. The goal of the present study was to examine the use of a web-based CBT programme ('Meeky Mouse') among Singaporean children diagnosed with SM. Five children with SM (one boy and four girls aged 6-11 years) participated in the 14-week 'Meeky Mouse' programme, in addition to being prescribed with an unchanged dosage of fluoxetine 10-20 mg daily. The progress made by the children throughout the course of the programme was documented by the therapist. Post treatment, four out of the five children demonstrated improvements in the frequency of speech during therapy sessions at home, in school and at other social situations. Findings from the present study provide support for the use of a web-based CBT programme in improving speech and decreasing the severity of SM among affected children.

Delta Opioid Receptor (DOR) Ligands and Pharmacology: Development of Indolo- and Quinolinomorphinan Derivatives Based on the Message-Address Concept.

PubMed

Saitoh, Akiyoshi; Nagase, Hiroshi

2016-10-28

The pharmacology of the delta opioid receptor (DOR) has lagged, mainly due to the lack of an agonist with high potency and selectivity in vivo. The DOR is now receiving increasing attention, and there has been progress in the synthesis of better novel ligands. The discovery of a selective receptor DOR antagonist, naltrindole (NTI), stimulated the design and synthesis of (±)TAN-67, which was designed based on the message-address concept and the accessory site theory. Intensive studies using (±)TAN-67 determined the DOR-mediated various pharmacological effects, such as antinociceptive effects for painful diabetic neuropathy and cardiovascular protective effects. We improved the agonist activity of TAN-67 to afford SN-28, which was modified to KNT-127, a novel compound that improved the blood-brain barrier permeability. In addition, KNT-127 showed higher selectivity for the DOR and had potent agonist activity following systemic administration. Interestingly, KNT-127 produced no convulsive effects, unlike prototype DOR agonists. The KNT-127 type derivatives with a quinolinomorphinan structure are expected to be promising candidates for the development of therapeutic DOR agonists.

A review of human biomonitoring in selected Southeast Asian countries.

PubMed

Barnett-Itzhaki, Zohar; Esteban López, Marta; Puttaswamy, Naveen; Berman, Tamar

2018-07-01

Rapid development and industrialization in Southeast (SE) Asia has led to environmental pollution, potentially exposing the general population to environmental contaminants. Human biomonitoring (HBM), measurement of chemical and/or their metabolites in human tissues and fluids, is an important tool for assessing cumulative exposure to complex mixtures of chemicals and for monitoring chemical exposures in the general population. While there are national HBM programs in several developed countries, there are no such national programs in most of the SE Asian countries. However, in recent years there has been progress in the field of HBM in many of the SE Asian countries. In this review, we present recent HBM studies in five selected SE Asian countries: Bangladesh, Indonesia, Malaysia, Myanmar and Thailand. While there is extensive HBM research in several SE Asian countries, such as Thailand, in other countries HBM studies are limited and focus on traditional environmental pollutants (such as lead, arsenic and mercury). Further development of this field in SE Asia would be benefited by establishment of laboratory capacity, improving quality control and assurance, collaboration with international experts and consortiums, and sharing of protocols and training both for pre-analytical and analytical phases. This review highlights the impressive progress in HBM research in selected SE Asian countries and provides recommendations for development of this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing

PubMed Central

Casanova, Manuel F.

2014-01-01

The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-cortical interactions between interlaminar prefrontal cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer’s and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving cortical minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders. PMID:24531625

Relationship between Admission Selection Criteria and Academic Progression for Student Nurse Anesthetists

ERIC Educational Resources Information Center

Burns, Sharon M.

2009-01-01

Today's admission selection criteria require refinement with the intention of fostering academic progression for students entering nurse anesthesia programs (Reese, 2002).With the escalating cost of graduate education coupled with the current economic crisis, efforts by educational leaders to minimize attrition remains pivotal (Andrews, Johansson,…

Progress in increasing affordability of medicines for non-communicable diseases since the introduction of mandatory health insurance in the Republic of Moldova.

PubMed

Ferrario, Alessandra; Chitan, Elena; Seicas, Rita; Sautenkova, Nina; Bezverhni, Zinaida; Kluge, Hans; Habicht, Jarno

2016-07-01

To assess progress in improving affordability of medicines since the introduction of mandatory health insurance in the Republic of Moldova. 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. 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. 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. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.

PubMed

Liu, Youhong; Liu, Yijun; Yuan, Bowen; Yin, Linglong; Peng, Yuchong; Yu, Xiaohui; Zhou, Weibing; Gong, Zhicheng; Liu, Jianye; He, Leye; Li, Xiong

2017-03-07

Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.

Progressive sampling-based Bayesian optimization for efficient and automatic machine learning model selection.

PubMed

Zeng, Xueqiang; Luo, Gang

2017-12-01

Machine learning is broadly used for clinical data analysis. Before training a model, a machine learning algorithm must be selected. Also, the values of one or more model parameters termed hyper-parameters must be set. Selecting algorithms and hyper-parameter values requires advanced machine learning knowledge and many labor-intensive manual iterations. To lower the bar to machine learning, miscellaneous automatic selection methods for algorithms and/or hyper-parameter values have been proposed. Existing automatic selection methods are inefficient on large data sets. This poses a challenge for using machine learning in the clinical big data era. To address the challenge, this paper presents progressive sampling-based Bayesian optimization, an efficient and automatic selection method for both algorithms and hyper-parameter values. We report an implementation of the method. We show that compared to a state of the art automatic selection method, our method can significantly reduce search time, classification error rate, and standard deviation of error rate due to randomization. This is major progress towards enabling fast turnaround in identifying high-quality solutions required by many machine learning-based clinical data analysis tasks.

On The Relationship between Suspended Solids of Different Size, the Observed Boundary Flux and Rejection Values for Membranes Treating a Civil Wastewater Stream.

PubMed

Stoller, Marco; Pulido, Javier Miguel Ochando; Palma, Luca Di

2014-08-04

Membrane fouling is one of the main issues in membrane processes, leading to a progressive decrease of permeability. High fouling rates strongly reduce the productivity of the membrane plant, and negatively affect the surviving rate of the membrane modules, especially when real wastewater is treated. On the other hand, since selectivity must meet certain target requirements, fouling may lead to unexpected selectivity improvements due to the formation of an additional superficial layer formed of foulants and that act like a selective secondary membrane layer. In this case, a certain amount of fouling may be profitable to the point where selectivity targets were reached and productivity is not significantly affected. In this work, the secondary clarifier of a step sludge recirculation bioreactor treating municipal wastewater was replaced by a membrane unit, aiming at recovering return sludge and producing purified water. Fouling issues of such a system were checked by boundary flux measurements. A simple model for the description of the observed productivity and selectivity values as a function of membrane fouling is proposed.

On The Relationship between Suspended Solids of Different Size, the Observed Boundary Flux and Rejection Values for Membranes Treating a Civil Wastewater Stream

PubMed Central

Stoller, Marco; Pulido, Javier Miguel Ochando; Di Palma, Luca

2014-01-01

Membrane fouling is one of the main issues in membrane processes, leading to a progressive decrease of permeability. High fouling rates strongly reduce the productivity of the membrane plant, and negatively affect the surviving rate of the membrane modules, especially when real wastewater is treated. On the other hand, since selectivity must meet certain target requirements, fouling may lead to unexpected selectivity improvements due to the formation of an additional superficial layer formed of foulants and that act like a selective secondary membrane layer. In this case, a certain amount of fouling may be profitable to the point where selectivity targets were reached and productivity is not significantly affected. In this work, the secondary clarifier of a step sludge recirculation bioreactor treating municipal wastewater was replaced by a membrane unit, aiming at recovering return sludge and producing purified water. Fouling issues of such a system were checked by boundary flux measurements. A simple model for the description of the observed productivity and selectivity values as a function of membrane fouling is proposed. PMID:25093867

Progress in modification of sunflower oil to expand its industrial value.

PubMed

Rauf, Saeed; Jamil, Nazia; Tariq, Sultan Ali; Khan, Maria; Kausar, Maria; Kaya, Yalcin

2017-05-01

Increasing the sunflower seed oil content as well as improving its quality makes it compatible for industrial demands. This is an important breeding objective of sunflower which increases its market value and ensures high returns for the producers. The present review focuses on determining the progress of improving sunflower seed oil content and modifying its quality by empirical and advanced molecular breeding methods. It is known that the sunflower oil content and quality have been altered through empirical selection methods and mutation breeding programmes in various parts of the world. Further improvement in seed oil content and its components (such as phytosterols, tocopherols and modified fatty acid profile) has been slowed down due to low genetic variation in elite germplasm and complex of hereditary traits. Introgression from wild species can be carried out to modify the fatty acids profile and tocopherol contents with linkage drags. Different transgenes introduced through biotechnological methods may produce novel long-chain fatty acids within sunflower oil. Bio-engineering of sunflower oil could allow it to be used in diverse industrial products such as bio-diesel or bio-plastics. These results showed that past and current trends of modifying sunflower oil quality are essential for its further expansion as an oilseed crop. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

A review on breeding and genetic strategies in Iranian buffaloes (Bubalus bubalis).

PubMed

Safari, Abbas; Ghavi Hossein-Zadeh, Navid; Shadparvar, Abdol Ahad; Abdollahi Arpanahi, Rostam

2018-04-01

The aim of current study was to review breeding progress and update information on genetic strategies in Iranian buffaloes. Iranian buffalo is one of the vital domestic animals throughout north, north-west, south and south-west of Iran with measurable characteristics both in milk and meat production. The species plays an important role in rural economy of the country due to its unique characteristics such as resistance to diseases and parasites, having long productive lifespan and showing higher capability of consuming low-quality forage. In Iran, total production of milk and meat devoted to buffaloes are 293,000 and 24,700 tons, respectively. Selection activities and milk yield recording are carrying out by the central government through the Animal Breeding Centre of Iran. The main breeding activities of Iranian buffaloes included the estimation of genetic parameters and genetic trends for performance traits using different models and methods, estimation of economic values and selection criteria and analysis of population structure. Incorporating different aspects of dairy buffalo management together with improved housing, nutrition, breeding and milking, is known to produce significant improvements in buffalo production. Therefore, identifying genetic potential of Iranian buffaloes, selection of superior breeds, improving nutritional management and reproduction and developing the education and increasing the skills of practical breeders can be useful in order to enhance the performance and profitability of Iranian buffaloes.

TAM Receptor Tyrosine Kinases in Cancer Drug Resistance.

PubMed

Vouri, Mikaella; Hafizi, Sassan

2017-06-01

Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy. As chemoresistance is the leading cause of cancer spread, progression, and mortality, there is an increasing need for understanding the mechanisms by which cancer cells can evade therapy-induced cell death. The TAM (Tyro3, Axl, Mer) subfamily of RTKs in particular feature in a variety of cancer types that have developed resistance to a broad range of therapeutic agents, including both targeted as well as conventional chemotherapeutics. This article reviews the roles of TAMs as tumor drivers and as mediators of chemoresistance, and the potential effectiveness of targeting them as part of therapeutic strategies to delay or combat resistance. Cancer Res; 77(11); 2775-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

PubMed

Kutushov, M; Gorelik, O

2013-01-01

Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

A model for rigorously applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework in the design and measurement of a large scale collaborative multi-site study.

PubMed

Becan, Jennifer E; Bartkowski, John P; Knight, Danica K; Wiley, Tisha R A; DiClemente, Ralph; Ducharme, Lori; Welsh, Wayne N; Bowser, Diana; McCollister, Kathryn; Hiller, Matthew; Spaulding, Anne C; Flynn, Patrick M; Swartzendruber, Andrea; Dickson, Megan F; Fisher, Jacqueline Horan; Aarons, Gregory A

2018-04-13

This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. NCT02672150 . Retrospectively registered on 22 January 2016.

Differential Deposition for Surface Figure Corrections in Grazing Incidence X-Ray Optics

NASA Technical Reports Server (NTRS)

Ramsey, Brian D.; Kilaru, Kiranmayee; Atkins, Carolyn; Gubarev, Mikhail V.; Broadway, David M.

2015-01-01

Differential deposition corrects the low- and mid- spatial-frequency deviations in the axial figure of Wolter-type grazing incidence X-ray optics. Figure deviations is one of the major contributors to the achievable angular resolution. Minimizing figure errors can significantly improve the imaging quality of X-ray optics. Material of varying thickness is selectively deposited, using DC magnetron sputtering, along the length of optic to minimize figure deviations. Custom vacuum chambers are built that can incorporate full-shell and segmented Xray optics. Metrology data of preliminary corrections on a single meridian of full-shell x-ray optics show an improvement of mid-spatial frequencies from 6.7 to 1.8 arc secs HPD. Efforts are in progress to correct a full-shell and segmented optics and to verify angular-resolution improvement with X-ray testing.

Progressive Spinal Kyphosis in the Aging Population.

PubMed

Ailon, Tamir; Shaffrey, Christopher I; Lenke, Lawrence G; Harrop, James S; Smith, Justin S

2015-10-01

Thoracic kyphosis tends to increase with age. Hyperkyphosis is defined as excessive curvature of the thoracic spine and may be associated with adverse health effects. Hyperkyphosis in isolation or as a component of degenerative kyphoscoliosis has important implications for the surgical management of adult spinal deformity. Our objective was to review the literature on the epidemiology, etiology, natural history, management, and outcomes of thoracic hyperkyphosis. We performed a narrative review of literature on thoracic hyperkyphosis and its implications for adult spinal deformity surgery. Hyperkyphosis has a prevalence of 20% to 40% and is more common in the geriatric population. The cause is multifactorial and involves an interaction between degenerative changes, vertebral compression fractures, muscular weakness, and altered biomechanics. It may be associated with adverse health consequences including impaired physical function, pain and disability, impaired pulmonary function, and increased mortality. Nonoperative management may slow the progression of kyphosis and improve function. Surgery is rarely performed for isolated hyperkyphosis in the elderly due to the associated risk, but is an option when kyphosis occurs in the context of significant deformity. In this scenario, increased thoracic kyphosis influences selection of fusion levels and overall surgical planning. Kyphosis is common in older individuals and is associated with adverse health effects and increased mortality. Current evidence suggests a role for nonoperative therapies in reducing kyphosis and delaying its progression. Isolated hyperkyphosis in the elderly is rarely treated surgically; however, increased thoracic kyphosis as a component of global spinal deformity has important implications for patient selection and operative planning.

Improved conversion of herbaceous biomass to biofuels: Potential for modification of key plant characteristics

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

Sladden, S.E.; Bransby, D.I.

1989-10-01

Biomass crops are converted to fuels via biochemical and thermochemical processes. The process preferred depends on properties and cost of available feedstocks, and on the specific products desired. Since most mature biomass crops are composed of up to 80% cell wall fibers, the properties of these fibers determine, to a large degree, the conversion potential of the crop. However, biomass crops also contain small amounts of proteins, soluble carbohydrates and interfering materials (e.g., tannins and silica) which also influence the desirability of the feedstock in specific conversion processes. Fortunately, wide variation exists in the chemical composition of potential biomass crops.more » Although the chemical composition of feedstocks can be influenced significantly with judicious management has species selection, some traits are sufficiently heritable to permit breeding for improved feedstock composition. In addition to breeding for specific compositional traits directly, selection for in vitro digestibility or for easily-measured canopy or physiological traits may lead to more rapid and efficient progress in feedstock improvement, provided those measurements are highly-correlated with desirable feedstock composition. At the same time breeders must improve, or at least avoid damaging, stand longevity, tendency of plants to lodge, and establishment traits (e.g., disease resistance and seedling vigor). 46 refs., 8 tabs.« less

Drought tolerance in potato (S. tuberosum L.): Can we learn from drought tolerance research in cereals?

PubMed

Monneveux, Philippe; Ramírez, David A; Pino, María-Teresa

2013-05-01

Drought tolerance is a complex trait of increasing importance in potato. Our knowledge is summarized concerning drought tolerance and water use efficiency in this crop. We describe the effects of water restriction on physiological characteristics, examine the main traits involved, report the attempts to improve drought tolerance through in vitro screening and marker assisted selection, list the main genes involved and analyze the potential interest of native and wild potatoes to improve drought tolerance. Drought tolerance has received more attention in cereals than in potato. The review compares these crops for indirect selection methods available for assessment of drought tolerance related traits, use of genetic resources, progress in genomics, application of water saving techniques and availability of models to anticipate the effects of climate change on yield. It is concluded that drought tolerance improvement in potato could greatly benefit from the transfer of research achievements in cereals. Several promising research directions are presented, such as the use of fluorescence, reflectance, color and thermal imaging and stable isotope techniques to assess drought tolerance related traits, the application of the partial root-zone drying technique to improve efficiency of water supply and the exploitation of stressful memory to enhance hardiness. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Phase 2 synopsis, and NASA will provide that source to all the material furnished to the Phase 1... the date upon which Phase 2 proposals are requested. Any such changes in evaluation factors will not... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Phase 2 synopsis, and NASA will provide that source to all the material furnished to the Phase 1... the date upon which Phase 2 proposals are requested. Any such changes in evaluation factors will not... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

Implementation Planning and Progress on Physical Activity Goals: The Mediating Role of Life-Management Strategies

ERIC Educational Resources Information Center

Dugas, Michelle; Gaudreau, Patrick; Carraro, Natasha

2012-01-01

This 4-week prospective study examined whether the use of life-management strategies mediates the relationship between implementation planning and short-term progress on physical activity goals. In particular, the strategies of elective selection, compensation, and loss-based selection were disentangled to assess their specific mediating effects.…

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

[Environmental health and inequalities: building indicators for sustainable development].

PubMed

Carneiro, Fernando Ferreira; Franco Netto, Guilherme; Corvalan, Carlos; de Freitas, Carlos Machado; Sales, Luiz Belino Ferreira

2012-06-01

Despite its progress in terms of socio-economic indicators, Brazil is still unequal, which is due to an unequal and exclusionary historical process. In this paper we selected the Human Development Index - HDI and other social, economic, environmental and health indicators to exemplify this situation. We selected the municipalities that had the lowest HDI in the country in 2000 comparing their evolution over time between 2000 and 2010 by means of indicators linked to the economic, environmental and social pillars of sustainable development. These municipalities have an HDI classified as low (<0.500), and correspond to countries such as Laos, Yemen, Haiti and Madagascar. At national level, data for the decade show a significant improvement in economic indicators (decrease from 23% to 8.9% of people living on less than a quarter of the minimum wage); social indicators (increase from 86.5% to 90.2% of literacy in women), and the environmental indicator associated with access to the water grid, which also improved to a lesser extent (increase from 81% to 85%). It was concluded that in order to achieve sustainable development with quality of life, the improvement of sanitation and education indicators should be a priority for Brazil.

Selected Topics in CVD Diamond Research

NASA Astrophysics Data System (ADS)

Koizumi, Satoshi; Nebel, Christoph E.; Nesladek, Milos

2006-10-01

Since the discovery of Chemical Vapor Deposition (CVD) diamond growth in 1976, the steady scientific progress often resulted in surprising new discoveries and breakthroughs. This brought us to the idea to publish the special issue Selected Topics in CVD Diamond Research in physica status solidi (a), reflecting such advancements and interesting results at the leading edge of diamond research.The present issue summarizes this progress in the CVD diamond field by selecting contributions from several areas such as superconductivity, super-excitonic radiation, quantum computing, bio-functionalization, surface electronic properties, the nature of phosphorus doping, transport properties in high energy detectors, CVD growth and properties of nanocrystalline diamond. In all these directions CVD diamond appears to be very competitive in comparison with other semiconducting materials.As Editors of this special issue, we must admit that the selection is biased by our opinion. Nonetheless, we are sure that each contribution introduces new ideas and results which will improve the understanding of the current level of physics and chemistry of this attractive wide-bandgap semiconductor and which will help to bring it closer to applications.All submissions were invited based on the contributions of the authors to their specific research field. The Feature Articles have the format of topical reviews to give the reader a comprehensive summary. Partially, however, they are written in research paper style to report new results of ongoing research.We hope that this issue will attract the attention of a broad community of scientists and engineers, and that it will facilitate the utilization of diamond in electronic applications and technologies of the future.

Patients with ALS show highly correlated progression rates in left and right limb muscles.

PubMed

Rushton, David J; Andres, Patricia L; Allred, Peggy; Baloh, Robert H; Svendsen, Clive N

2017-07-11

Amyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression. A large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb. This report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent. First, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

FGFR-targeted therapeutics for the treatment of breast cancer.

PubMed

De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

2017-03-01

Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

Rehabilitation Tool

NASA Technical Reports Server (NTRS)

1993-01-01

Biotran, or Fastex as named by Cybex, the company that manufactures it, is a force sensing system that helps physicians and physical therapists treat people with movement deficiencies. Based on NASA sensor technology, it also has applications in sports training and evaluation. Biotran provides a means of testing weight-bearing capabilities that may have been compromised by injury or disease. It also assists in the rehabilitation process by putting patients through a course of computer-directed exercises designed to improve strength and balance reaction time. The system tests and documents progress until maximum medical improvement is achieved. Lewis Research Center also assisted the company in the selection of the material used in the Biotran force sensing platforms. Biotran is currently manufactured by Cybex under the name Fastex.

Student continuation in high school chemistry

NASA Astrophysics Data System (ADS)

Bowen, James Iddon

2006-12-01

This investigation originally intended to uncover teacher behaviors that encourage students to persist in AP Chemistry in a typical urban Texas high school. As the investigation progressed, however, alternative reasons were sought for the persistence of some students when it became apparent that teacher behaviors might not be a factor in the decision to select AP Chemistry at the school under observation. In response to this, "Branding", a business theory which suggests certain attractive aspects of a product are promoted as a way to improve sales, is introduced as an alternative way of thinking about persistence in chemistry. "Branding" can explain why some students continue to select chemistry in the face of disappointing teaching. It is also argued here that "Branding" can encourage more students to take chemistry in the future.

A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

PubMed

Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

2017-09-01

Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

Icotinib, a selective EGF receptor tyrosine kinase inhibitor, for the treatment of non-small-cell lung cancer.

PubMed

Tan, Fenlai; Shi, Yuankai; Wang, Yinxiang; Ding, Lieming; Yuan, Xiaobin; Sun, Yan

2015-01-01

Advanced non-small-cell lung cancer (NSCLC) is the main cause for cancer-related mortality. Treatments for advanced NSCLC are largely palliative and a benefit plateau appears to have reached with the platinum-based chemotherapy regimens. EGF receptor (EGFR) tyrosine kinase inhibitors gefitinib, erlotinib and afatinib came up with prolonged progression-free survival and improved quality of life, especially in EGFR-mutated patients. Icotinib is an oral selective EGFR tyrosine kinase, which was approved by China Food and Drug administration in June 2011 for treating advanced NSCLC. Its approval was based on the registered Phase III trial (ICOGEN), which showed icotinib is noninferior to gefitinib. This review will discuss the role of icotinib in NSCLC, and its potential application and ongoing investigations.

Sex selection: the systematic elimination of girls.

PubMed

Oomman, Nandini; Ganatra, Bela R

2002-05-01

In strongly patriarchal societies, where the cultural and economic value of sons is at a premium, son preference manifests itself in many ways, ranging from differential allocation of household resources, medical care and neglect of girl children to female infanticide. With the increasing availability of ultrasound in the mid-1980s sex determination followed by sex-selective abortion began to become widespread as well. The following paper introduces this Roundtable and discusses the following questions: Is sex selection a part of women's right to free choice and control over their reproduction? What is the role of the medical profession? Are all manifestations of sex selection equally unethical? Are there solutions? Do the solutions themselves pose new ethical dilemmas? Following this paper, four respondents put different points of view on sex selection as a gender-based preference for a pregnancy; progress in getting the Supreme Court of India to implement a 1994 law regulating the use of antenatal diagnostic technology; why sex selection should be available as a form of reproductive choice; and why sex selection may be empowering for women and justify their actions in the short run, given the demands on them. All agree that only improved status for women and girls will reduce the demand for sex selection.

Simulating the role of visual selective attention during the development of perceptual completion

PubMed Central

Schlesinger, Matthew; Amso, Dima; Johnson, Scott P.

2014-01-01

We recently proposed a multi-channel, image-filtering model for simulating the development of visual selective attention in young infants (Schlesinger, Amso & Johnson, 2007). The model not only captures the performance of 3-month-olds on a visual search task, but also implicates two cortical regions that may play a role in the development of visual selective attention. In the current simulation study, we used the same model to simulate 3-month-olds’ performance on a second measure, the perceptual unity task. Two parameters in the model – corresponding to areas in the occipital and parietal cortices – were systematically varied while the gaze patterns produced by the model were recorded and subsequently analyzed. Three key findings emerged from the simulation study. First, the model successfully replicated the performance of 3-month-olds on the unity perception task. Second, the model also helps to explain the improved performance of 2-month-olds when the size of the occluder in the unity perception task is reduced. Third, in contrast to our previous simulation results, variation in only one of the two cortical regions simulated (i.e. recurrent activity in posterior parietal cortex) resulted in a performance pattern that matched 3-month-olds. These findings provide additional support for our hypothesis that the development of perceptual completion in early infancy is promoted by progressive improvements in visual selective attention and oculomotor skill. PMID:23106728

Simulating the role of visual selective attention during the development of perceptual completion.

PubMed

Schlesinger, Matthew; Amso, Dima; Johnson, Scott P

2012-11-01

We recently proposed a multi-channel, image-filtering model for simulating the development of visual selective attention in young infants (Schlesinger, Amso & Johnson, 2007). The model not only captures the performance of 3-month-olds on a visual search task, but also implicates two cortical regions that may play a role in the development of visual selective attention. In the current simulation study, we used the same model to simulate 3-month-olds' performance on a second measure, the perceptual unity task. Two parameters in the model - corresponding to areas in the occipital and parietal cortices - were systematically varied while the gaze patterns produced by the model were recorded and subsequently analyzed. Three key findings emerged from the simulation study. First, the model successfully replicated the performance of 3-month-olds on the unity perception task. Second, the model also helps to explain the improved performance of 2-month-olds when the size of the occluder in the unity perception task is reduced. Third, in contrast to our previous simulation results, variation in only one of the two cortical regions simulated (i.e. recurrent activity in posterior parietal cortex) resulted in a performance pattern that matched 3-month-olds. These findings provide additional support for our hypothesis that the development of perceptual completion in early infancy is promoted by progressive improvements in visual selective attention and oculomotor skill. © 2012 Blackwell Publishing Ltd.

Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity.

PubMed

Stewart, Alesha C; Bethel, Christopher R; VanPelt, Jamie; Bergstrom, Alex; Cheng, Zishuo; Miller, Callie G; Williams, Cameron; Poth, Robert; Morris, Matthew; Lahey, Olivia; Nix, Jay C; Tierney, David L; Page, Richard C; Crowder, Michael W; Bonomo, Robert A; Fast, Walter

2017-12-08

Use and misuse of antibiotics have driven the evolution of serine β-lactamases to better recognize new generations of β-lactam drugs, but the selective pressures driving evolution of metallo-β-lactamases are less clear. Here, we present evidence that New Delhi metallo-β-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites. Each of the clinical variants is shown to be progressively more thermostable and to bind zinc(II) more tightly than NDM-1, but a selective enhancement of penam turnover at low zinc(II) concentrations indicates that most of the improvement derives from catalysis rather than stability. X-ray crystallography of NDM-4 and NDM-12, as well as bioinorganic spectroscopy of dizinc(II), zinc(II)/cobalt(II), and dicobalt(II) metalloforms probe the mechanism of enhanced resistance and reveal perturbations of the dinuclear metal cluster that underlie improved catalysis. These studies support the proposal that zinc(II) scarcity, rather than changes in antibiotic structure, is driving the evolution of new NDM variants in clinical settings.

Perspectives for artificial insemination and genomics to improve global swine populations.

PubMed

Gerrits, Roger J; Lunney, Joan K; Johnson, Lawrence A; Pursel, Vernon G; Kraeling, Robert R; Rohrer, Gary A; Dobrinsky, John R

2005-01-15

Civilizations throughout the world continue to depend on pig meat as an important food source. Approximately 40% of the red meat consumed annually worldwide (94 million metric tons) is pig meat. Pig numbers (940 million) and consumption have increased consistent with the increasing world population (FAO 2002). In the past 50 years, research guided genetic selection and nutrition programs have had a major impact on improving carcass composition and efficiency of production in swine. The use of artificial insemination (AI) in Europe has also had a major impact on pig improvement in the past 35 years and more recently in the USA. Several scientific advances in gamete physiology and/or manipulation have been successfully utilized while others are just beginning to be applied at the production level. Semen extenders that permit the use of fresh semen for more than 5 days post-collection are largely responsible for the success of AI in pigs worldwide. Transfer of the best genetics has been enabled by use of AI with fresh semen, and to some extent, by use of AI with frozen semen over the past 25 years. Sexed semen, now a reality, has the potential for increasing the rate of genetic progress in AI programs when used in conjunction with newly developed low sperm number insemination technology. Embryo cryopreservation provides opportunities for international transport of maternal germplasm worldwide; non-surgical transfer of viable embryos in practice is nearing reality. While production of transgenic animals has been successful, the low level of efficiency in producing these animals and lack of information on multigene interactions limit the use of the technology in applied production systems. Technologies based on research in functional genomics, proteomics and cloning have significant potential, but considerable research effort will be required before they can be utilized for AI in pig production. In the past 15 years, there has been a coordinated worldwide scientific effort to develop the genetic linkage map of the pig with the goal of identifying pigs with genetic alleles that result in improved growth rate, carcass quality, and reproductive performance. Molecular genetic tests have been developed to select pigs with improved traits such as removal of the porcine stress (RYR1) syndrome, and selection for specific estrogen receptor (ESR) alleles. Less progress has been made in developing routine tests related to diseases. Major research in genomics is being pursued to improve the efficiency of selection for healthier pigs with disease resistance properties. The sequencing of the genome of the pig to identify new genes and unique regulatory elements holds great promise to provide new information that can be used in pig production. AI, in vitro embryo production and embryo transfer will be the preferred means of implementing these new technologies to enhance efficiency of pig production in the future.

Heterogeneity-based, multiple mechanisms in the resistance to osimertinib (AZD9291): A case report.

PubMed

Liu, Yutao; Hao, Xuezhi; Hu, Xingsheng; Li, Junling; Wang, Yan; Wang, Hongyu; Xing, Puyuan; Li, Weihua; Ying, Jianming; Han, Xiaohong; Shi, Yuankai

2018-04-01

Osimertinib is a novel, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR-mutated lung adenocarcinoma who, after 23-month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c-Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism. Our findings revealed the underlying multiple and heterogeneous mechanisms in resistance to osimertinib, suggesting combination strategies should be considered post-osimertinib progression. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

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.

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... responding to the Phase 2 synopsis, and NASA will provide that source to all the material furnished to the... to and including the date upon which Phase 2 proposals are requested. Any such changes in evaluation... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

2017-04-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. We used standard searches to find publications using ADNI data. (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design. Copyright © 2017. Published by Elsevier Inc.

Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma.

PubMed

Patel, Rutveej; Bock, Megan; Polotti, Charles F; Elsamra, Sammy

2017-02-01

Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression. Phase I trials confirmed antitumor activity of atezolizumab in patients with advanced or metastatic urothelial carcinoma. Phase II trials showed an improved response rate and a longer durable response than current conventional therapy. Phase III trials are currently underway with an estimated accrual end date of 2017. Expert opinion: MIBC is a high-risk disease, and after progression on current chemotherapy regimens, second-line treatments leave much to be desired. Emerging evidence of efficacy and safety and a recent accelerated approval by the FDA presents atezolizumab as a promising treatment option. Current clinical challenges include the details of disease progression and determining where immune checkpoint inhibition will reside in the treatment algorithm.

Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

PubMed Central

Thole, Theresa M; Lodrini, Marco; Fabian, Johannes; Wuenschel, Jasmin; Pfeil, Sebastian; Hielscher, Thomas; Kopp-Schneider, Annette; Heinicke, Ulrike; Fulda, Simone; Witt, Olaf; Eggert, Angelika; Fischer, Matthias; Deubzer, Hedwig E

2017-01-01

The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas significantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identified a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicate a significant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target. PMID:28252645

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease

PubMed Central

Beltran, William A.; Cideciyan, Artur V.; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S.; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

2015-01-01

Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

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

Research and development of methods and tools for achieving and maintaining consensus processes in the face of change within and among government oversight agencies. Progress report, October 1, 1992--March 31, 1994, Volume I

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

Not Available

1994-06-01

This progress report summarizes our research activities under our consensus grant. In year five, we devoted much of our activities to completing fundamental research projects delayed because of the considerably stepped-up effort in consensus processes efforts during development of DOE`s Five Year Waste Plan (FYWP). Following our work on various procedures for bringing together groups such as the State and Tribal Government Working Group and the Stakeholders` Forum (both of which provide input to the Five Year Waste Plan), we compiled a literature overview of small-group consensus gaining and a handbook for consensus decision making. We also tested the effectivenessmore » Of group decision support software, and designed a structured observation process and its related hard- and software. We completed studies on experts and the role of personality characteristics in consensus group influence. Results of these studies are included in this final report. In consensus processes research, we were unable to continue studying consensus groups in action. However, we did study ways to improve ways to improve DOE`s technological information exchange effectiveness. We also studied how a new administration identifies what its strategic mission is and how it gets support from existing EM managers. We identified selection criteria for locating the EM exhibit, and tested our audience selection model. We also further calibrated our consensus measure. Additional conference papers and papers for journal submission were completed during year five.« less

Country clustering applied to the water & sanitation sector: a new tool with potential applications in research & policy

PubMed Central

Onda, Kyle; Crocker, Jonny; Kayser, Georgia Lyn; Bartram, Jamie

2013-01-01

The fields of global health and international development commonly cluster countries by geography and income to target resources and describe progress. For any given sector of interest, a range of relevant indicators can serve as a more appropriate basis for classification. We create a new typology of country clusters specific to the water and sanitation (WatSan) sector based on similarities across multiple WatSan-related indicators. After a literature review and consultation with experts in the WatSan sector, nine indicators were selected. Indicator selection was based on relevance to and suggested influence on national water and sanitation service delivery, and to maximize data availability across as many countries as possible. A hierarchical clustering method and a gap statistic analysis were used to group countries into a natural number of relevant clusters. Two stages of clustering resulted in five clusters, representing 156 countries or 6.75 billion people. The five clusters were not well explained by income or geography, and were unique from existing country clusters used in international development. Analysis of these five clusters revealed that they were more compact and well separated than United Nations and World Bank country clusters. This analysis and resulting country typology suggest that previous geography- or income-based country groupings can be improved upon for applications in the WatSan sector by utilizing globally available WatSan-related indicators. Potential applications include guiding and discussing research, informing policy, improving resource targeting, describing sector progress, and identifying critical knowledge gaps in the WatSan sector. PMID:24054545

Progress and challenges in improving the nutritional quality of rice (Oryza sativa L.).

PubMed

Birla, Deep Shikha; Malik, Kapil; Sainger, Manish; Chaudhary, Darshna; Jaiwal, Ranjana; Jaiwal, Pawan K

2017-07-24

Rice is a staple food for more than 3 billion people in more than 100 countries of the world but ironically it is deficient in many bioavailable vitamins, minerals, essential amino- and fatty-acids and phytochemicals that prevent chronic diseases like type 2 diabetes, heart disease, cancers, and obesity. To enhance the nutritional and other quality aspects of rice, a better understanding of the regulation of the processes involved in the synthesis, uptake, transport, and metabolism of macro-(starch, seed storage protein and lipid) and micronutrients (vitamins, minerals and phytochemicals) is required. With the publication of high quality genomic sequence of rice, significant progress has been made in identification, isolation, and characterization of novel genes and their regulation for the nutritional and quality enhancement of rice. During the last decade, numerous efforts have been made to refine the nutritional and other quality traits either by using the traditional breeding with high through put technologies such as marker assisted selection and breeding, or by adopting the transgenic approach. A significant improvement in vitamins (A, folate, and E), mineral (iron), essential amino acid (lysine), and flavonoids levels has been achieved in the edible part of rice, i.e., endosperm (biofortification) to meet the daily dietary allowance. However, studies on bioavailability and allergenicity on biofortified rice are still required. Despite the numerous efforts, the commercialization of biofortified rice has not yet been achieved. The present review summarizes the progress and challenges of genetic engineering and/or metabolic engineering technologies to improve rice grain quality, and presents the future prospects in developing nutrient dense rice to save the everincreasing population, that depends solely on rice as the staple food, from widespread nutritional deficiencies.

Diagnostic and Prognostic Value of the Combination of Two Measures of Verbal Memory in Mild Cognitive Impairment due to Alzheimer's Disease.

PubMed

Sala, Isabel; Illán-Gala, Ignacio; Alcolea, Daniel; Sánchez-Saudinós, Ma Belén; Salgado, Sergio Andrés; Morenas-Rodríguez, Estrella; Subirana, Andrea; Videla, Laura; Clarimón, Jordi; Carmona-Iragui, María; Ribosa-Nogué, Roser; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

2017-01-01

Episodic memory impairment is the core feature of typical Alzheimer's disease. To evaluate the performance of two commonly used verbal memory tests to detect mild cognitive impairment due to Alzheimer's disease (MCI-AD) and to predict progression to Alzheimer's disease dementia (AD-d). Prospective study of MCI patients in a tertiary memory disorder unit. Patients underwent an extensive neuropsychological battery including two tests of declarative verbal memory: The Free and Cued Selective Reminding Test (FCSRT) and the word list learning task from the Consortium to Establish a Registry for Alzheimer's disease (CERAD-WL). Cerebrospinal fluid (CSF) was obtained from all patients and MCI-AD was defined by means of the t-Tau/Aβ1-42 ratio. Logistic regression analyses tested whether the combination of FCSRT and CERAD-WL measures significantly improved the prediction of MCI-AD. Progression to AD-d was analyzed in a Cox regression model. A total of 202 MCI patients with a mean follow-up of 34.2±24.2 months were included and 98 (48.5%) met the criteria for MCI-AD. The combination of FCSRT and CERAD-WL measures improved MCI-AD classification accuracy based on CSF biomarkers. Both tests yielded similar global predictive values (59.9-65.3% and 59.4-62.8% for FCSRT and CERAD-WL, respectively). MCI-AD patients with deficits in both FCSRT and CERAD-WL had a faster progression to AD-d than patients with deficits in only one test. The combination of FCSRT and CERAD-WL improves the classification of MCI-AD and defines different prognostic profiles. These findings have important implications for clinical practice and the design of clinical trials.

Do recommendations for institutional food service result in better food service? A study of compliance in Danish hospitals and nursing homes from 1995 to 2002-2003.

PubMed

Mikkelsen, B E; Beck, A M; Lassen, A

2007-01-01

Since 1995, significant efforts by authorities and researchers have been directed towards addressing the nutritional problems in Danish hospitals and nursing homes. The purpose of this study was to investigate whether the increased focus on nutritional problems in patients and nursing home residents has resulted in measurable progress. A questionnaire-based study was carried out among foodservice managers in Danish hospitals (n=96) and nursing homes (n=898) in 1995 and 2002/3 (n=90) and (n=682), respectively. The study used compliance with selected issues in the official Danish recommendations for institutional food service as an indicator for progress. The issues included: using nutrient calculated recipes/menus, offering menu choice options, using feedback routines on acceptability of menus, maintaining nutritional steering committees, employing food and nutrition contact persons, employing official recommendations and offering choice between three different menu energy levels. Hospitals had a higher compliance compared to nursing homes. In 1995, this was the case for all questions asked and differences were statistically significant. Also in 2002/3, hospitals had a higher compliance, except in the case of established feedback routines. Differences were statistically significant. The results indicate that nutritional care is higher on the agenda in hospital, than in nursing homes. However, very little progress can be seen in compliance when results are analysed over the 8-year period. The only progress for nursing homes was that more homes had implemented feedback routines on acceptability of food service in 2002/3 than in 1995. The difference was statistically significant. For hospitals, however, no progress was found between 1995 and 2002/3. The attempts to improve the nutritional status of hospital patients and nursing home residents seem to have failed. Still, the initiatives taken to improve the situation seem relevant. Especially the nursing homes might benefit from advantage of these experiences.

Successful treatment with denosumab in a patient with sacral giant cell tumor of bone refractory to combination therapy with arterial embolization and zoledronic acid: A case report

PubMed Central

Nishimura, Shunji; Hashimoto, Kazuhiko; Tan, Akihiro; Yagyu, Yukinobu; Akagi, Masao

2017-01-01

Giant cell tumor of bone (GCTB) is commonly treated with surgery; however, surgery of GCTB in the sacrum may be challenging due to the associated risk. A conservative approach may be selective arterial embolization or zoledronic acid (ZOL) treatment; however, there are currently no studies investigating the efficacy of combining these two treatments. Denosumab may also be used; however, to the best of our knowledge, there are no reports of a stepwise approach for the use of all three treatments in a single patient. We herein present such a case. A 32-year-old woman diagnosed with sacral GCTB was treated with selective arterial embolization for 3 months. No improvement was observed, and monthly infusions of ZOL were added (administered 2 weeks after each arterial embolization treatment). Ten months after the initiation of ZOL, there was still no improvement. The therapy was changed to denosumab 120 mg, injected subcutaneously once a month. By the third dose, the buttock pain had decreased and the patient became ambulatory. At 5 and 10 months, computed tomography scans revealed bone sclerosis gradually appearing around the sacrum. By 1 year, needle biopsy detected no neoplastic cells. At that point, the patient discontinued treatment, as there was hepatic function impairment due to a history of hepatitis B. Despite treatment discontinuation, the patient exhibited no further symptoms, there were no signs of progression on radiography, and surgery was not required. Our patient experienced treatment failure with selective arterial embolization. The combination of ZOL with selective arterial embolization also did not improve the patient's condition. Denosumab was found to be superior to both treatments, achieving tumor remission. The patient remains symptom- and disease-free. Further studies are required, but our results suggest that patients with unresectable GCTB who fail to respond to selective arterial embolization may benefit from denosumab treatment, but not from combination therapy with selective arterial embolization and ZOL. PMID:28451403

Recent progress in low-voltage cathodoluminescent materials: synthesis, improvement and emission properties.

PubMed

Li, Guogang; Lin, Jun

2014-01-01

Nowadays there are several technologies used for flat panel displays (FPDs) and the development of FPDs with enhanced energy efficiency and improved display quality is strongly required. Field emission displays (FEDs) have been considered as one of the most promising next generation flat panel display technologies due to their excellent display performance and low energy consumption. For the development of FEDs, phosphors are irreplaceable components. In the past decade, the study of highly efficient low-voltage cathodoluminescent materials, namely FED phosphors, has become the focus of enhancing energy efficiency and realizing high-quality displays. This review summaries the recent progress in the chemical synthesis and improvement of novel, rare-earth and transition metal ions activated inorganic cathodoluminescent materials in powder and thin film forms. The discussion is focused on the modification of morphology, size, surface, composition and conductivity of phosphors and the corresponding effects on their cathodoluminescent properties. Special emphases are given to the selection of host and luminescent centers, the adjustment of emission colors through doping concentration optimization, energy transfer and mono- or co-doping activator ions, the improvement of chromaticity, color stability and color gamut as well as the saturation behavior and the degradation behavior of phosphors under the excitation of a low-voltage electron beam. Finally, the research prospects and future directions of FED phosphors are discussed with recommendations to facilitate the further study of new and highly efficient low-voltage cathodoluminescent materials.

Can we maximize both value and quality in gynecologic cancer care? A work in progress.

PubMed

Havrilesky, Laura J; Fountain, Cynthia

2014-01-01

Value is defined as desirable health outcomes achieved per monetary unit spent. Comparative effectiveness research and cost-effectiveness research are methods that have been developed to quantify effectiveness and value to inform management decisions. In this article we review the comparative and cost-effectiveness literature in the field of ovarian cancer treatment. Studies have shown that improved ovarian cancer survival is associated with complete primary surgical cytoreduction, with treatment at high volume facilities by subspecialist providers (gynecologic oncologists) and with National Comprehensive Cancer Network (NCCN) guideline-adherent care in both surgical staging and chemotherapy regimens. Intraperitoneal/intravenous chemotherapy (compared with intravenous alone) has been associated with improved survival and cost-effectiveness. Bevacizumab for primary and maintenance therapy has been found to not be cost-effective (even in selective subsets) despite a small progression-free survival (PFS) advantage. For platinum-sensitive recurrent ovarian cancer, secondary cytoreduction and platinum-based combinations are associated with improved overall survival (OS); several platinum-based combinations have also been found cost-effective. For platinum-resistant recurrence, single agent therapy and supportive care are cost-effective compared with combination therapies. Although little prospective clinical research has been done around end-of-life care, one study reported that for platinum-resistant ovarian cancer, palliative intervention would potentially reduce costs and increase quality adjusted life years compared with usual care (based on improvement in quality of life [QOL]). Overall, cost comparisons of individual chemotherapy regimens are highly dependent on market prices of novel therapeutic agents.

Using dreams to assess clinical change during treatment.

PubMed

Glucksman, Myron L; Kramer, Milton

2004-01-01

This article describes several studies that examine the relationship between the manifest content of selected dreams reported by patients and their clinical progress during psychoanalytic and psychodynamically oriented treatment. There are a number of elements that dreaming and psychotherapy have in common: affect regulation; conflict resolution; problem-solving; self-awareness; mastery and adaptation. Four different studies examined the relationship between the manifest content of selected dreams and clinical progress during treatment. In each study, the ratings of manifest content and clinical progress by independent observers were rank-ordered and compared. In three of the four studies there was a significant correlation between the rankings of manifest content and the rankings of clinical progress. This finding suggests that the manifest content of dreams can be used as an independent variable to assess clinical progress during psychoanalytic and psychodynamically oriented treatment.

Alternative RNA splicing of the MEAF6 gene facilitates neuroendocrine prostate cancer progression.

PubMed

Lee, Ahn R; Li, Yinan; Xie, Ning; Gleave, Martin E; Cox, Michael E; Collins, Colin C; Dong, Xuesen

2017-04-25

Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers. We show that MEAF6-1 splicing is stimulated by neuronal RNA splicing factor SRRM4. Rather than inducing neuroendocrine trans-differentiation of cells in prostate adenocarcinoma, MEAF6-1 upregulation stimulates cell proliferation, anchorage-independent cell growth, invasion and xenograft tumor growth. Gene microarray identifies that these MEAF6-1 actions are in part mediated by the ID1 and ID3 genes. These findings suggest that the MEAF6-1 variant does not induce neuroendocrine differentiation of prostate cancer cells, but rather facilitates t-NEPC progression by increasing the proliferation rate of cells that have acquired neuroendocrine phenotypes.

The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases.

PubMed

Vellayappan, Balamurugan A; Chao, Samuel T; Foote, Matthew; Guckenberger, Matthias; Redmond, Kristin J; Chang, Eric L; Mayr, Nina A; Sahgal, Arjun; Lo, Simon S

2018-06-25

Owing to improvements in clinical care and systemic therapy, more patients are being diagnosed with, and living longer with, spinal metastases (SM). In parallel, tremendous technological progress has been made in the field of radiation oncology. Advances in both software and hardware are able to integrate three- (and four-) dimensional body imaging with spatially accurate treatment delivery methods. This is able to improve the efficacy, shorten the overall treatment schedule and potentially reduce treatment-related toxicity. Areas covered: In this review, we will look at the progress made by stereotactic body radiotherapy (SBRT) in the management of SM. We will review the technological factors which have enabled the widespread use of SBRT. The efficacy of SBRT, in various clinical scenarios, and associated toxicities will be reviewed. Lastly, we will discuss about patient selection, and provide a five-year roadmap. Expert commentary: Spine SBRT is a safe and efficacious treatment option. Practice guidelines recommend the use of SBRT in oligo-metastatic patients especially those with radio-resistant cancer types, and in scenarios involving re-irradiation. SBRT offers patients dose-intensification over a short schedule which may allow less time off systemic therapy. The results of the phase III trials are eagerly awaited.

Potential crashworthiness benefits to general aviation from Indianapolis Motor Speedway technology.

PubMed

Jennings, R T; Mohler, S R

1988-01-01

General aviation crashworthiness can potentially benefit from certain advances being accomplished by the automobile industry. Progressive improvements in crash protection technology, as documented by a dramatic reduction in crash injuries and fatalities at the Indianapolis Motor Speedway, reflect improved crashworthiness. The speeds of survivable general aviation aircraft impacts are in the range of the Indianapolis Motor Speedway crashes (200-220 mph). This paper relates the declining crash death rates at Indy by decade versus the increase in speeds. The continuous rise in speeds has prompted the development of new crashworthy designs and driver protection equipment. Crashworthiness improvements include crushable surrounding structures, high-grade restraint systems, protective head gear, fire resistant clothing, break-away structural components, and a "protective cocoon" concept. Adaptation of selected advances in crashworthiness design and operations accomplished at the Indianapolis Motor Speedway to the next generation of general aviation aircraft should provide significant dividends in survival of air crashes.

Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization

PubMed Central

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-01-01

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we described the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC50 values with selectivity for B-RafV600E in vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells. PMID:22875039

Development of a novel class of B-Raf(V600E)-selective inhibitors through virtual screening and hierarchical hit optimization.

PubMed

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-09-28

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E) mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-Raf(V600E) selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC(50) values were identified as B-Raf(V600E) inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC(50) values with selectivity for B-Raf(V600E)in vitro and exclusive cytotoxicity against B-Raf(V600E) harboring cancer cells.

Evaluating barnyard Best Management Practices in Wisconsin using upstream-downstream monitoring

USGS Publications Warehouse

Stuntebeck, Todd D.

1995-01-01

The Nonpoint Source Water Pollution Abatement Program was created in 1978 by the Wisconsin Legislature. The goal of the program is to improve and protect the water quality of lakes, streams, wetlands, and ground water within selected priority watersheds by controlling sources of nonpoint pollution. For each selected watershed, the Wisconsin Department of Natural Resources drafts a management plan that guides the implementation of pollution-control strategies known as Best Management Practices (BMP's). This plan summarizes resource and land-use inventories, describes the results of pollution-source modeling, and suggests pollution reduction goals. The U.S. Geological Survey, through a cooperative effort with the Wisconsin Department of Natural Resources, is monitoring water-quality improvements that result from the implementation of BMP's. The data collected are then compared to the watershed plans to assess progress and determine whether goals are being realized. This fact sheet describes the data-collection efforts, preliminary results, and planned data-analysis techniques of monitoring projects for pre-BMP conditions at two barnyards, one each on Otter Creek and Halfway Prairie Creek.

Will the 'principles of effectiveness' improve prevention practice? Early findings from a diffusion study.

PubMed

Hallfors, D; Godette, D

2002-08-01

This study examines adoption and implementation of the US Department of Education's new policy, the 'Principles of Effectiveness', from a diffusion of innovations theoretical framework. In this report, we evaluate adoption in relation to Principle 3: the requirement to select research-based programs. Results from a sample of 104 school districts in 12 states indicate that many districts appear to be selecting research-based curricula, but that the quality of implementation is low. Only 19% of the responding district coordinators indicated that schools were implementing a research-based curriculum with fidelity. Common problems included lack of teacher training, lack of requisite materials, use of some but not all of the required lessons and teaching strategies, and failure to deliver lessons to age-appropriate student groups. This study represents the first attempt to assess the quality of implementation of research-based programs as required by the Principles of Effectiveness. We conclude that low levels of funding, inadequate infrastructure, decentralized decision making and lack of program guidance have contributed to the slow progress in improving school-based prevention.

Frontline treatment of acute myeloid leukemia in adults

PubMed Central

Tamamyan, Gevorg; Kadia, Tapan; Ravandi, Farhad; Borthakur, Gautam; Cortes, Jorge; Jabbour, Elias; Daver, Naval; Ohanian, Maro; Kantarjian, Hagop; Konopleva, Marina

2017-01-01

Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients’ age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40–50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30–40% up to 80–90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the “7+3” regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the “7+3” regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future. PMID:28109402

Australasian nutrition research for prevention and management of child obesity: innovation and progress in the last decade.

PubMed

Golley, R K; McNaughton, S A; Collins, C E; Magarey, A; Garnett, S P; Campbell, K J; Mallan, K; Burrows, T

2014-12-01

The Food and Nutrition stream of Australasian Child and Adolescent Obesity Research Network (ACAORN) aims to improve the quality of dietary methodologies and the reporting of dietary intake within Australasian child obesity research (http://www.acaorn.org.au/streams/nutrition/). With 2012 marking ACAORN's 10th anniversary, this commentary profiles a selection of child obesity nutrition research published over the last decade by Food and Nutrition Stream members. In addition, stream activities have included the development of an online selection guide to assist researchers in their selection of appropriate dietary intake methodologies (http://www.acaorn.org.au/streams/nutrition/dietary-intake/index.php). The quantity and quality of research to guide effective child obesity prevention and treatment has increased substantially over the last decade. ACAORN provides a successful case study of how research networks can provide a collegial atmosphere to foster and coordinate research efforts in an otherwise competitive environment. © 2014 The Authors. Pediatric Obesity © 2014 International Association for the Study of Obesity.

Looking forward in geriatric anxiety and depression: implications of basic science for the future.

PubMed

Gershenfeld, Howard K; Philibert, Robert A; Boehm, Gary W

2005-12-01

Major depression and anxiety are common psychiatric illnesses whose etiology remains incompletely understood. This review highlights progress in understanding the etiology of these illnesses through genetic strategies and looks forward to their impact on geriatric psychiatry. We briefly address three broad domains of progress, namely 1) genetic approaches to etiology, including linkage and association studies, pharmacogenetics ("personalized medicine"), and gene x environment interactions; 2) mechanisms of thyroid and testosterone action via nuclear receptors, given these hormones' status as possible augmenters of antidepressants; and 3) the role of the neuroimmune system as a contributor to the stress response. Genetic strategies offer one path for converting correlational findings into causal pathways while complementing studies of a gene's function at the molecular, cellular, network, and whole-organismal levels. Neuroendocrine supplementation (thyroid and testosterone) has a long history and tradition. A molecular understanding of nuclear receptor pathways and their coactivators, the mediator complex proteins, provides a rationale for improved targeting of hormonal action in a tissue-selective manner, yielding drugs with improved safety and efficacy. Neural-immune interactions in psychiatric illness remain tantalizing topics. Research suggests that cytokine pathways may contribute to the maintenance or susceptibility to stress, anxiety, and depressive disorders. The reciprocal and recursive interactions among basic science, drug discovery, and clinical science will continue to provide hopeful themes for improving the lives of patients with treatment-refractive psychiatric illness.

Paralympic Sprint Performance Between 1992 and 2012.

PubMed

Grobler, Lara; Ferreira, Suzanne; Terblanche, Elmarie

2015-11-01

The Paralympic Games have undergone many changes since their inception in 1960, one being the advances made in running-specific prostheses (RSPs) for track athletes with lower-limb amputations. To investigate the sprinting-performance changes in athletes with lower-limb amputations since 1992 to assess whether the influence of developments in RSP technology is evident. The results of the Olympic and Paralympic Games ranging between 1992 and 2012 for the 100-m and 200-m were collected, and performance trends, percentage change in performance, and competition density (CD) were calculated. The results indicate that the greatest performance increases were seen in athletes with lower-limb amputations (T42 = 26%, T44 = 14%). These performance improvements were greater than for Olympic athletes (<3%), as well as Paralympic athletes from other selected classes (<10%). The T42 and T44 classes also showed the lowest CD values. These results suggest that although there is an overall trend for improved Paralympic sprint performances, RSP technology has played a noteworthy role in the progression of performances of athletes with amputations. It is also hypothesized that the difference in the performance improvements between the T42 and T44 classes is due to the level of disability and therefore the extent to which technology is required to enable locomotion. It is evident that RSP technology has played a significant role in the progression of performances in athletes with lower-limb amputations.

RTEMS CENTRE- RTEMS Improvement

NASA Astrophysics Data System (ADS)

Silva, Helder; Constantino, Alexandre; Freitas, Daniel; Coutinho, Manuel; Faustino, Sergio; Sousa, Jose; Dias, Luis; Zulianello, Marco

2010-08-01

During the last two years, EDISOFT's RTEMS CENTRE team [1], jointly with the European Space Agency and with the support of the worldwide RTEMS community [2], have been developing an activity to facilitate the qualification of the real-time operating system RTEMS (Real-Time Operating System for Multiprocessor Systems). This paper intends to give a high level visibility of the progress and the results obtained in the RTEMS Improvement [3] activity. The primary objective [4] of the project is to improve the RTEMS product, its documentation and to facilitate the qualification of RTEMS for future space missions, taking into consideration the specific operational requirements. The sections below provide a brief overview of the RTEMS operating system and the activities performed in the RTEMS Improvement project, which includes the selection of API managers to be qualified, the tailoring process, the requirements analysis, the reverse engineering and design of the RTEMS, the quality assurance process, the ISVV activities, the test campaign, the results obtained, the criticality analysis and the facilitation of qualification process.

A 100-Year Review: Methods and impact of genetic selection in dairy cattle-From daughter-dam comparisons to deep learning algorithms.

PubMed

Weigel, K A; VanRaden, P M; Norman, H D; Grosu, H

2017-12-01

In the early 1900s, breed society herdbooks had been established and milk-recording programs were in their infancy. Farmers wanted to improve the productivity of their cattle, but the foundations of population genetics, quantitative genetics, and animal breeding had not been laid. Early animal breeders struggled to identify genetically superior families using performance records that were influenced by local environmental conditions and herd-specific management practices. Daughter-dam comparisons were used for more than 30 yr and, although genetic progress was minimal, the attention given to performance recording, genetic theory, and statistical methods paid off in future years. Contemporary (herdmate) comparison methods allowed more accurate accounting for environmental factors and genetic progress began to accelerate when these methods were coupled with artificial insemination and progeny testing. Advances in computing facilitated the implementation of mixed linear models that used pedigree and performance data optimally and enabled accurate selection decisions. Sequencing of the bovine genome led to a revolution in dairy cattle breeding, and the pace of scientific discovery and genetic progress accelerated rapidly. Pedigree-based models have given way to whole-genome prediction, and Bayesian regression models and machine learning algorithms have joined mixed linear models in the toolbox of modern animal breeders. Future developments will likely include elucidation of the mechanisms of genetic inheritance and epigenetic modification in key biological pathways, and genomic data will be used with data from on-farm sensors to facilitate precision management on modern dairy farms. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

PubMed

Epperly, Ted; Dunay, Megan A; Boice, Jack L

2017-06-15

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

Microbial biocatalyst developments to upgrade fossil fuels.

PubMed

Kilbane, John J

2006-06-01

Steady increases in the average sulfur content of petroleum and stricter environmental regulations concerning the sulfur content have promoted studies of bioprocessing to upgrade fossil fuels. Bioprocesses can potentially provide a solution to the need for improved and expanded fuel upgrading worldwide, because bioprocesses for fuel upgrading do not require hydrogen and produce far less carbon dioxide than thermochemical processes. Recent advances have demonstrated that biodesulfurization is capable of removing sulfur from hydrotreated diesel to yield a product with an ultra-low sulfur concentration that meets current environmental regulations. However, the technology has not yet progressed beyond laboratory-scale testing, as more efficient biocatalysts are needed. Genetic studies to obtain improved biocatalysts for the selective removal of sulfur and nitrogen from petroleum provide the focus of current research efforts.

Polycrystalline Diamond Coating of Additively Manufactured Titanium for Biomedical Applications.

PubMed

Rifai, Aaqil; Tran, Nhiem; Lau, Desmond W; Elbourne, Aaron; Zhan, Hualin; Stacey, Alastair D; Mayes, Edwin L H; Sarker, Avik; Ivanova, Elena P; Crawford, Russell J; Tran, Phong A; Gibson, Brant C; Greentree, Andrew D; Pirogova, Elena; Fox, Kate

2018-03-14

Additive manufacturing using selective laser melted titanium (SLM-Ti) is used to create bespoke items across many diverse fields such as medicine, defense, and aerospace. Despite great progress in orthopedic implant applications, such as for "just in time" implants, significant challenges remain with regards to material osseointegration and the susceptibility to bacterial colonization on the implant. Here, we show that polycrystalline diamond coatings on these titanium samples can enhance biological scaffold interaction improving medical implant applicability. The highly conformable coating exhibited excellent bonding to the substrate. Relative to uncoated SLM-Ti, the diamond coated samples showed enhanced mammalian cell growth, enriched apatite deposition, and reduced microbial S. aureus activity. These results open new opportunities for novel coatings on SLM-Ti devices in general and especially show promise for improved biomedical implants.

Nanostructured Electrocatalysts for PEM Fuel Cells and Redox Flow Batteries: A Selected Review

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

Shao, Yuyan; Cheng, Yingwen; Duan, Wentao

2015-12-04

PEM fuel cells and redox flow batteries are two very similar technologies which share common component materials and device design. Electrocatalysts are the key components in these two devices. In this Review, we discuss recent progress of electrocatalytic materials for these two technologies with a focus on our research activities at Pacific Northwest National Laboratory (PNNL) in the past years. This includes (1) nondestructive functionalization of graphitic carbon as Pt support to improve its electrocatalytic performance, (2) triple-junction of metal–carbon–metal oxides to promote Pt performance, (3) nitrogen-doped carbon and metal-doped carbon (i.e., metal oxides) to improve redox reactions in flowmore » batteries. A perspective on future research and the synergy between the two technologies are also discussed.« less

Representation of the Auroral and Polar Ionosphere in the International Reference Ionosphere (IRI)

NASA Technical Reports Server (NTRS)

Bilitza, Dieter; Reinisch, Bodo

2013-01-01

This issue of Advances in Space Research presents a selection of papers that document the progress in developing and improving the International Reference Ionosphere (IRI), a widely used standard for the parameters that describe the Earths ionosphere. The core set of papers was presented during the 2010 General Assembly of the Committee on Space Research in Bremen, Germany in a session that focused on the representation of the auroral and polar ionosphere in the IRI model. In addition, papers were solicited and submitted from the scientific community in a general call for appropriate papers.

Surgical treatment in combined hamartoma of the retina and retinal pigment epithelium.

PubMed

Sánchez-Vicente, J L; Rueda-Rueda, T; Llerena-Manzorro, L; Molina-Socola, F E; Contreras-Díaz, M; Szewc, M; Vital-Berral, C; Alfaro-Juárez, A; Medina-Tapia, A; López-Herrero, F; González-García, L; Muñoz-Morales, A

2017-03-01

The case is presented of a 39 year-old man with a combined hamartoma of the retina and retinal pigment epithelium, who experienced progressive visual loss and worsening of metamorphopsia. The patient underwent vitrectomy and epiretinal component peeling, with improvement in visual acuity, metamorphopsia, and retinal architecture, assessed by optical coherence tomography. Selected patients with combined hamartomas of the retina and retinal pigment epithelium may benefit from surgical management. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States: A Registry Report.

PubMed

Gruessner, Angelika C; Gruessner, Rainer W G

2018-06-01

Successful pancreas transplantation is still the only method to restore short-term and long-term insulin independence and good metabolic control for patients with diabetes. Since the first transplant in 1966, tremendous progress in outcome was made; however, transplant numbers have declined since 2004. This article describes the development and risk factors of pancreas transplantation with or without a kidney graft between 2001 and 2016. Patient survival and graft function improved significantly owing to careful recipient and donor selection, which reduced technical failure and immunologic graft loss rates. Published by Elsevier Inc.

Electrochemical and optical biosensors based on nanomaterials and nanostructures: a review.

PubMed

Li, Ming; Li, Rui; Li, Chang Ming; Wu, Nianqiang

2011-06-01

Nanomaterials and nanostructures exhibit unique size-tunable and shape-dependent physicochemical properties that are different from those of bulk materials. Advances of nanomaterials and nanostructures open a new door to develop various novel biosensors. The present work has reviewed the recent progress in electrochemical, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS) and fluorescent biosensors based on nanomaterials and nanostructures. An emphasis is put on the research that demonstrates how the performance of biosensors such as the limit of detection, sensitivity and selectivity is improved by the use of nanomaterials and nanostructures.

[Attention and aging].

PubMed

Siéroff, Eric; Piquard, Ambre

2004-12-01

Due to progress in the cognitive theories in the last twenty years, the description of attentional deficits associated with normal or pathological aging has substantially improved. In this article, attentional deficits are presented according to Posner theory, which describes three sub-systems in a global network of attention: vigilance, selective attention, command. This theory not only characterizes the functions of these subsystems, but gives precise indications about their anatomical and neurochemical substrates. Several clinical tests can be described for each of these different subsystems. The main attentional deficits are presented in the second part of this paper: if some decline of the attentional command occurs in normal aging, a real deficit in this subsystem is found in most degenerative processes (frontotemporal dementia, Alzheimer and Parkinson diseases). Alzheimer disease is also frequently associated with a deficit of selective spatial attention, early in the evolution of the disease.

Deficiencies in FY 1998 DOD Financial Statements and Progress Toward Improved Financial Reporting

DTIC Science & Technology

1999-11-26

DEFICIENCIES IN FY 1998 DOD FINANCIAL STATEMENTS AND PROGRESS TOWARD IMPROVED FINANCIAL REPORTING Report No. D-2000-041 November 26, 1999 Office... Financial Reporting (Report No. D-2000-041) We are providing this audit report for information and use. It identifies and summarizes the major...8FI-2025.02) Deficiencies in FY 1998 DoD Financial Statements and Progress Toward Improved Financial Reporting Executive Summary Introduction

Mate choice and sexual selection: What have we learned since Darwin?

PubMed Central

Jones, Adam G.; Ratterman, Nicholas L.

2009-01-01

Charles Darwin laid the foundation for all modern work on sexual selection in his seminal book The Descent of Man, and Selection in Relation to Sex. In this work, Darwin fleshed out the mechanism of sexual selection, a hypothesis that he had proposed in The Origin of Species. He went well beyond a simple description of the phenomenon by providing extensive evidence and considering the far-reaching implications of the idea. Here we consider the contributions of Darwin to sexual selection with a particular eye on how far we have progressed in the last 150 years. We focus on 2 key questions in sexual selection. First, why does mate choice evolve at all? And second, what factors determine the strength of mate choice (or intensity of sexual selection) in each sex? Darwin provided partial answers to these questions, and the progress that has been made on both of these topics since his time should be seen as one of the great triumphs of modern evolutionary biology. However, a review of the literature shows that key aspects of sexual selection are still plagued by confusion and disagreement. Many of these areas are complex and will require new theory and empirical data for complete resolution. Overall, Darwin's contributions are still surprisingly relevant to the modern study of sexual selection, so students of evolutionary biology would be well advised to revisit his works. Although we have made significant progress in some areas of sexual selection research, we still have much to accomplish. PMID:19528643

Mate choice and sexual selection: what have we learned since Darwin?

PubMed

Jones, Adam G; Ratterman, Nicholas L

2009-06-16

Charles Darwin laid the foundation for all modern work on sexual selection in his seminal book The Descent of Man, and Selection in Relation to Sex. In this work, Darwin fleshed out the mechanism of sexual selection, a hypothesis that he had proposed in The Origin of Species. He went well beyond a simple description of the phenomenon by providing extensive evidence and considering the far-reaching implications of the idea. Here we consider the contributions of Darwin to sexual selection with a particular eye on how far we have progressed in the last 150 years. We focus on 2 key questions in sexual selection. First, why does mate choice evolve at all? And second, what factors determine the strength of mate choice (or intensity of sexual selection) in each sex? Darwin provided partial answers to these questions, and the progress that has been made on both of these topics since his time should be seen as one of the great triumphs of modern evolutionary biology. However, a review of the literature shows that key aspects of sexual selection are still plagued by confusion and disagreement. Many of these areas are complex and will require new theory and empirical data for complete resolution. Overall, Darwin's contributions are still surprisingly relevant to the modern study of sexual selection, so students of evolutionary biology would be well advised to revisit his works. Although we have made significant progress in some areas of sexual selection research, we still have much to accomplish.

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

PubMed Central

Chavez-Gonzalez, Antonieta; Bakhshinejad, Babak; Pakravan, Katayoon

2018-01-01

Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID:27678246

Visual field progression in glaucoma: total versus pattern deviation analyses.

PubMed

Artes, Paul H; Nicolela, Marcelo T; LeBlanc, Raymond P; Chauhan, Balwantray C

2005-12-01

To compare visual field progression with total and pattern deviation analyses in a prospective longitudinal study of patients with glaucoma and healthy control subjects. A group of 101 patients with glaucoma (168 eyes) with early to moderately advanced visual field loss at baseline (average mean deviation [MD], -3.9 dB) and no clinical evidence of media opacity were selected from a prospective longitudinal study on visual field progression in glaucoma. Patients were examined with static automated perimetry at 6-month intervals for a median follow-up of 9 years. At each test location, change was established with event and trend analyses of total and pattern deviation. The event analyses compared each follow-up test to a baseline obtained from averaging the first two tests, and visual field progression was defined as deterioration beyond the 5th percentile of test-retest variability at three test locations, observed on three consecutive tests. The trend analyses were based on point-wise linear regression, and visual field progression was defined as statistically significant deterioration (P < 5%) worse than -1 dB/year at three locations, confirmed by independently omitting the last and the penultimate observation. The incidence and the time-to-progression were compared between total and pattern deviation analyses. To estimate the specificity of the progression analyses, identical criteria were applied to visual fields obtained in 102 healthy control subjects, and the rate of visual field improvement was established in the patients with glaucoma and the healthy control subjects. With both event and trend methods, pattern deviation analyses classified approximately 15% fewer eyes as having progressed than did the total deviation analyses. In eyes classified as progressing by both the total and pattern deviation methods, total deviation analyses tended to detect progression earlier than the pattern deviation analyses. A comparison of the changes observed in MD and the visual fields' general height (estimated by the 85th percentile of the total deviation values) confirmed that change in the glaucomatous eyes almost always comprised a diffuse component. Pattern deviation analyses of progression may therefore underestimate the true amount of glaucomatous visual field progression. Pattern deviation analyses of visual field progression may underestimate visual field progression in glaucoma, particularly when there is no clinical evidence of increasing media opacity. Clinicians should have access to both total and pattern deviation analyses to make informed decisions on visual field progression in glaucoma.

Slow progress on meeting hospital safety standards: learning from the Leapfrog Group's efforts.

PubMed

Moran, John; Scanlon, Dennis

2013-01-01

In response to the Institute of Medicine's To Err Is Human report on the prevalence of medical errors, the Leapfrog Group, an organization that promotes hospital safety and quality, established a voluntary hospital survey assessing compliance with several safety standards. Using data from the period 2002-07, we conducted the first longitudinal assessment of how hospitals in specific cities and states initially selected by Leapfrog progressed on public reporting and adoption of standards requiring the use of computerized drug order entry and hospital intensivists. Overall, little progress was observed. Reporting rates were unchanged over the study period. Adoption of computerized drug order entry increased from 2.94 percent to 8.13 percent, and intensivist staffing increased from 14.74 percent to 21.40 percent. These findings should not be viewed as an indictment of Leapfrog but may reflect various challenges. For example, hospitals faced no serious threats to their market share if purchasers shifted business away from those that either didn't report data or didn't meet the standards. In the absence of mandatory reporting, policy makers might need to act to address these challenges to ensure improvements in quality.

Selecting for Ethnically Diverse Children Who May Be Gifted Using Raven's Standard Progressive Matrices and Naglieri Nonverbal Abilities Test

ERIC Educational Resources Information Center

Lewis, Joan D.; DeCamp-Fritson, Stephanie S.; Ramage, Jean C.; McFarland, Max A.; Archwamety, Teara

2007-01-01

The purpose of this study was to compare the effectiveness of the Raven's Standard Progressive Matrices, the Naglieri Nonverbal Abilities Test (NNAT), and the Iowa Test of Basic Skills (ITBS) in selecting for ethnically diverse students who may be gifted. The participants of the study were 175 students enrolled in Grades 3-5 and Grade 8 in a…

Progressive Band Selection

NASA Technical Reports Server (NTRS)

Fisher, Kevin; Chang, Chein-I

2009-01-01

Progressive band selection (PBS) reduces spectral redundancy without significant loss of information, thereby reducing hyperspectral image data volume and processing time. Used onboard a spacecraft, it can also reduce image downlink time. PBS prioritizes an image's spectral bands according to priority scores that measure their significance to a specific application. Then it uses one of three methods to select an appropriate number of the most useful bands. Key challenges for PBS include selecting an appropriate criterion to generate band priority scores, and determining how many bands should be retained in the reduced image. The image's Virtual Dimensionality (VD), once computed, is a reasonable estimate of the latter. We describe the major design details of PBS and test PBS in a land classification experiment.

Children’s belief- and desire-reasoning in the temporoparietal junction: evidence for specialization from functional near-infrared spectroscopy

PubMed Central

Bowman, Lindsay C.; Kovelman, Ioulia; Hu, Xiaosu; Wellman, Henry M.

2015-01-01

Behaviorally, children’s explicit theory of mind (ToM) proceeds in a progression of mental-state understandings: developmentally, children demonstrate accurate explicit desire-reasoning before accurate explicit belief-reasoning. Given its robust and cross-cultural nature, we hypothesize this progression may be paced in part by maturation/specialization of the brain. Neuroimaging research demonstrates that the right temporoparietal junction (TPJ) becomes increasingly selective for ToM reasoning as children age, and as their ToM improves. But this research has narrowly focused on beliefs or on undifferentiated mental-states. A recent ERP study in children included a critical contrast to desire-reasoning, and demonstrated that right posterior potentials differentiated belief-reasoning from desire-reasoning. Taken together, the literature suggests that children’s desire-belief progression may be paced by specialization of the right TPJ for belief-reasoning specifically, beyond desire-reasoning. In the present study, we tested this hypothesis directly by examining children’s belief- and desire-reasoning using functional near-infrared spectroscopy in conjunction with structural magnetic resonance imaging to pinpoint brain activation in the right TPJ. Results showed greatest activation in the right TPJ for belief-reasoning, beyond desire-reasoning, and beyond non-mental reasoning (control). Findings replicate and critically extend prior ERP results, and provide clear evidence for a specific neural mechanism underlying children’s progression from understanding desires to understanding beliefs. PMID:26500527

Country clustering applied to the water and sanitation sector: a new tool with potential applications in research and policy.

PubMed

Onda, Kyle; Crocker, Jonny; Kayser, Georgia Lyn; Bartram, Jamie

2014-03-01

The fields of global health and international development commonly cluster countries by geography and income to target resources and describe progress. For any given sector of interest, a range of relevant indicators can serve as a more appropriate basis for classification. We create a new typology of country clusters specific to the water and sanitation (WatSan) sector based on similarities across multiple WatSan-related indicators. After a literature review and consultation with experts in the WatSan sector, nine indicators were selected. Indicator selection was based on relevance to and suggested influence on national water and sanitation service delivery, and to maximize data availability across as many countries as possible. A hierarchical clustering method and a gap statistic analysis were used to group countries into a natural number of relevant clusters. Two stages of clustering resulted in five clusters, representing 156 countries or 6.75 billion people. The five clusters were not well explained by income or geography, and were distinct from existing country clusters used in international development. Analysis of these five clusters revealed that they were more compact and well separated than United Nations and World Bank country clusters. This analysis and resulting country typology suggest that previous geography- or income-based country groupings can be improved upon for applications in the WatSan sector by utilizing globally available WatSan-related indicators. Potential applications include guiding and discussing research, informing policy, improving resource targeting, describing sector progress, and identifying critical knowledge gaps in the WatSan sector. Copyright © 2013 Elsevier GmbH. All rights reserved.

A Review of Fulvestrant in Breast Cancer.

PubMed

Nathan, Mark R; Schmid, Peter

2017-01-01

Fulvestrant is a selective estrogen receptor degrader that binds, blocks and degrades the estrogen receptor (ER), leading to complete inhibition of estrogen signaling through the ER. This review article further explains the mechanism of action of the drug and goes on to review the trials carried out to optimize its dosing. Multiple trials have been undertaken to compare fulvestrant with other endocrine treatments, and results have shown it to have similar efficacy to anastrozole, tamoxifen and exemestane at 250 mg every 28 days. However, when given at 500 mg every 28 days, with an extra loading dose on day 14, it has demonstrated an improved progression-free survival (PFS) compared to anastrozole. We look at how fulvestrant has been used in combination with CDK4/6 inhibitors such as palbociclib (PALOMA-3) and ribociclib (MONALEESA-3) and drugs targeting the PI3K/AKT/mTOR pathway such as pictilisib (FERGI) and buparlisib (BELLE-2 and BELLE-3). We then go on to describe a selection of the ongoing clinical trials looking at combination therapy involving fulvestrant. Finally, we review the effect of fulvestrant in patients who have developed resistance to aromatase inhibitors via ESR1 mutation, where it has been shown to offer a PFS benefit that is further improved by the addition of the CDK4/6 inhibitor palbociclib. Whilst fulvestrant is clearly an effective drug as monotherapy, we believe that its role in the treatment of ER-positive breast cancer may be best reserved for combination therapy, and whilst there are multiple trials currently in progress, it would appear that the combination with CDK4/6 inhibitors would offer the greatest promise in terms of balancing benefit with toxicity.

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide

PubMed Central

Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T.; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry

2015-01-01

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients’ health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. PMID:25769541

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

PubMed

Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry

2015-06-01

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. Copyright© Ferrata Storti Foundation.

The use of process mapping in healthcare quality improvement projects.

PubMed

Antonacci, Grazia; Reed, Julie E; Lennox, Laura; Barlow, James

2018-05-01

Introduction Process mapping provides insight into systems and processes in which improvement interventions are introduced and is seen as useful in healthcare quality improvement projects. There is little empirical evidence on the use of process mapping in healthcare practice. This study advances understanding of the benefits and success factors of process mapping within quality improvement projects. Methods Eight quality improvement projects were purposively selected from different healthcare settings within the UK's National Health Service. Data were gathered from multiple data-sources, including interviews exploring participants' experience of using process mapping in their projects and perceptions of benefits and challenges related to its use. These were analysed using inductive analysis. Results Eight key benefits related to process mapping use were reported by participants (gathering a shared understanding of the reality; identifying improvement opportunities; engaging stakeholders in the project; defining project's objectives; monitoring project progress; learning; increased empathy; simplicity of the method) and five factors related to successful process mapping exercises (simple and appropriate visual representation, information gathered from multiple stakeholders, facilitator's experience and soft skills, basic training, iterative use of process mapping throughout the project). Conclusions Findings highlight benefits and versatility of process mapping and provide practical suggestions to improve its use in practice.

Sleep-dependent learning and motor-skill complexity

PubMed Central

Kuriyama, Kenichi; Stickgold, Robert; Walker, Matthew P.

2004-01-01

Learning of a procedural motor-skill task is known to progress through a series of unique memory stages. Performance initially improves during training, and continues to improve, without further rehearsal, across subsequent periods of sleep. Here, we investigate how this delayed sleep-dependent learning is affected when the task characteristics are varied across several degrees of difficulty, and whether this improvement differentially enhances individual transitions of the motor-sequence pattern being learned. We report that subjects show similar overnight improvements in speed whether learning a five-element unimanual sequence (17.7% improvement), a nine-element unimanual sequence (20.2%), or a five-element bimanual sequence (17.5%), but show markedly increased overnight improvement (28.9%) with a nine-element bimanual sequence. In addition, individual transitions within the motor-sequence pattern that appeared most difficult at the end of training showed a significant 17.8% increase in speed overnight, whereas those transitions that were performed most rapidly at the end of training showed only a non-significant 1.4% improvement. Together, these findings suggest that the sleep-dependent learning process selectively provides maximum benefit to motor-skill procedures that proved to be most difficult prior to sleep. PMID:15576888

Research on Hartmann test for progressive addition lenses

NASA Astrophysics Data System (ADS)

Qin, Lin-ling; Yu, Jing-chi

2009-05-01

Recently, in the world some growing-up measurements for Progressive addition lenses and relevant equipments have been developed. They are single point measurement, moiré deflectometry, Ronchi test techniques. Hartmann test for Progressive addition lenses is proposed in the article. The measurement principle of Hartmann test for ophthalmic lenses and the power compensation of off-axis rays are introduced. The experimental setup used to test lenses is put forward. For experimental test, a spatial filter is used for selecting a clean Gaussian beam; a collimating lens with focal distance f =300 mm is used to produce collimated beam. The Hartmann plate with a square array of holes separated at 2 mm is selected. The selection of laser and CCD camera is critical to the accuracy of experiment and the image processing algorithm. The spot patterns from CCD are obtained from the experimental tests. The power distribution map for lenses can be obtained by image processing in theory. The results indicate that Hartmann test for Progressive addition lenses is convenient and feasible; also its structure is simple.

Creating a dashboard to track progress toward IOM recommendations for the future of nursing.

PubMed

Spetz, Joanne; Bates, Timothy; Chu, Lela; Lin, Jessica; Fishman, Nancy W; Melichar, Lori

2013-01-01

This article explains the process used to identify and develop a set of data used to track national progress toward the recommendations of the Institute of Medicine Committee for the Future of Nursing. The data are presented in a dashboard format to visually summarize information and quickly measure progress. The approach selected by the research team is outlined, the criteria for selecting candidate metrics are detailed, the process for seeking external guidance is described, and the final dashboard measures are presented. Finally, the methods for data collection for each metric are explicated, to guide states and local regions in the collection of their own data.

The 12-week progressive quadriceps resistance training improves muscle strength, exercise capacity and quality of life in patients with stable chronic heart failure.

PubMed

Jankowska, Ewa A; Wegrzynowska, Kinga; Superlak, Malgorzata; Nowakowska, Katarzyna; Lazorczyk, Malgorzata; Biel, Bartosz; Kustrzycka-Kratochwil, Dorota; Piotrowska, Katarzyna; Banasiak, Waldemar; Wozniewski, Marek; Ponikowski, Piotr

2008-10-30

Abnormalities in the skeletal musculature underlie exercise intolerance in chronic heart failure (CHF). We investigated, whether in CHF selective resistance training without accompanying aerobic regime favourably affects muscle strength, muscle mass and improves exercise capacity. Ten patients with stable ischaemic CHF in NYHA class III (9 men, age: 70+/-6 years [mean+/-SD], left ventricular ejection fraction: 30+/-5%, peak oxygen consumption [peak VO(2)]: 12.4+/-3.0 mL/min/kg) underwent the rehabilitation programme which consisted of a 12-week training phase (progressive resistance exercises restricted to the quadriceps muscles) followed by a 12-week detraining phase. All subjects completed a training phase of the programme with no adverse events. Resistance training markedly increased quadriceps strength (right leg: 260+/-34 vs. 352+/-28 N, left leg: 264+/-38 vs. 342+/-30 N, both p<0.01 - all comparisons: baseline vs. after training), but did not affect lean tissue mass of lower extremities (both p>0.2). It was accompanied by an improvement in clinical status (all NYHA III vs. all NYHA II, p<0.01), quality of life (Minnesota questionnaire: 44+/-15 vs. 33+/-18 points, p<0.05), exercise capacity assessed using a distance during 6-minute walk test (6MWT: 362+/-83 vs. 455+/-71 m, p<0.01), but not peak VO(2) (p>0.2). Plasma NT-proBNP remained unchanged during the training. At the end of detraining phase, only a partial improvement in quadriceps strength (p<0.05), a 6MWT distance (p<0.05) and NYHA class (p=0.07 vs. baseline) persisted. Applied resistance quadriceps training is safe in patients with CHF. It increases muscle strength, improves clinical status, exercise capacity, and quality of life.

Smoke-free or not: a pilot evaluation in selected Beijing Hospitals

PubMed Central

2013-01-01

Background China enacted a policy to ban smoking in hospitals. The Chinese Association for Tobacco Control (CATC) developed a program to help hospitals implement this policy. They conducted a program and an assessment in 3 Chinese cities (Beijing, Shanghai and Guangdong). A more in-depth evaluation was implemented with a sub-sample of hospitals in Beijing (N = 7) to provide an independent assessment. This independent assessment focused on evaluating policy development and an assessment of secondhand smoke (SHS) to determine compliance with the smoke-free policy initiative. Methods Pre- and post-survey data were collected at each of the selected hospitals with a total sample of 2835 physicians at pre-intervention and 2812 at post-intervention. Smoking rates pre- and post-policy implementation, change in knowledge, attitudes and practices among physicians, and compliance with policy were assessed. Measurements of airborne nicotine concentrations in selected locations in each hospital were taken: main hospital lobby; main outpatient center; emergency waiting room; and stairwell adjacent to a large inpatient ward. Hospital policies were collected, translated and rated for incorporated components necessary to implement a smoke-free policy. Results Physicians’ smoking rates decreased and attitudes towards tobacco control improved significantly from pre-to post-intervention. Smoking was still reported in certain areas of the hospital with 96% of passive nicotine monitors as well as self-report indicating continued smoking. Nicotine levels ranged from <0.0056 to 3.94 μg/m3), with an overall mean of .667 μg/m3. Hospitals that established stronger policies seemed to have lower levels of nicotine, suggesting a relationship between policy development and compliance. This finding is interesting but just suggestive and requires further investigation to truly demonstrate if stronger policies improve compliance and produce better outcomes. Conclusion As implementation strategies for smoke-free environments are improved and more resources are focused on hospitals, China is making progress toward achieving smoke-free hospitals. Using a model program could increase the prevalence of SHS policies across China. However, relying only on survey data may not provide an accurate assessment of this progress, and more extensive evaluation efforts are useful to understand how change can and does occur. PMID:24134057

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

PubMed Central

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

Patterns of neuroAIDS in Africa.

PubMed

Tadesse, Tizeta; Langford, Dianne; Manji, Karim; Mehari, Enawgaw

2005-01-01

According to UNAIDS, the African population accounts for greater than half of persons infected with HIV. Nevertheless, little information exists characterizing HIV in this population. Thus, the natural history and progression of HIV in the African population is virtually undocumented and therefore, poorly understood. Information regarding virtually every aspect of the disease including microbiology, pathogenicity, virulence, and clinical manifestation is based largely on data from select and limited populations. During the HAART-era, we have seen dramatic and significant changes in patterns of NeuroAIDS in patients in clinical cohorts from the United States and Western Europe. These observations have led to increased understanding of the progression of NeuroAIDS and have improved our ability to design treatment regimens to combat CNS complications resulting from HIV. Despite the existence of antiretroviral therapy for HIV, its absence in Africa along with poor treatments for opportunistic infections associated with HIV have become the main sources of neurological morbidity and mortality. In this context, we are presented with a unique opportunity to cultivate and enhance our understanding of the natural history and progression of NeuroAIDS in the African population thereby, better equipping healthcare providers, patients and their families in addressing this epidemic. This concept is particularly important as rapidly improving and more accessible anti-HIV medications and medications for the treatment of opportunistic infections become available to third world countries such as Africa. We believe that it is imperative to foster research, education and training between institutions in the industrialized world and Africa to close the gap in understanding patterns of NeuroAIDS in Africa.

An Examination of Principal Leadership Styles and Their Influence on School Performance as Measured by Adequate Yearly Progress at Selected Title I Elementary Schools in South Carolina

ERIC Educational Resources Information Center

Martin, Tammy Faith

2012-01-01

The purpose of this study was to examine principal leadership styles and their influence on school performance as measured by adequate yearly progress at selected Title I schools in South Carolina. The main focus of the research study was to complete descriptive statistics on principal leadership styles in schools that met or did not meet adequate…

Effect of progressive muscle relaxation versus intake of ginger powder on dysmenorrhoea amongst the nursing students in Pune.

PubMed

Halder, Annesa

2012-01-01

The present study was conducted to examine the comparative efficacy of progressive muscle relaxation and the oral intake of ginger on symptoms of dysmenorrhoea among nursing students of Pune, Maharashtra. The study students (n = 75) were divided into three groups, two experimental and one control Ginger powder 1 gm per dose was administered twice a day with warm water after meal to the second experimental group during the first three days of their menstruation. Main outcome measures were the severity of selected symptoms of dysmenorrhoea. The daily symptom calendar, a 5-point Likert Scale was used to assess the severity of selected symptoms of dysmenorrhoea. Main outcome measures were the severity of selected symptoms of dysmenorrhoea, which were analysed using MANOVA. It was concluded that in treating symptoms of dysmenorrhoea, ginger powder has efficacy superior to progressive muscle relaxation.

Examining gender equity in health policies in a low- (Peru), middle- (Colombia), and high- (Canada) income country in the Americas.

PubMed

Stewart, Donna E; Dorado, Linda M; Diaz-Granados, Natalia; Rondon, Marta; Saavedra, Javier; Posada-Villa, Jose; Torres, Yolanda

2009-12-01

Gender inequities in health prevail in most countries despite ongoing attempts to eliminate them. Assessment of gender-sensitive health policies can be used to identify country specific progress as well as gaps and issues that need to be addressed to meet health equity goals. This study selected and measured the existence of gender-sensitive health policies in a low- (Peru), middle- (Colombia), and high (Canada)-income country in the Americas. Investigators selected 10 of 20 gender-sensitive health policy indicators and found eight to be feasible to measure in all three countries, although the wording and scope varied. The results from this study inform policy makers and program planners who aim to develop, improve, implement, and monitor national gender-sensitive health policies. Future studies should assess the implementation of policy indicators within countries and assess their performance in increasing gender equity.

An update on the use and investigation of probiotics in health and disease

PubMed Central

Sanders, Mary Ellen; Guarner, Francisco; Guerrant, Richard; Holt, Peter R; Quigley, Eamonn MM; Sartor, R Balfour; Sherman, Philip M; Mayer, Emeran A

2014-01-01

Probiotics are derived from traditional fermented foods, from beneficial commensals or from the environment. They act through diverse mechanisms affecting the composition or function of the commensal microbiota and by altering host epithelial and immunological responses. Certain probiotic interventions have shown promise in selected clinical conditions where aberrant microbiota have been reported, such as atopic dermatitis, necrotising enterocolitis, pouchitis and possibly irritable bowel syndrome. However, no studies have been conducted that can causally link clinical improvements to probiotic-induced microbiota changes. Whether a disease-prone microbiota pattern can be remodelled to a more robust, resilient and disease-free state by probiotic administration remains a key unanswered question. Progress in this area will be facilitated by: optimising strain, dose and product formulations, including protective commensal species; matching these formulations with selectively responsive subpopulations; and identifying ways to manipulate diet to modify bacterial profiles and metabolism. PMID:23474420

Silodosin in the treatment of benign prostatic hyperplasia

PubMed Central

Rossi, Maxime; Roumeguère, Thierry

2010-01-01

Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for α1A-adrenergic receptors, as compared with both α1B- and α1D -adrenoceptors, exceeding the selectivity of all currently used α1-blockers, and with clinically promising effects. PMID:21116335

Nanomaterial-based electrochemical sensors for arsenic - A review.

PubMed

Kempahanumakkagari, Sureshkumar; Deep, Akash; Kim, Ki-Hyun; Kumar Kailasa, Suresh; Yoon, Hye-On

2017-09-15

The existence of arsenic in the environment poses severe global health threats. Considering its toxicity, the sensing of arsenic is extremely important. Due to the complexity of environmental and biological samples, many of the available detection methods for arsenic have serious limitations on selectivity and sensitivity. To improve sensitivity and selectivity and to circumvent interferences, different electrode systems have been developed based on surface modification with nanomaterials including carbonaceous nanomaterials, metallic nanoparticles (MNPs), metal nanotubes (MNTs), and even enzymes. Despite the progress made in electrochemical sensing of arsenic, some issues still need to be addressed to realize cost effective, portable, and flow-injection type sensor systems. The present review provides an in-depth evaluation of the nanoparticle-modified electrode (NME) based methods for the electrochemical sensing of arsenic. NME based sensing systems are projected to become an important option for monitoring hazardous pollutants in both environmental and biological media. Copyright © 2017 Elsevier B.V. All rights reserved.

New molecules and old drugs as emerging approaches to selectively target human glioblastoma cancer stem cells.

PubMed

Würth, Roberto; Barbieri, Federica; Florio, Tullio

2014-01-01

Despite relevant progress obtained by multimodal treatment, glioblastoma (GBM), the most aggressive primary brain tumor, is still incurable. The most encouraging advancement of GBM drug research derives from the identification of cancer stem cells (CSCs), since these cells appear to represent the determinants of resistance to current standard therapies. The goal of most ongoing studies is to identify drugs able to affect CSCs biology, either inducing selective toxicity or differentiating this tumor cell population into nontumorigenic cells. Moreover, the therapeutic approach for GBM could be improved interfering with chemo- or radioresistance mechanisms, microenvironment signals, and the neoangiogenic process. During the last years, molecular targeted compounds such as sorafenib and old drugs, like metformin, displayed interesting efficacy in preclinical studies towards several tumors, including GBM, preferentially affecting CSC viability. In this review, the latest experimental results, controversies, and prospective application concerning these promising anticancer drugs will be discussed.

[Progress in heavy particle radiotherapy].

PubMed

Tsujii, H; Tsuji, H; Okumura, T

1994-06-01

In recent years, new types of ionizing radiations have been used as an attractive modality in cancer treatments. Low LET radiation such as protons and helium ions has the advantage of a high physical selectivity of irradiation. Clinical results have confirmed that they are of benefit in certain types of cancer. High LET particles such as fast neutrons, heavy ions (carbon, neon) and negative pions possess higher radiobiological effects (RBE). Moreover, the latter two particles have an advantage of improved dose distribution. The clinical indications for protons are those located in close vicinity to the critical normal organs, and those for fast neutrons are relatively superficial tumors. Further studies are needed to determine indications for pions. The available clinical experience in selected tumors with protons, pions and fast neutrons justifies the heavy-ion therapy programs. Successful results are anticipated from HIMAC (Heavy ion medical accelerator in Chiba) which is a dedicated facility for heavy-ion therapy.

Robust optimization model and algorithm for railway freight center location problem in uncertain environment.

PubMed

Liu, Xing-Cai; He, Shi-Wei; Song, Rui; Sun, Yang; Li, Hao-Dong

2014-01-01

Railway freight center location problem is an important issue in railway freight transport programming. This paper focuses on the railway freight center location problem in uncertain environment. Seeing that the expected value model ignores the negative influence of disadvantageous scenarios, a robust optimization model was proposed. The robust optimization model takes expected cost and deviation value of the scenarios as the objective. A cloud adaptive clonal selection algorithm (C-ACSA) was presented. It combines adaptive clonal selection algorithm with Cloud Model which can improve the convergence rate. Design of the code and progress of the algorithm were proposed. Result of the example demonstrates the model and algorithm are effective. Compared with the expected value cases, the amount of disadvantageous scenarios in robust model reduces from 163 to 21, which prove the result of robust model is more reliable.

Lung abscess combined with chronic osteomyelitis of the mandible successfully treated with video-assisted thoracoscopic surgery.

PubMed

Arai, Hiromasa; Inui, Kenji; Watanabe, Keisuke; Watanuki, Kei; Okudela, Koji; Tsuboi, Masahiro; Masuda, Munetaka

2015-04-01

With the progress of antibiotic therapy, the mortality of lung abscess has been improved, and surgical intervention has declined. However, surgery is still required in selected cases that are intractable to antibiotic treatment. Video-assisted thoracoscopic surgery (VATS) is beneficial for treatment and/or diagnosis of pulmonary disease as it provides a less invasive surgical technique and reduces prolongation of post-operative recovery. However, the indication of VATS lobectomy for lung abscess is controversial as a result of particular complications, i.e. wet lung, intrapleural adhesion and ease of bleeding. We herein report a rare combination of lung abscess and osteomyelitis of mandible resulting from the same pathogen successfully treated with VATS lobectomy. We propose VATS lobectomy for lung abscess. This procedure might be the best treatment candidate for selected cases of lung abscess. © 2014 John Wiley & Sons Ltd.

Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.

PubMed

Ikegami, Tohru; Tanaka, Nobuo

2016-06-12

Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.

Application of Composite Mechanics to Composites Enhanced Concrete Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Gotsis, Pascal K.

2006-01-01

A new and effective method is described to design composites to repair damage or enhance the overload strength of concrete infrastructures. The method is based on composite mechanics which is available in computer codes. It is used to simulate structural sections made from reinforced concrete which are typical in infrastructure as well as select reinforced concrete structures. The structural sections are represented by a number of layers through the thickness where different layers are used in concrete, and for the composite. The reinforced concrete structures are represented with finite elements where the element stiffness parameters are from the structural sections which are represented by composite mechanics. The load carrying capability of the structure is determined by progressive structural fracture. Results show up to 40 percent improvements for damage and for overload enhancement with relatively small laminate thickness for the structural sections and up to three times for the composite enhanced select structures (arches and domes).

The roles of talent, physical precocity and practice in the development of soccer expertise.

PubMed

Helsen, W F; Hodges, N J; Van Winckel, J; Starkes, J L

2000-09-01

Here we consider the potential contributions of talent, physical precocity and deliberate practice in the development of soccer expertise. After presenting a working definition of 'talent', we examine how coaches perceive and select potential talent. Our findings suggest that much of what coaches see as early talent may be explained by physical precocity associated with a relative age advantage. Finally, as a test of the model of Deliberate Practice, we review the results of studies that assessed the progress of international, national and provincial players based on accumulated practice, amount of practice per week and relative importance and demands of various practice and everyday activities. A positive linear relationship was found between accumulated individual plus team practice and skill. Various practical suggestions can be made to improve talent detection and selection and to optimize career practice patterns in soccer.

ECUT: Energy Conversion and Utilization Technologies program. Heterogeneous catalysis modeling program concept

NASA Technical Reports Server (NTRS)

Voecks, G. E.

1983-01-01

Insufficient theoretical definition of heterogeneous catalysts is the major difficulty confronting industrial suppliers who seek catalyst systems which are more active, selective, and stable than those currently available. In contrast, progress was made in tailoring homogeneous catalysts to specific reactions because more is known about the reaction intermediates promoted and/or stabilized by these catalysts during the course of reaction. However, modeling heterogeneous catalysts on a microscopic scale requires compiling and verifying complex information on reaction intermediates and pathways. This can be achieved by adapting homogeneous catalyzed reaction intermediate species, applying theoretical quantum chemistry and computer technology, and developing a better understanding of heterogeneous catalyst system environments. Research in microscopic reaction modeling is now at a stage where computer modeling, supported by physical experimental verification, could provide information about the dynamics of the reactions that will lead to designing supported catalysts with improved selectivity and stability.

Judicious use of biologicals in juvenile idiopathic arthritis.

PubMed

Zhao, Yongdong; Wallace, Carol

2014-11-01

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder that may cause joint destruction. Biological treatments targeting specific cytokines and cell interactions have transformed the outcomes of JIA. This review focuses on the selection of patients for and the timing and selection of biological treatment in JIA. Tumor necrosis factor (TNF) inhibitors remain the first choice for polyarticular JIA, followed by abatacept and tocilizumab. Monoclonal-antibody TNF inhibitors and abatacept are usually chosen for methotrexate-resistant uveitis. Recent clinical trials of canakinumab, rilonacept, and tocilizumab have obtained great improvement in both systemic and arthritic features in chronic systemic JIA patients. Current guidelines support the early use of a short-acting IL-1 antagonist for macrophage activation syndrome, a life-threatening complication. TREAT and ACUTE studies suggest that a therapeutic window of opportunity during early disease may exist in JIA. Early initiation of biological therapy may be associated with slower progression of joint damage and longer remission.

Improvements in cloning efficiencies may be possible by increasing uniformity in recipient oocytes and donor cells.

PubMed

Miyoshi, Kazuchika; Rzucidlo, S Jacek; Pratt, Scott L; Stice, Steven L

2003-04-01

The low efficiency of somatic cell cloning is the major obstacle to widespread use of this technology. Incomplete nuclear reprogramming following the transfer of donor nuclei into recipient oocytes has been implicated as a primary reason for the low efficiency of the cloning procedure. The mechanisms and factors that affect the progression of the nuclear reprogramming process have not been completely elucidated, but the identification of these factors and their subsequent manipulation would increase cloning efficiency. At present, many groups are studying donor nucleus reprogramming. Here, we present an approach in which the efficiency of producing viable offspring is improved by selecting recipient oocytes and donor cells that will produce cloned embryos with functionally reprogrammed nuclei. This approach will produce information useful in future studies aimed at further deciphering the nuclear reprogramming process.

Bevacizumab in ovarian cancer: A critical review of phase III studies

PubMed Central

Rossi, Luigi; Verrico, Monica; Zaccarelli, Eleonora; Papa, Anselmo; Colonna, Maria; Strudel, Martina; Vici, Patrizia; Bianco, Vincenzo; Tomao, Federica

2017-01-01

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment. PMID:27852039

Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study.

PubMed

Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

2017-01-07

BACKGROUND In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. MATERIAL AND METHODS The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A - conventional TENS, B - acupuncture-like TENS, C - high-voltage electrical stimulation, D - interferential current stimulation, E - diadynamic current, and F - control group. RESULTS The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. CONCLUSIONS Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain.

Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study

PubMed Central

Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

2017-01-01

Background In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. Material/Methods The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A – conventional TENS, B – acupuncture-like TENS, C – high-voltage electrical stimulation, D – interferential current stimulation, E – diadynamic current, and F – control group. Results The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. Conclusions Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain. PMID:28062862

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

PubMed Central

Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

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

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Phrenic Nerve Stimulation: Technology and Clinical Applications.

PubMed

Abdunnur, Shane V; Kim, Daniel H

2015-01-01

Phrenic nerve stimulation is a technique used to reanimate the diaphragm of patients with central nervous system etiologies of respiratory insufficiency. Current clinical indications include congenital central hypoventilation syndrome, spinal cord injury above C4, brain stem injury, and idiopathic severe sleep apnea. Presurgical evaluation ensures proper patient selection by validating the intact circuit from the phrenic nerve through alveolar oxygenation. The procedure involves placing leads around the phrenic nerves bilaterally and attaching these leads to radio receivers in a subcutaneous pocket. The rate and amplitude of the current is adjusted via an external radio transmitter. After implantation, each patient progresses through a conditioning phase that strengthens the diaphragm and progressively provides independence from the mechanical ventilator. Studies indicate that patients and families experience an improved quality of life and are satisfied with the results. Phrenic nerve stimulation provides a safe and effective means for reanimating the diaphragm for certain patients with respiratory insufficiency, providing independence from mechanical ventilation. © 2016 S. Karger AG, Basel.

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

PubMed

Sharpe, Martyn A; Livingston, Andrew D; Gist, Taylor L; Ghosh, Pardip; Han, Junyan; Baskin, David S

2015-09-01

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

PubMed Central

Sharpe, Martyn A.; Livingston, Andrew D.; Gist, Taylor L.; Ghosh, Pardip; Han, Junyan; Baskin, David S.

2015-01-01

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P+-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models. PMID:26501110

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Build YOUR All-Sky View with Aladin

NASA Astrophysics Data System (ADS)

Oberto, A.; Fernique, P.; Boch, T.; Bonnarel, F.

2011-07-01

From the need to extend the display outside the boundaries of a single image, the Aladin team recently developed a new feature to visualize wide areas or even all of the sky. This all-sky view is particularly useful for visualization of very large objects and, with coverage of the whole sky, maps from the Planck satellite. To improve on this capability, some catalogs and maps have been built from many surveys (e.g., DSS, IRIS, GLIMPSE, SDSS, 2MASS) in mixed resolutions, allowing progressive display. The maps are constructed by mosaicing individual images. Now, we provide a new tool to build an all-sky view with your own images. From the images you have selected, it will compose a mosaic with several resolutions (HEALPix tessellation), and organize them to allow their progressive display in Aladin. For convenience, you can export it to a HEALPix map, or share it with the community through Aladin from your web site or eventually from the CDS image collection.

Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program.

PubMed

Wang, Ying; Edalji, Rohinton P; Panchal, Sanjay C; Sun, Chaohong; Djuric, Stevan W; Vasudevan, Anil

2017-10-26

It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k off ) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K i and k off . Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

Lack of coordination between health policy and medical education: a contributing factor to the resignation of specialist trainees in Fiji?

PubMed

Oman, Kimberly M; Usher, Kim; Moulds, Rob

2009-03-13

Specialist training was established in Fiji in 1998. This study explored whether health policy, and in particular mismatches between existing policy and the new realities of local specialist training, contributed to decisions by many trainees to ultimately leave the public sectors, often to migrate. Data was collected on the whereabouts of all specialist trainees. Semi-structured interviews were carried out with 36 of 66 Fiji trainees in order to explore reasons for continuing or not completing training, as well as the reasons behind subsequent career choices. Overall, 54.5% of doctors remained in the public sectors or were temporarily overseas. Completion of specialist training was particularly associated with improved retention. Policies that contributed to frustration and sometimes resignations included a lack of transparency in the selection of doctors to enter training pathways, and unreliable career progression following completion of training. Doctors who left training before completion mentioned family stresses, which were exacerbated by delayed age at entry into training and a lack of certainty in regards to the timing of improved working conditions through career advancement. Policy adjustments to expedite entry into training, as well as to establish predictable career progression as a reward for training may increase training completions and overall retention.

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

Rhinefrank, Kenneth; Lamb, Bradford; Prudell, Joseph

This Project aims to satisfy objectives of the DOE’s Water Power Program by completing a system detailed design (SDD) and other important activities in the first phase of a utility-scale grid-connected ocean wave energy demonstration. In early 2012, Columbia Power (CPwr) had determined that further cost and performance optimization was necessary in order to commercialize its StingRAY wave energy converter (WEC). CPwr’s progress toward commercialization, and the requisite technology development path, were focused on transitioning toward a commercial-scale demonstration. This path required significant investment to be successful, and the justification for this investment required improved annual energy production (AEP) andmore » lower capital costs. Engineering solutions were developed to address these technical and cost challenges, incorporated into a proposal to the US Department of Energy (DOE), and then adapted to form the technical content and statement of project objectives of the resulting Project (DE-EE0005930). Through Project cost-sharing and technical collaboration between DOE and CPwr, and technical collaboration with Oregon State University (OSU), National Renewable Energy Lab (NREL) and other Project partners, we have demonstrated experimentally that these conceptual improvements have merit and made significant progress towards a certified WEC system design at a selected and contracted deployment site at the Wave Energy Test Site (WETS) at the Marine Corps Base in Oahu, HI (MCBH).« less

Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

PubMed Central

Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

2016-01-01

Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

PubMed

Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

2018-04-18

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

Symposium review: Novel strategies to genetically improve mastitis resistance in dairy cattle.

PubMed

Martin, P; Barkema, H W; Brito, L F; Narayana, S G; Miglior, F

2018-03-01

Mastitis is a disease of major economic importance to the dairy cattle sector because of the high incidence of clinical mastitis and prevalence of subclinical mastitis and, consequently, the costs associated with treatment, production losses, and reduced animal welfare. Disease-recording systems compiling data from a large number of farms are still not widely implemented around the world; thus, selection for mastitis resistance is often based on genetically correlated indicator traits such as somatic cell count (SCC), udder depth, and fore udder attachment. However, in the past years, several countries have initiated collection systems of clinical mastitis, based on producers recording data in most cases. The large data sets generated have enabled researchers to assess incidence of this disease and to investigate the genetic background of clinical mastitis itself, as well as its relationships with other traits of interest to the dairy industry. The genetic correlations between clinical mastitis and its previous proxies were estimated more accurately and confirmed the strong relationship of clinical mastitis with SCC and udder depth. New traits deriving from SCC were also studied, with the most relevant findings being associated with mean somatic cell score (SCS) in early lactation, standard deviation of SCS, and excessive test-day SCC pattern. Genetic correlations between clinical mastitis and other economically important traits indicated that selection for mastitis resistance would also improve resistance against other diseases and enhance both fertility and longevity. However, milk yield remains negatively correlated with clinical mastitis, emphasizing the importance of including health traits in the breeding objectives to achieve genetic progress for all important traits. These studies enabled the establishment of new genetic and genomic evaluation models, which are more efficient for selection to mastitis resistance. Further studies that are potential keys for future improvement of mastitis resistance are deep investigation of the bacteriology of mastitis, identification of novel indicator traits and tools for selection, and development of a larger female reference population to improve reliability of genomic evaluations. These cutting-edge studies will result in a better understanding of the genetic background of mastitis resistance and enable a more accurate phenotyping and genetic selection to improve mastitis resistance, and consequently, animal welfare and industry profitability. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers.

PubMed

Marizzoni, Moira; Ferrari, Clarissa; Jovicich, Jorge; Albani, Diego; Babiloni, Claudio; Cavaliere, Libera; Didic, Mira; Forloni, Gianluigi; Galluzzi, Samantha; Hoffmann, Karl-Titus; Molinuevo, José Luis; Nobili, Flavio; Parnetti, Lucilla; Payoux, Pierre; Ribaldi, Federica; Rossini, Paolo Maria; Schönknecht, Peter; Soricelli, Andrea; Hensch, Tilman; Tsolaki, Magda; Visser, Pieter Jelle; Wiltfang, Jens; Richardson, Jill C; Bordet, Régis; Blin, Olivier; Frisoni, Giovanni B

2018-06-09

Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients. To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression. APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort. Linear mixed models were performed 1) with baseline structural biomarker, time, and biomarker×time interaction as factors to predict longitudinal changes in ADAS-cog13, 2) with Aβ42/P-tau status, time, and Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in MRI measures, and 3) to compute sample size estimation for a trial implemented with the selected biomarkers. Only baseline lateral ventricle volume was able to identify a subgroup of prodromal AD patients who declined faster (interaction, p = 0.003). Lateral ventricle volume and medial temporal lobe measures were the biomarkers most sensitive to disease progression (interaction, p≤0.042). Enrichment through ventricular volume reduced the sample size that a clinical trial would require from 13 to 76%, depending on structural outcome variable. The biomarker needing the lowest sample size was the hippocampal subfield GC-ML-DG (granule cells of molecular layer of the dentate gyrus) (n = 82 per arm to demonstrate a 20% atrophy reduction). MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.

Islet Transplantation in Type 1 Diabetes: Ongoing Challenges, Refined Procedures, and Long-Term Outcome

PubMed Central

Shapiro, A.M. James

2012-01-01

Remarkable progress has been made in islet transplantation over a span of 40 years. Once just an experimental curiosity in mice, this therapy has moved forward, and can now provide robust therapy for highly selected patients with type 1 diabetes (T1D), refractory to stabilization by other means. This progress could not have occurred without extensive dynamic international collaboration. Currently, 1,085 patients have undergone islet transplantation at 40 international sites since the Edmonton Protocol was reported in 2000 (752 allografts, 333 autografts), according to the Collaborative Islet Transplant Registry. The long-term results of islet transplantation in selected centers now match registry data of pancreas-alone transplantation, with 6 sites reporting five-year insulin independence rates ≥50%. Islet transplantation has been criticized for the use of multiple donor pancreas organs, but progress has also occurred in single-donor success, with 10 sites reporting increased single-donor engraftment. The next wave of innovative clinical trial interventions will address instant blood-mediated inflammatory reaction (IBMIR), apoptosis, and inflammation, and will translate into further marked improvements in single-donor success. Effective control of auto- and alloimmunity is the key to long-term islet function, and high-resolution cellular and antibody-based assays will add considerable precision to this process. Advances in immunosuppression, with new antibody-based targeting of costimulatory blockade and other T-B cellular signaling, will have further profound impact on the safety record of immunotherapy. Clinical trials will move forward shortly to test out new human stem cell derived islets, and in parallel trials will move forward, testing pig islets for compatibility in patients. Induction of immunological tolerance to self-islet antigens and to allografts is a difficult challenge, but potentially within our grasp. PMID:23804275

Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study.

PubMed

Weiss, Brian; Widemann, Brigitte C; Wolters, Pamela; Dombi, Eva; Vinks, Alexander; Cantor, Alan; Perentesis, John; Schorry, Elizabeth; Ullrich, Nicole; Gutmann, David H; Tonsgard, James; Viskochil, David; Korf, Bruce; Packer, Roger J; Fisher, Michael J

2015-04-01

Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3-23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An exploratory study into the effect of time-restricted internet access on face-validity, construct validity and reliability of postgraduate knowledge progress testing

PubMed Central

2013-01-01

Background Yearly formative knowledge testing (also known as progress testing) was shown to have a limited construct-validity and reliability in postgraduate medical education. One way to improve construct-validity and reliability is to improve the authenticity of a test. As easily accessible internet has become inseparably linked to daily clinical practice, we hypothesized that allowing internet access for a limited amount of time during the progress test would improve the perception of authenticity (face-validity) of the test, which would in turn improve the construct-validity and reliability of postgraduate progress testing. Methods Postgraduate trainees taking the yearly knowledge progress test were asked to participate in a study where they could access the internet for 30 minutes at the end of a traditional pen and paper test. Before and after the test they were asked to complete a short questionnaire regarding the face-validity of the test. Results Mean test scores increased significantly for all training years. Trainees indicated that the face-validity of the test improved with internet access and that they would like to continue to have internet access during future testing. Internet access did not improve the construct-validity or reliability of the test. Conclusion Improving the face-validity of postgraduate progress testing, by adding the possibility to search the internet for a limited amount of time, positively influences test performance and face-validity. However, it did not change the reliability or the construct-validity of the test. PMID:24195696

A controlled single-case treatment of severe long-term selective mutism in a child with mental retardation.

PubMed

Facon, Bruno; Sahiri, Safia; Rivière, Vinca

2008-12-01

The aim of the present study was to demonstrate the efficacy of combining two operant learning procedures--shaping and fading--for treating selective mutism. The participant was a 12-year-old boy with mental retardation presenting a severe long-term selective mutism. The treatment was aimed at increasing the loudness of his vocalizations in an increasingly social milieu. The treatment was conducted over the course of about 20 weeks, with four 15-minute sessions per week. A gradual increase in speech loudness was observed. Data indicated a close correspondence between the changes in speech loudness and the criteria for reinforcement successively applied by the therapist, thereby confirming the causal link between the child's progress and the changes in reinforcement contingencies. In addition, good generalization was noted during the stimulus fading phase. Six-month follow up showed that loudness of verbalizations was still satisfactory in the classroom despite a change of school and peer group. The impressive improvement of the child's verbal behavior shows that the implementation of a treatment package including both shaping and stimulus fading is a worthwhile therapeutic option, even in the case of severe long-term selective mutism associated with mental retardation.

Assessing Chronic Illness Care Education (ACIC-E): a tool for tracking educational re-design for improving chronic care education.

PubMed

Bowen, Judith L; Provost, Lloyd; Stevens, David P; Johnson, Julie K; Woods, Donna M; Sixta, Connie S; Wagner, Edward H

2010-09-01

Recent Breakthrough Series Collaboratives have focused on improving chronic illness care, but few have included academic practices, and none have specifically targeted residency education in parallel with improving clinical care. Tools are available for assessing progress with clinical improvements, but no similar instruments have been developed for monitoring educational improvements for chronic care education. To design a survey to assist teaching practices with identifying curricular gaps in chronic care education and monitor efforts to address those gaps. During a national academic chronic care collaborative, we used an iterative method to develop and pilot test a survey instrument modeled after the Assessing Chronic Illness Care (ACIC). We implemented this instrument, the ACIC-Education, in a second collaborative and assessed the relationship of survey results with reported educational measures. A combined 57 self-selected teams from 37 teaching hospitals enrolled in one of two collaboratives. We used descriptive statistics to report mean ACIC-E scores and educational measurement results, and Pearson's test for correlation between the final ACIC-E score and reported educational measures. A total of 29 teams from the national collaborative and 15 teams from the second collaborative in California completed the final ACIC-E. The instrument measured progress on all sub-scales of the Chronic Care Model. Fourteen California teams (70%) reported using two to six education measures (mean 4.3). The relationship between the final survey results and the number of educational measures reported was weak (R(2) = 0.06, p = 0.376), but improved when a single outlier was removed (R(2) = 0.37, p = 0.022). The ACIC-E instrument proved feasible to complete. Participating teams, on average, recorded modest improvement in all areas measured by the instrument over the duration of the collaboratives. The relationship between the final ACIC-E score and the number of educational measures was weak. Further research on its utility and validity is required.

Effect of Adventitious Carbon on the Environmental Degradation of SiC/BN/SiC Composites

NASA Technical Reports Server (NTRS)

Ogbuji, L. U. J. T.; Yun, H. M.; DiCarlo, J.

2002-01-01

Pesting remains a major obstacle to the application of SiC/SiC composites in engine service and selective degradation of the boron nitride interphase at intermediate temperatures is of primary concern. However, significant progress has been made on interphase improvement recently and we now know more about the phenomenon and ways to suppress it. By screening SiC/BN/SiC materials through characterization of strength and microstructures after exposure in a burner rig, some factors that control pesting in these composites have been determined. A key precaution is careful control of elemental carbon presence in the interphase region.

Novel approaches to increasing the brightness of broad area lasers

NASA Astrophysics Data System (ADS)

Crump, P.; Winterfeldt, M.; Decker, J.; Ekterai, M.; Fricke, J.; Knigge, S.; Maaßdorf, A.; Erbert, G.

2016-03-01

Progress in studies to increase the lateral brightness Blat of broad area lasers is reviewed. Blat=Pout/BPPlat is maximized by developing designs and technology for lowest lateral beam parameter product, BPPlat, at highest optical output power Pout. This can be achieved by limiting the number of guided lateral modes and by improving the beam quality of low-order lateral modes. Important effects to address include process and packaging induced wave-guiding, lateral carrier accumulation and the thermal lens profile. A careful selection of vertical design is also shown to be important, as are advanced techniques to filter out higher order modes.

Clinical Decision Support: a 25 Year Retrospective and a 25 Year Vision.

PubMed

Middleton, B; Sittig, D F; Wright, A

2016-08-02

The objective of this review is to summarize the state of the art of clinical decision support (CDS) circa 1990, review progress in the 25 year interval from that time, and provide a vision of what CDS might look like 25 years hence, or circa 2040. Informal review of the medical literature with iterative review and discussion among the authors to arrive at six axes (data, knowledge, inference, architecture and technology, implementation and integration, and users) to frame the review and discussion of selected barriers and facilitators to the effective use of CDS. In each of the six axes, significant progress has been made. Key advances in structuring and encoding standardized data with an increased availability of data, development of knowledge bases for CDS, and improvement of capabilities to share knowledge artifacts, explosion of methods analyzing and inferring from clinical data, evolution of information technologies and architectures to facilitate the broad application of CDS, improvement of methods to implement CDS and integrate CDS into the clinical workflow, and increasing sophistication of the end-user, all have played a role in improving the effective use of CDS in healthcare delivery. CDS has evolved dramatically over the past 25 years and will likely evolve just as dramatically or more so over the next 25 years. Increasingly, the clinical encounter between a clinician and a patient will be supported by a wide variety of cognitive aides to support diagnosis, treatment, care-coordination, surveillance and prevention, and health maintenance or wellness.

Molecular progress on the mapping and cloning of functional genes for blast disease in rice (Oryza sativa L.): current status and future considerations.

PubMed

Ashkani, S; Rafii, M Y; Shabanimofrad, M; Ghasemzadeh, A; Ravanfar, S A; Latif, M A

2016-01-01

Rice blast disease, which is caused by the fungal pathogen Magnaporthe oryzae, is a recurring problem in all rice-growing regions of the world. The use of resistance (R) genes in rice improvement breeding programmes has been considered to be one of the best options for crop protection and blast management. Alternatively, quantitative resistance conferred by quantitative trait loci (QTLs) is also a valuable resource for the improvement of rice disease resistance. In the past, intensive efforts have been made to identify major R-genes as well as QTLs for blast disease using molecular techniques. A review of bibliographic references shows over 100 blast resistance genes and a larger number of QTLs (∼500) that were mapped to the rice genome. Of the blast resistance genes, identified in different genotypes of rice, ∼22 have been cloned and characterized at the molecular level. In this review, we have summarized the reported rice blast resistance genes and QTLs for utilization in future molecular breeding programmes to introgress high-degree resistance or to pyramid R-genes in commercial cultivars that are susceptible to M. oryzae. The goal of this review is to provide an overview of the significant studies in order to update our understanding of the molecular progress on rice and M. oryzae. This information will assist rice breeders to improve the resistance to rice blast using marker-assisted selection which continues to be a priority for rice-breeding programmes.

Montreal's experience with Cyranose heat and moisture exchanger use in 15 laryngectomized patients.

PubMed

Dupuis, Paule; Guertin, Louis; Rainville, Marie-Stéphane; Prud'homme, Dominique-Louise; Lavigne, François

2007-08-01

Evaluate the effects of the improvement of filtration, heating and humidification of inspired air with Cyranose heat and moisture exchanger (HME) on voice quality, breathing, and secretion handling in laryngectomized patients. Prospective study. Fifteen laryngectomized patients, mean age 68, ages ranging from 50 to 91 years. Information was given to patients through video and brochures. Patients were selected if they had minimal understanding, permanent decanulization, no tumour progression or bronchopulmonary infections, and received no recent radiation therapy treatment. They were given the prosthesis and a starter kit. They were then evaluated by a speech pathologist with a structured questionnaire after one week, one month, and three months. The outcomes measured were comfort, breathing, secretions, and ease of use of the prosthesis as well as its effect on voice. Impressions of patients on humidification, filtration, and heating of inspired air were also recorded. At conclusion of trial, 75% of patients wore the prosthesis on a daily basis and they all found it easy to use. All patients who completed the trial found breathing and handling of secretions easier as they thought humidification and filtration of air had improved. Quality of voice improved for 50% while remaining unchanged for 37%. The positive effect of the prosthesis progressed throughout the trial. Seven patients dropped out of the trial, mainly because of adhesive-related issues. Laryngectomized patients from the Montreal area could benefit from Cyranose artificial nose following an adaptation period during our cold winter.

Advances in Agrobacterium tumefaciens-mediated genetic transformation of graminaceous crops.

PubMed

Singh, Roshan Kumar; Prasad, Manoj

2016-05-01

Steady increase in global population poses several challenges to plant science research, including demand for increased crop productivity, grain yield, nutritional quality and improved tolerance to different environmental factors. Transgene-based approaches are promising to address these challenges by transferring potential candidate genes to host organisms through different strategies. Agrobacterium-mediated gene transfer is one such strategy which is well known for enabling efficient gene transfer in both monocot and dicots. Due to its versatility, this technique underwent several advancements including development of improved in vitro plant regeneration system, co-cultivation and selection methods, and use of hyper-virulent strains of Agrobacterium tumefaciens harbouring super-binary vectors. The efficiency of this method has also been enhanced by the use of acetosyringone to induce the activity of vir genes, silver nitrate to reduce the Agrobacterium-induced necrosis and cysteine to avoid callus browning during co-cultivation. In the last two decades, extensive efforts have been invested towards achieving efficient Agrobacterium-mediated transformation in cereals. Though high-efficiency transformation systems have been developed for rice and maize, comparatively lesser progress has been reported in other graminaceous crops. In this context, the present review discusses the progress made in Agrobacterium-mediated transformation system in rice, maize, wheat, barley, sorghum, sugarcane, Brachypodium, millets, bioenergy and forage and turf grasses. In addition, it also provides an overview of the genes that have been recently transferred to these graminaceous crops using Agrobacterium, bottlenecks in this technique and future possibilities for crop improvement.

Making Progress: The Use of Multiple Progress Reports to Enhance Advertising Students' Media Plan Term Projects

ERIC Educational Resources Information Center

Kritz, Gary H.; Lozada, Hector R.; Long, Mary M.

2007-01-01

Since the AACSB mandates that students demonstrate effective oral and written communication skills, it is imperative that business professors do what is necessary to improve such skills. The authors investigate whether the use of using multiple progress reports in an Advertising class project improves the final product. The data results show that…

Effect of Single-Sex Education on Progress in GCSE

ERIC Educational Resources Information Center

Malacova, Eva

2007-01-01

Multilevel modeling was carried out on national value-added data to study the effects of single-sex education on the progress of pupils from 2002 Key Stage 3 to 2004 GCSE. The analysis suggests that pupils in a selective environment achieve higher progress in single-sex schools; however, the advantage of single-sex schooling seems to decrease with…

Impact of the Level of State Tax Code Progressivity on Children's Health Outcomes

ERIC Educational Resources Information Center

Granruth, Laura Brierton; Shields, Joseph J.

2011-01-01

This research study examines the impact of the level of state tax code progressivity on selected children's health outcomes. Specifically, it examines the degree to which a state's tax code ranking along the progressive-regressive continuum relates to percentage of low birthweight babies, infant and child mortality rates, and percentage of…

Adventures in hepatocarcinogenesis.

PubMed

Pitot, Henry C

2007-01-01

Neoplasia is a heritably altered, relatively autonomous growth of tissue. Hepatocarcinogenesis, the pathogenesis of neoplasia in liver, as modeled in the rat exhibits three distinct, quantifiable stages: initiation, promotion, and progression. Simple mutations and/or epigenetic alterations may result in the irreversible stage of initiation. The stage of promotion results from selective enhancement of cell replication and selective inhibition of cellular apoptosis of initiated cells dependent on the genetic and/or epigenetic alterations of the latter. The irreversible stage of progression results from initial karyotypic alterations that evolve into greater degrees of genomic instability. The initial genomic alteration in the transition from promotion to progression may involve primarily epigenetic mechanisms driven by epigenetic and genetic alterations fixed during the stage of promotion.

Ovine progressive pneumonia provirus levels are unaffected by the prion 171R allele in an Idaho sheep flock.

PubMed

Harrington, Robert D; Herrmann-Hoesing, Lynn M; White, Stephen N; O'Rourke, Katherine I; Knowles, Donald P

2009-01-22

Selective breeding of sheep for arginine (R) at prion gene (PRNP) codon 171 confers resistance to classical scrapie. However, other effects of 171R selection are uncertain. Ovine progressive pneumonia/Maedi-Visna virus (OPPV) may infect up to 66% of a flock thus any affect of 171R selection on OPPV susceptibility or disease progression could have major impact on the sheep industry. Hypotheses that the PRNP 171R allele is 1) associated with the presence of OPPV provirus and 2) associated with higher provirus levels were tested in an Idaho ewe flock. OPPV provirus was found in 226 of 358 ewes by quantitative PCR. The frequency of ewes with detectable provirus did not differ significantly among the 171QQ, 171QR, and 171RR genotypes (p > 0.05). Also, OPPV provirus levels in infected ewes were not significantly different among codon 171 genotypes (p > 0.05). These results show that, in the flock examined, the presence of OPPV provirus and provirus levels are not related to the PRNP 171R allele. Therefore, a genetic approach to scrapie control is not expected to increase or decrease the number of OPPV infected sheep or the progression of disease. This study provides further support to the adoption of PRNP 171R selection as a scrapie control measure.

Longitudinal effects of a collegiate strength and conditioning program in American football.

PubMed

Stodden, David F; Galitski, Hayes M

2010-09-01

The purpose of this study was to examine the longitudinal effects of a strength and conditioning program on selected body composition and performance data over 4 consecutive years of training. Body mass, percent body fat, lean body mass, proagility (18.3 m shuttle), 36.6-m (40-yd) sprint, bench press, chin-ups, vertical jump, and power index data for 84 National Collegiate Athletic Association division IA collegiate football players were examined. In addition to examining data on all athletes, data were analyzed on specific groups categorized by position. Groups were categorized as (a) skill (wide receivers, defensive backs, and running backs), (b) big skill (linebackers, kickers, tight ends, quarterbacks, and specialists), and (c) line (offensive and defensive linemen). Data on each individual performance criteria were analyzed using pairwise t-tests to indicate changes from year to year. Results for all participants showed that the greatest number of significant improvements among test parameters occurred during the first year of training. Years 2-4 of training demonstrated inconsistent improvement among the test parameters. Bench press performance significantly improved throughout 4 years of training among all participants. Data analysis from specific position groups also revealed the greatest number of significant improvements occurred during the first year of training. Overall, the results of this study clearly demonstrate that the greatest rate of improvement in the selected performance parameters occurred during the initial year of the strength and conditioning program. This study provides valuable information for coaches to establish appropriate progression and program variation guidelines for athletes over consecutive years of training.

Tumor heterogeneity and resistance to EGFR-targeted therapy in advanced nonsmall cell lung cancer: challenges and perspectives

PubMed Central

Cheng, Xinghua; Chen, Haiquan

2014-01-01

Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed. PMID:25285017

Investigating the mental abilities of rural Zulu primary school children in South Africa.

PubMed

Jinabhai, C C; Taylor, M; Rangongo, M F; Mkhize, N J; Anderson, S; Pillay, B J; Sullivan, K R

2004-02-01

Maximising the full potential of health and educational interventions in South African schools requires assessment of the current level of mental abilities of the school children as measured by cognitive and scholastic tests and the identification of any barriers to improved performance. This study reports on the application and interpretation of a selected battery of mental ability tests among Zulu school children and the methodological and analytical issues that need to be addressed. The test scores of 806 primary school children from a rural community are presented, based on four tests: Raven's Coloured Progressive Matrices (CPM), an Auditory Verbal Learning Test (AVLT), the Symbol Digit Modalities Test (SDMT) and Young's Group Mathematics Test (GMT). Significant gender differences were found in the test scores, and the mean scores of Zulu children in this study were lower than those reported in other studies. The results of this selected test battery provide data for the further development of appropriate test instruments for South African conditions. These results can contribute towards the development of a test battery for South African children that can be used to assess and improve their school performance.

How Darwinian is cultural evolution?

PubMed Central

Claidière, Nicolas; Scott-Phillips, Thomas C.; Sperber, Dan

2014-01-01

Darwin-inspired population thinking suggests approaching culture as a population of items of different types, whose relative frequencies may change over time. Three nested subtypes of populational models can be distinguished: evolutionary, selectional and replicative. Substantial progress has been made in the study of cultural evolution by modelling it within the selectional frame. This progress has involved idealizing away from phenomena that may be critical to an adequate understanding of culture and cultural evolution, particularly the constructive aspect of the mechanisms of cultural transmission. Taking these aspects into account, we describe cultural evolution in terms of cultural attraction, which is populational and evolutionary, but only selectional under certain circumstances. As such, in order to model cultural evolution, we must not simply adjust existing replicative or selectional models but we should rather generalize them, so that, just as replicator-based selection is one form that Darwinian selection can take, selection itself is one of several different forms that attraction can take. We present an elementary formalization of the idea of cultural attraction. PMID:24686939

How Darwinian is cultural evolution?

PubMed

Claidière, Nicolas; Scott-Phillips, Thomas C; Sperber, Dan

2014-05-19

Darwin-inspired population thinking suggests approaching culture as a population of items of different types, whose relative frequencies may change over time. Three nested subtypes of populational models can be distinguished: evolutionary, selectional and replicative. Substantial progress has been made in the study of cultural evolution by modelling it within the selectional frame. This progress has involved idealizing away from phenomena that may be critical to an adequate understanding of culture and cultural evolution, particularly the constructive aspect of the mechanisms of cultural transmission. Taking these aspects into account, we describe cultural evolution in terms of cultural attraction, which is populational and evolutionary, but only selectional under certain circumstances. As such, in order to model cultural evolution, we must not simply adjust existing replicative or selectional models but we should rather generalize them, so that, just as replicator-based selection is one form that Darwinian selection can take, selection itself is one of several different forms that attraction can take. We present an elementary formalization of the idea of cultural attraction.

Lumbar Spinal Stenosis Minimally Invasive Treatment with Bilateral Transpedicular Facet Augmentation System

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

Masala, Salvatore, E-mail: salva.masala@tiscali.it; Tarantino, Umberto; Nano, Giovanni, E-mail: gionano@gmail.com

Purpose. The purpose of this study was to evaluate the effectiveness of a new pedicle screw-based posterior dynamic stabilization device PDS Percudyn System Trade-Mark-Sign Anchor and Stabilizer (Interventional Spine Inc., Irvine, CA) as alternative minimally invasive treatment for patients with lumbar spine stenosis. Methods. Twenty-four consecutive patients (8 women, 16 men; mean age 61.8 yr) with lumbar spinal stenosis underwent implantation of the minimally invasive pedicle screw-based device for posterior dynamic stabilization. Inclusion criteria were lumbar stenosis without signs of instability, resistant to conservative treatment, and eligible to traditional surgical posterior decompression. Results. Twenty patients (83 %) progressively improved duringmore » the 1-year follow-up. Four (17 %) patients did not show any improvement and opted for surgical posterior decompression. For both responder and nonresponder patients, no device-related complications were reported. Conclusions. Minimally invasive PDS Percudyn System Trade-Mark-Sign has effectively improved the clinical setting of 83 % of highly selected patients treated, delaying the need for traditional surgical therapy.« less

Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery

PubMed Central

Yata, Teerapong; Lee, Koon-Yang; Dharakul, Tararaj; Songsivilai, Sirirurg; Bismarck, Alexander; Mintz, Paul J; Hajitou, Amin

2014-01-01

Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage), viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage. PMID:25118171

Emerging engineering principles for yield improvement in microbial cell design.

PubMed

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling.

Emerging engineering principles for yield improvement in microbial cell design

PubMed Central

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling. PMID:24688676

Neural correlates underlying micrographia in Parkinson’s disease

PubMed Central

Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

2016-01-01

Micrographia is a common symptom in Parkinson’s disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

The introduction of new policies and strategies to reduce inequities and improve child health in Kenya: A country case study on progress in child survival, 2000-2013.

PubMed

Brault, Marie A; Ngure, Kenneth; Haley, Connie A; Kabaka, Stewart; Sergon, Kibet; Desta, Teshome; Mwinga, Kasonde; Vermund, Sten H; Kipp, Aaron M

2017-01-01

As of 2015, only 12 countries in the World Health Organization's AFRO region had met Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across the African region, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Kenya was one of the countries selected for an in-depth case study due to its insufficient progress in reducing under-five mortality, with only a 28% reduction between 1990 and 2013. This paper presents indicators, national documents, and qualitative data describing the factors that have both facilitated and hindered Kenya's efforts in reducing child mortality. Key barriers identified in the data were widespread socioeconomic and geographic inequities in access and utilization of maternal, neonatal, and child health (MNCH) care. To reduce these inequities, Kenya implemented three major policies/strategies during the study period: removal of user fees, the Kenya Essential Package for Health, and the Community Health Strategy. This paper uses qualitative data and a policy review to explore the early impacts of these efforts. The removal of user fees has been unevenly implemented as patients still face hidden expenses. The Kenya Essential Package for Health has enabled construction and/or expansion of healthcare facilities in many areas, but facilities struggle to provide Emergency Obstetric and Neonatal Care (EmONC), neonatal care, and many essential medicines and commodities. The Community Health Strategy appears to have had the most impact, improving referrals from the community and provision of immunizations, malaria prevention, and Prevention of Mother-to-Child Transmission of HIV. However, the Community Health Strategy is limited by resources and thus also unevenly implemented in many areas. Although insufficient progress was made pre-2015, with additional resources and further scale-up of new policies and strategies Kenya can make further progress in child survival.

The introduction of new policies and strategies to reduce inequities and improve child health in Kenya: A country case study on progress in child survival, 2000-2013

PubMed Central

Brault, Marie A.; Ngure, Kenneth; Haley, Connie A.; Kabaka, Stewart; Sergon, Kibet; Desta, Teshome; Mwinga, Kasonde; Vermund, Sten H.; Kipp, Aaron M.

2017-01-01

As of 2015, only 12 countries in the World Health Organization’s AFRO region had met Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across the African region, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Kenya was one of the countries selected for an in-depth case study due to its insufficient progress in reducing under-five mortality, with only a 28% reduction between 1990 and 2013. This paper presents indicators, national documents, and qualitative data describing the factors that have both facilitated and hindered Kenya’s efforts in reducing child mortality. Key barriers identified in the data were widespread socioeconomic and geographic inequities in access and utilization of maternal, neonatal, and child health (MNCH) care. To reduce these inequities, Kenya implemented three major policies/strategies during the study period: removal of user fees, the Kenya Essential Package for Health, and the Community Health Strategy. This paper uses qualitative data and a policy review to explore the early impacts of these efforts. The removal of user fees has been unevenly implemented as patients still face hidden expenses. The Kenya Essential Package for Health has enabled construction and/or expansion of healthcare facilities in many areas, but facilities struggle to provide Emergency Obstetric and Neonatal Care (EmONC), neonatal care, and many essential medicines and commodities. The Community Health Strategy appears to have had the most impact, improving referrals from the community and provision of immunizations, malaria prevention, and Prevention of Mother-to-Child Transmission of HIV. However, the Community Health Strategy is limited by resources and thus also unevenly implemented in many areas. Although insufficient progress was made pre-2015, with additional resources and further scale-up of new policies and strategies Kenya can make further progress in child survival. PMID:28763454

Molecularly imprinted polymers for sample preparation and biosensing in food analysis: Progress and perspectives.

PubMed

Ashley, Jon; Shahbazi, Mohammad-Ali; Kant, Krishna; Chidambara, Vinayaka Aaydha; Wolff, Anders; Bang, Dang Duong; Sun, Yi

2017-05-15

Molecularly imprinted polymers (MIPs) are biomimetics which can selectively bind to analytes of interest. One of the most interesting areas where MIPs have shown the biggest potential is food analysis. MIPs have found use as sorbents in sample preparation attributed to the high selectivity and high loading capacity. MIPs have been intensively employed in classical solid-phase extraction and solid-phase microextraction. More recently, MIPs have been combined with magnetic bead extraction, which greatly simplifies sample handling procedures. Studies have consistently shown that MIPs can effectively minimize complex food matrix effects, and improve recoveries and detection limits. In addition to sample preparation, MIPs have also been viewed as promising alternatives to bio-receptors due to the inherent molecular recognition abilities and the high stability in harsh chemical and physical conditions. MIPs have been utilized as receptors in biosensing platforms such as electrochemical, optical and mass biosensors to detect various analytes in food. In this review, we will discuss the current state-of-the-art of MIP synthesis and applications in the context of food analysis. We will highlight the imprinting methods which are applicable for imprinting food templates, summarize the recent progress in using MIPs for preparing and analysing food samples, and discuss the current limitations in the commercialisation of MIPs technology. Finally, future perspectives will be given. Copyright © 2017 Elsevier B.V. All rights reserved.

A Framework for the Initiation of Networked Improvement Communities

ERIC Educational Resources Information Center

Russell, Jennifer Lin; Bryk, Anthony S.; Dolle, Jonathan R.; Gomez, Louis M.; Lemahieu, Paul G.; Grunow, Alicia

2017-01-01

Background/Context: Educators around the country are working individually and collectively to improve teaching and learning. Despite marked progress in some places driven by these improvement efforts, overall progress in the education field has been slow and outcomes remain highly variable. This is partly because the field is not organized to…

Progressive Consent and Specimen Accrual Models to Address Sustainability: A Decade's Experience at an Oregon Biorepository.

PubMed

Ost, John A; Newton, Paul W; Neilson, Duncan R; Cioffi, Joseph A; Wackym, P Ashley; Perkins, R Serene

2017-02-01

The Legacy Biorepository is a College of American Pathologists-accredited biorepository operating within a seven-hospital healthcare system, with a decade's experience in specimen accrual, storage, and distribution. While standardization of our practices through accreditation remains a priority, we along with others face challenges with regard to sustainability. Purposeful changes in our consent process, which we term "progressive consent," are expected to improve sustainability and operational flexibility while increasing our scientific impact. Until 2015, informed consent was performed primarily by biorepository staff at an estimated time of 1 hour per case. After a process improvement exercise, we successfully changed our informed consent process to a modified front-door model, with use of material and data for research as an opt-in or opt-out selection on the institutional patient informed consent form provided to surgery patients in the healthcare system. Successful implementation of this change required the engagement and participation of multiple stakeholders in healthcare system leadership, hospital administration, research, legal, regulatory, and patient care levels. A modified front-door consent enabled us to collect an additional 38 specimens in the first two quarters of 2016, with a time commitment of 15.75 hours, a time savings per specimen increasing in Q2 over Q1. We estimate a potential savings of 43 hours in 2016. This progressive model allowed us to maintain our frozen sample collection while increasing the availability of paraffin-embedded tissue and bodily fluids. Augmenting our tissue collection added little expense per case (approximately half that of each frozen tissue aliquot) and increased the range of biospecimens collected. Biorepository financial sustainability is a critical issue. Thorough evaluation and modification of existing procedures and collection models, as well as cost recovery initiatives, can translate into savings. Sustainability, process improvement, and scientific impact broadly overlap and continue to require operational critique and implementation of strategic changes.

CNS drug development in Europe--past progress and future challenges.

PubMed

Nutt, David J; Attridge, Jim

2014-01-01

Despite enormous progress in defining, diagnosing and treating mental disorders, EU health systems face a mounting challenge in responding to 'unmet need'. Mental illnesses produce a societal burden that exceeds that for either cancers or cardiovascular conditions. Leveraging advances in science and medicine to make available new innovative medicines is a key component in responding to this challenge. The dominant paradigm has been, is and will continue to be, one of incremental progress. Better medicines for depression, anxiety and psychoses in the working age population would add great value to patients and improve labour productivity. But psychotropic medicines face exceptional challenges in demonstrating their added value, due to uncertainty in patient diagnosis, selecting treatments and ensuring adherence. Also, there are major difficulties in estimating costs. Advances in understanding brain processes, identifying biomarkers and neuro-imaging techniques promise far more effective 'diagnostic-therapeutic' treatments and improved patient outcomes in the future. Currently there are valuable incremental innovations in late development, which may well fail to recover their R&D costs, because of very low reimbursed prices. This will send a signal to innovators not to persist with product development in this area. Recently several leading companies have withdrawn from R&D in these mental disorders. This is a worrying development since building the capabilities to succeed in any disease sector takes many years and, once dismantled, they cannot easily be re-established. Three policy interventions could improve innovation incentives: Further 'push' incentives under i) and streamlining under ii) alone will not reverse the decline in investment incentives. An EU consensus, based upon an innovation model which encompasses the Research, Development and Market phases as a single cyclical process, which addresses the weak 'market pull incentives' under iii) is needed. There is a very real risk that without such an integrated approach to policy reforms, innovation in psychotropic medicines will become a 'desert' in the same way that it did for antibiotics in the 1990's. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic variation assessed with microsatellites in mass selection lines of the Pacific oyster ( Crassostrea gigas) in China

NASA Astrophysics Data System (ADS)

Wang, Xubo; Li, Qi; Yu, Hong; Kong, Lingfeng

2016-12-01

Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding programs in China were examined at ten polymorphic microsatellite loci to assess the level of allelic diversity and estimate the effective population size. These data were compared with those of their base population. The results showed that the genetic variation of the four generations were maintained at high levels with an average allelic richness of 18.8-20.6, and a mean expected heterozygosity of 0.902-0.921. They were not reduced compared with those of their base population. Estimated effective population sizes based on temporal variances in microsatellite frequencies were smaller to that of sex ratio-corrected broodstock count estimates. Using a relatively large number of broodstock and keeping an equal sex ratio in the broodstock each generation may have contributed to retaining the original genetic diversity and maintaining relatively large effective population size. The results obtained in this study showed that the genetic variation was not affected greatly by mass selection progress and high genetic variation still existed in the mass selection lines, suggesting that there is still potential for increasing the gains in future generations of C. gigas. The present study provided important information for future genetic improvement by selective breeding, and for the design of suitable management guidelines for genetic breeding of C. gigas.

When do changes in cancer survival mean progress? The insight from population incidence and mortality.

PubMed

Cho, Hyunsoon; Mariotto, Angela B; Schwartz, Lisa M; Luo, Jun; Woloshin, Steven

2014-11-01

It is often assumed that increases in cancer survival reflect true progress against cancer. This is true when these increases are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from cancer (ie, decreased incidence and mortality). But increased survival can also occur even when incidence is increasing and mortality is unchanged. To use trends in cancer burden-incidence and mortality-to illustrate when changes in survival reflect true progress. Using data from 1975 to 2010 collected by the Surveillance, Epidemiology, and End Results Program (incidence, survival) and the National Center for Health Statistics (mortality), we analyzed US trends in five-year relative survival, age-adjusted incidence, and mortality for selected cancers to identify patterns that do and do not reflect progress. Among the nine common cancers examined, survival increased in seven, and changed little or not at all for two. In some cases, increased survival was accompanied by decreased burden of disease, reflecting true progress. For example, from 1975 to 2010, five-year survival for colon cancer patients improved (from 48% to 68%) while cancer burden fell: Fewer cases (incidence decreased from 60 to 41 per 100,000) and fewer deaths (mortality decreased from 28 to 16 per 100,000), a pattern explained by both increased early detection (with removal of cancer precursors) and more effective treatment. In other cases, however, increased survival did not reflect true progress. In melanoma, kidney, and thyroid cancer, five-year survival increased but incidence increased with no change in mortality. This pattern suggests overdiagnosis from increased early detection, an increase in cancer burden. Changes in survival must be interpreted in the context of incidence and mortality. Increased survival only represents progress when accompanied by a reduction in incidence, mortality, or ideally both. Published by Oxford University Press 2014.

When Do Changes in Cancer Survival Mean Progress? The Insight From Population Incidence and Mortality

PubMed Central

Mariotto, Angela B.; Schwartz, Lisa M.; Luo, Jun; Woloshin, Steven

2014-01-01

Background It is often assumed that increases in cancer survival reflect true progress against cancer. This is true when these increases are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from cancer (ie, decreased incidence and mortality). But increased survival can also occur even when incidence is increasing and mortality is unchanged. Objective To use trends in cancer burden—incidence and mortality—to illustrate when changes in survival reflect true progress. Methods Using data from 1975 to 2010 collected by the Surveillance, Epidemiology, and End Results Program (incidence, survival) and the National Center for Health Statistics (mortality), we analyzed US trends in five-year relative survival, age-adjusted incidence, and mortality for selected cancers to identify patterns that do and do not reflect progress. Results Among the nine common cancers examined, survival increased in seven, and changed little or not at all for two. In some cases, increased survival was accompanied by decreased burden of disease, reflecting true progress. For example, from 1975 to 2010, five-year survival for colon cancer patients improved (from 48% to 68%) while cancer burden fell: Fewer cases (incidence decreased from 60 to 41 per 100000) and fewer deaths (mortality decreased from 28 to 16 per 100000), a pattern explained by both increased early detection (with removal of cancer precursors) and more effective treatment. In other cases, however, increased survival did not reflect true progress. In melanoma, kidney, and thyroid cancer, five-year survival increased but incidence increased with no change in mortality. This pattern suggests overdiagnosis from increased early detection, an increase in cancer burden. Conclusions Changes in survival must be interpreted in the context of incidence and mortality. Increased survival only represents progress when accompanied by a reduction in incidence, mortality, or ideally both. PMID:25417232

Photophysics and Photochemistry

ERIC Educational Resources Information Center

Letokhov, V. S.

1977-01-01

Discusses recent progress in using tunable lasers to selectively separate substances at the atomic and molecular level. Emphasizes biological applications, such as selective excitation and breaking of hydrogen bonds in DNA. (MLH)

Progress in Organization Development Research.

ERIC Educational Resources Information Center

Roberts, Nancy C.; Porras, Jerry I.

1982-01-01

Describes major areas of progress in organization development (OD): progress in operationalizing the concept of change; progress in improving measurement; and progress in designing statistical procedures used to analyze OD intervention data. Suggests recent research developments point to a more solid base on which to build OD practice and theory.…

Colloid centrifugation of boar semen.

PubMed

Morrell, J M; Wallgren, M

2011-09-01

Colloid centrifugation of boar semen has been reported sporadically for at least the last two decades, beginning with density gradient centrifugation (DGC) and progressing more recently to single layer centrifugation (SLC). Single layer centrifugation through a species-specific colloid has been shown to be effective in selecting the best spermatozoa (spermatozoa with good motility and normal morphology) from boar sperm samples. The method is easier to use and less time-consuming than DGC and has been scaled-up to allow whole ejaculates from other species, e.g. stallions, to be processed in a practical manner. The SLC technique is described, and various scale-up versions are presented. The potential applications for SLC in boar semen preservation are as follows: to improve sperm quality in artificial insemination (AI) doses for 'problem' boars; to increase the shelf-life of normal stored sperm samples, either by processing the fresh semen before preparing AI doses or by processing the stored semen dose to extract the best spermatozoa; to remove pathogens (viruses, bacteria), thus improving biosecurity of semen doses and potentially reducing the use of antibiotics; to improve cryosurvival by removing dead and dying spermatozoa prior to cryopreservation; to select spermatozoa for in vitro fertilization. These applications are discussed and practical examples are provided. Finally, a few thoughts about the economic value of the technique to the boar semen industry are presented. © 2011 Blackwell Verlag GmbH.

Improving Multi-Functional Properties in Polymer Based Nano Composites by Interfacial

NASA Astrophysics Data System (ADS)

Tajaddod, Navid

Polymer nanocomposites (PNCs) have become an area of increasing interest for study in the field of polymer science and technology since the rise of nanotechnology research. Despite the significant amount of progress being made towards producing high quality PNC materials, improvement in the mechanical, electrical, thermal and other functional properties still remain a challenge. To date, these properties are only a fraction of the expected theoretical values predicted for these materials. Development of interfacial regions between the filler and matrix within the composite has been found to be an important focus in terms of processing. Proper interfacial control and development may ensure excellent interaction and property transfer between the filler and polymer matrix in addition to improvement of multi-functional properties of PNCs. The property-structure importance for the existence of the interfacial and interphase region within PNCs is discussed in this thesis work. Two specific PNC systems are selected for study as part of this dissertation in order to understand the effect of interfacial region development on influencing multi-functional property trends. Polyethylene (PE)/boron nitride (BN) and polyacrylonitrile (PAN)/carbon nanotube (CNT) composites were selected to investigate their mechanical performance and thermal and electrical conductivity properties, respectively. For these systems it was found that the interfacial region structure is directly related to the enhancement of the subsequent multi-functional properties.

Developmental Pathways Are Blueprints for Designing Successful Crops

PubMed Central

Trevaskis, Ben

2018-01-01

Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene–gene or gene–environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted. PMID:29922318

Developmental Pathways Are Blueprints for Designing Successful Crops.

PubMed

Trevaskis, Ben

2018-01-01

Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene-gene or gene-environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted.

From Travis to Today: An Analysis Of Racial Progress in the Us Air Force Officer Corps Since 1971

DTIC Science & Technology

2009-04-01

Over Who Have Completed High School or College, by Race, Hispanic Origin and Sex : Selected Years 1940 to 2007,” http://www.census.gov/population/www...and Over Who Have Completed High School or College, by Race, Hispanic Origin and Sex : Selected Years 1940 to 2007,” http://www.census.gov/population...of Defense, Career Progression of Minority and Women Officers, ix. 38 Dorn, Edwin, Who Defends America? Race, Sex , and Class in the Armed Forces

The application of artificial intelligence to microarray data: identification of a novel gene signature to identify bladder cancer progression.

PubMed

Catto, James W F; Abbod, Maysam F; Wild, Peter J; Linkens, Derek A; Pilarsky, Christian; Rehman, Ishtiaq; Rosario, Derek J; Denzinger, Stefan; Burger, Maximilian; Stoehr, Robert; Knuechel, Ruth; Hartmann, Arndt; Hamdy, Freddie C

2010-03-01

New methods for identifying bladder cancer (BCa) progression are required. Gene expression microarrays can reveal insights into disease biology and identify novel biomarkers. However, these experiments produce large datasets that are difficult to interpret. To develop a novel method of microarray analysis combining two forms of artificial intelligence (AI): neurofuzzy modelling (NFM) and artificial neural networks (ANN) and validate it in a BCa cohort. We used AI and statistical analyses to identify progression-related genes in a microarray dataset (n=66 tumours, n=2800 genes). The AI-selected genes were then investigated in a second cohort (n=262 tumours) using immunohistochemistry. We compared the accuracy of AI and statistical approaches to identify tumour progression. AI identified 11 progression-associated genes (odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.56-0.87; p=0.0004), and these were more discriminate than genes chosen using statistical analyses (OR: 1.24; 95% CI, 0.96-1.60; p=0.09). The expression of six AI-selected genes (LIG3, FAS, KRT18, ICAM1, DSG2, and BRCA2) was determined using commercial antibodies and successfully identified tumour progression (concordance index: 0.66; log-rank test: p=0.01). AI-selected genes were more discriminate than pathologic criteria at determining progression (Cox multivariate analysis: p=0.01). Limitations include the use of statistical correlation to identify 200 genes for AI analysis and that we did not compare regression identified genes with immunohistochemistry. AI and statistical analyses use different techniques of inference to determine gene-phenotype associations and identify distinct prognostic gene signatures that are equally valid. We have identified a prognostic gene signature whose members reflect a variety of carcinogenic pathways that could identify progression in non-muscle-invasive BCa. 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Commercial Sensory Survey Radiation Testing Progress Report

NASA Technical Reports Server (NTRS)

Becker, Heidi N.; Dolphic, Michael D.; Thorbourn, Dennis O.; Alexander, James W.; Salomon, Phil M.

2008-01-01

The NASA Electronic Parts and Packaging (NEPP) Program Sensor Technology Commercial Sensor Survey task is geared toward benefiting future NASA space missions with low-cost, short-duty-cycle, visible imaging needs. Such applications could include imaging for educational outreach purposes or short surveys of spacecraft, planetary, or lunar surfaces. Under the task, inexpensive commercial grade CMOS sensors were surveyed in fiscal year 2007 (FY07) and three sensors were selected for total ionizing dose (TID) and displacement damage dose (DDD) tolerance testing. The selected sensors had to meet selection criteria chosen to support small, low-mass cameras that produce good resolution color images. These criteria are discussed in detail in [1]. This document discusses the progress of radiation testing on the Micron and OmniVision sensors selected in FY07 for radiation tolerance testing.

System and method for progressive band selection for hyperspectral images

NASA Technical Reports Server (NTRS)

Fisher, Kevin (Inventor)

2013-01-01

Disclosed herein are systems, methods, and non-transitory computer-readable storage media for progressive band selection for hyperspectral images. A system having module configured to control a processor to practice the method calculates a virtual dimensionality of a hyperspectral image having multiple bands to determine a quantity Q of how many bands are needed for a threshold level of information, ranks each band based on a statistical measure, selects Q bands from the multiple bands to generate a subset of bands based on the virtual dimensionality, and generates a reduced image based on the subset of bands. This approach can create reduced datasets of full hyperspectral images tailored for individual applications. The system uses a metric specific to a target application to rank the image bands, and then selects the most useful bands. The number of bands selected can be specified manually or calculated from the hyperspectral image's virtual dimensionality.

A novel evaluation method for building construction project based on integrated information entropy with reliability theory.

PubMed

Bai, Xiao-ping; Zhang, Xi-wei

2013-01-01

Selecting construction schemes of the building engineering project is a complex multiobjective optimization decision process, in which many indexes need to be selected to find the optimum scheme. Aiming at this problem, this paper selects cost, progress, quality, and safety as the four first-order evaluation indexes, uses the quantitative method for the cost index, uses integrated qualitative and quantitative methodologies for progress, quality, and safety indexes, and integrates engineering economics, reliability theories, and information entropy theory to present a new evaluation method for building construction project. Combined with a practical case, this paper also presents detailed computing processes and steps, including selecting all order indexes, establishing the index matrix, computing score values of all order indexes, computing the synthesis score, sorting all selected schemes, and making analysis and decision. Presented method can offer valuable references for risk computing of building construction projects.

Progressive resistance strength training for improving physical function in older adults

PubMed Central

Liu, Chiung-ju; Latham, Nancy K

2014-01-01

Background Muscle weakness in old age is associated with physical function decline. Progressive resistance strength training (PRT) exercises are designed to increase strength. Objectives To assess the effects of PRT on older people and identify adverse events. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 01, 2008), EMBASE (1980 to February 06 2007), CINAHL (1982 to July 01 2007) and two other electronic databases. We also searched reference lists of articles, reviewed conference abstracts and contacted authors. Selection criteria Randomised controlled trials reporting physical outcomes of PRT for older people were included. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted data. Data were pooled where appropriate. Main results One hundred and twenty one trials with 6700 participants were included. In most trials, PRT was performed two to three times per week and at a high intensity. PRT resulted in a small but significant improvement in physical ability (33 trials, 2172 participants; SMD 0.14, 95% CI 0.05 to 0.22). Functional limitation measures also showed improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179 participants, MD 0.08 m/s, 95% CI 0.04 to 0.12); and a moderate to large effect for getting out of a chair (11 trials, 384 participants, SMD -0.94, 95% CI -1.49 to -0.38). PRT had a large positive effect on muscle strength (73 trials, 3059 participants, SMD 0.84, 95% CI 0.67 to 1.00). Participants with osteoarthritis reported a reduction in pain following PRT (6 trials, 503 participants, SMD -0.30, 95% CI -0.48 to -0.13). There was no evidence from 10 other trials (587 participants) that PRT had an effect on bodily pain. Adverse events were poorly recorded but adverse events related to musculoskeletal complaints, such as joint pain and muscle soreness, were reported in many of the studies that prospectively defined and monitored these events. Serious adverse events were rare, and no serious events were reported to be directly related to the exercise programme. Authors' conclusions This review provides evidence that PRT is an effective intervention for improving physical functioning in older people, including improving strength and the performance of some simple and complex activities. However, some caution is needed with transferring these exercises for use with clinical populations because adverse events are not adequately reported. PMID:19588334

Recent progress and considerations for AAV gene therapies targeting the central nervous system.

PubMed

Lykken, Erik Allen; Shyng, Charles; Edwards, Reginald James; Rozenberg, Alejandra; Gray, Steven James

2018-05-18

Neurodevelopmental disorders, as a class of diseases, have been particularly difficult to treat even when the underlying cause(s), such as genetic alterations, are understood. What treatments do exist are generally not curative and instead seek to improve quality of life for affected individuals. The advent of gene therapy via gene replacement offers the potential for transformative therapies to slow or even stop disease progression for current patients and perhaps minimize or prevent the appearance of symptoms in future patients. This review focuses on adeno-associated virus (AAV) gene therapies for diseases of the central nervous system. An overview of advances in AAV vector design for therapy is provided, along with a description of current strategies to develop AAV vectors with tailored tropism. Next, progress towards treatment of neurodegenerative diseases is presented at both the pre-clinical and clinical stages, focusing on a few select diseases to highlight broad categories of therapeutic parameters. Special considerations for more challenging cases are then discussed in addition to the immunological aspects of gene therapy. With the promising clinical trial results that have been observed for the latest AAV gene therapies and continued pre-clinical successes, the question is no longer whether a therapy can be developed for certain neurodevelopmental disorders, but rather, how quickly.

Tissue Engineering and Regenerative Medicine 2017: A Year in Review.

PubMed

Park, Kyung Min; Shin, Young Min; Kim, Kyobum; Shin, Heungsoo

2018-04-26

In 2017, a new paradigm change caused by artificial intelligence and big data analysis resulted in innovation in each field of science and technology, and also significantly influenced progress in tissue engineering and regenerative medicine (TERM). TERM has continued to make technological advances based on interdisciplinary approaches and has contributed to the overall field of biomedical technology, including cancer biology, personalized medicine, development biology, and cell-based therapeutics. While researchers are aware that there is still a long way to go until TERM reaches the ultimate goal of patient treatment through clinical translation, the rapid progress in convergence studies led by technological improvements in TERM has been encouraging. In this review, we highlighted the significant advances made in TERM in 2017 (with an overlap of 5 months in 2016). We identified major progress in TERM in a manner similar to previous reviews published in the last few years. In addition, we carefully considered all four previous reviews during the selection process and chose main themes that minimize the duplication of the topics. Therefore, we have identified three areas that have been the focus of most journal publications in the TERM community in 2017: (i) advanced biomaterials and three-dimensional (3D) cell printing, (ii) exosomes as bioactive agents for regenerative medicine, and (iii) 3D culture in regenerative medicine.

Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations

PubMed Central

Wang, Jun; Wang, Baocheng; Chu, Huili; Yao, Yunfeng

2016-01-01

Identifying activating EGFR mutations is a useful predictive strategy that helps select a population of advanced non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors (TKIs). Patients with sensitizing EGFR mutations (predominantly an in-frame deletion in exon 19 and an L858R substitution) are highly responsive to first-generation EGFR TKIs, such as gefitinib and erlotinib, and show improved progression-free survival without serious side effects. However, all patients with activating EGFR mutations who are initially responsive to EGFR TKIs eventually develop acquired resistance after a median progression-free survival of 10–16 months, followed by disease progression. Moreover, ~20%–30% of NSCLC patients have no objective tumor regression on initial EGFR TKI treatment, although they harbor an activating EGFR mutation. These patients represent an NSCLC subgroup that is defined as having intrinsic or primary resistance to EGFR TKIs. Different mechanisms of acquired EGFR TKI resistance have been identified, and several novel compounds have been developed to reverse acquired resistance, but little is known about EGFR TKI intrinsic resistance. In this review, we summarize the latest findings involving mechanisms of intrinsic resistance to EGFR TKIs in advanced NSCLC with activating EGFR mutations and present possible therapeutic strategies to overcome this resistance. PMID:27382309

Health information technology and implementation science: partners in progress in the VHA.

PubMed

Hynes, Denise M; Whittier, Erika R; Owens, Arika

2013-03-01

The Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VA's electronic health record and information systems. To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VA QUERI program. Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. We conducted documentation analysis and semistructured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. : Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

PubMed

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PubMed

Wong, Lih-Ming; Toi, Ants; Van der Kwast, Theodorus; Trottier, Greg; Alibhai, Shabbir M H; Timilshina, Narhari; Evans, Andrew; Zlotta, Alexandre; Fleshner, Neil; Finelli, Antonio

2014-10-01

We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Morbidity of severe obesity.

PubMed

Kral, J G

2001-10-01

Although obesity is an easy diagnosis to make, its etiologies, pathophysiology, and symptomatology are extraordinarily complex. Progress in surgical technique and anesthesiological management has substantially improved the safety of performing operations on the severely obese in the last 20 years. These improvements have occurred more or less empirically, without a full understanding of etiology or pathophysiology, although this has advanced concomitantly with improvements in practice. This review has attempted to provide a framework to facilitate progress in the neglected areas of patient selection and choice of operation, in an effort to improve long-term outcome. Despite the disparate etiologies of obesity and its diverse comorbidities and complications, there are unifying interdependent pathogenetic mechanisms of great relevance to the practice of antiobesity surgery. The rate of eating, whether driven by HPA dysfunction, ambient stress, or related hereditary susceptibility factors including the increased energy demands of an expanded body fat mass, participates in a cycle that results in disordered satiety (see Fig. 3). This leads to substrate overload, causing extensive metabolic abnormalities such as atherogenesis, insulin resistance, thrombogenesis, and carcinogenesis. This interpretation of the pathophysiology of obesity ironically accords with the original meaning of the word obesity: "to overeat." The ultimate solution to the problem of obesity--preventing it--will not be forthcoming until the food industry is forced to lower production and change its marketing strategies, as the liquor and tobacco industries in the United States were compelled to do. This cannot occur until the large and fast-growing populations of industrialized nations become educated in the personal implications of the energy principle. Regardless of whether school curricula are modified to prioritize health education, the larger problems of cultural and economic change remain for the groups most susceptible to obesity. In this context, antiobesity surgery will continue to thrive, especially in the absence of effective alternatives.

Measuring quality progress

NASA Astrophysics Data System (ADS)

Lambert, Larry D.

The study by the American Productivity & Quality Center (APQC) was commissioned by Loral Space Information Systems, Inc. and the National Aeronautics and Space Administration (NASA) to evaluate internal assessment systems. APQC benchmarked approaches to the internal assessment of quality management systems in three phases. The first phase included work conducted for the International Benchmarking Clearinghouse (IBC) and consisted of an in-depth analysis of the 1991 Malcolm Baldrige National Quality Award criteria. The second phase was also performed for the IBC and compared the 1991 award criteria among the following quality awards: Deming Prize, Malcolm Baldrige National Quality Award, The President's Award for Quality and Productivity Improvement, The NASA Excellence Award (The George M. Lowe Trophy) for Quality and Productivity Improvement and the Shigeo Shingo Award for Excellence in Manufacturing. The third phase compared the internal implementation approaches of 23 companies selected from American industry for their recognized, formal assessment systems.

Measuring quality progress

NASA Technical Reports Server (NTRS)

Lambert, Larry D.

1992-01-01

The study by the American Productivity & Quality Center (APQC) was commissioned by Loral Space Information Systems, Inc. and the National Aeronautics and Space Administration (NASA) to evaluate internal assessment systems. APQC benchmarked approaches to the internal assessment of quality management systems in three phases. The first phase included work conducted for the International Benchmarking Clearinghouse (IBC) and consisted of an in-depth analysis of the 1991 Malcolm Baldrige National Quality Award criteria. The second phase was also performed for the IBC and compared the 1991 award criteria among the following quality awards: Deming Prize, Malcolm Baldrige National Quality Award, The President's Award for Quality and Productivity Improvement, The NASA Excellence Award (The George M. Lowe Trophy) for Quality and Productivity Improvement and the Shigeo Shingo Award for Excellence in Manufacturing. The third phase compared the internal implementation approaches of 23 companies selected from American industry for their recognized, formal assessment systems.

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

Testing of Synthetic Biological Membranes for Forward Osmosis Applications

NASA Technical Reports Server (NTRS)

Parodi, Jurek; Mangado, Jaione Romero; Stefanson, Ofir; Flynn, Michael; Mancinelli, Rocco; Kawashima, Brian; Trieu, Serena; Brozell, Adrian; Rosenberg, Kevan

2016-01-01

Commercially available forward osmosis membranes have been extensively tested for human space flight wastewater treatment. Despite the improvements achieved in the last decades, there is still a challenge to produce reliable membranes with anti-fouling properties, chemical resistance, and high flux and selectivity. Synthetic biological membranes that mimic the ones present in nature, which underwent millions of years of evolution, represent a potential solution for further development and progress in membrane technology. Biomimetic forward osmosis membranes based on a polymeric support filter and coated with surfactant multilayers have been engineered to investigate how different manufacturing processes impact the performance and structure of the membrane. However, initial results of the first generation prototype membranes tests reveal a high scatter in the data, due to the current testing apparatus set up. The testing apparatus has been upgraded to improve data collection, reduce errors, and to allow higher control of the testing process.

Advocacy for strengthening civil registration and vital statistics.

PubMed

Upham, Susan; Mikkelsen, Lene

2012-04-01

This article has presented the key elements of the advocacy process and the steps to consider in developing an advocacy campaign. There are compelling reasons for engaging in advocacy, particularly as civil registration systems in many countries have progressed very little over the past 50 years. Lack of awareness of the benefits for individuals and governments has contributed to a vicious cycle of under development of civil registration and vital statistics systems. Advocates are needed across a range of sectors to persuade governments to make CRVS a priority and to work towards a greater political commitment and allocation of resources for establishing and improving systems. Advocating for better legal frameworks and policies that fully support a functioning and well-used CRVS system is needed. A selection of tools and resources has been included in this module to get you started in advocating for improvements in your CRVS system. Box 4 summarises some key considerations when developing your advocacy campaign.

Long-term patency, pancreatic function, and pain relief after lateral pancreaticojejunostomy for chronic pancreatitis.

PubMed

Warshaw, A L; Popp, J W; Schapiro, R H

1980-08-01

Ten patients, all with intractable pain due to chronic pancreatitis, were selected for treatment by lateral pancreaticojejunostomy (modified Puestow procedure) after preoperative endoscopic pancreatography in each had revealed dilatation of the main pancreatic duct. Follow-up endoscopic pancreatograms performed 1 yr after surgery show a patent anastomosis in all 10 patients. Eight of these 10 are largely or completely pain-free, but 2 continiue to have pain without improvement after the operation. Surgical success in relieving pain was accompanied neither by improvement in pancreatic function, nor by protection against its further deterioration: Whereas 2 patients had malabsorption and 3 were diabetic preoperatively, 6 had malabsorption and 5 had diabetes postoperatively. This progression of exocrine or endorine pancreatic insufficiency indicates that decompression of the dilated pancreatic duct, although an effective means for relief of pain in chronic pancreatitis, does not prevent continuing destruction of pancreatic glandular tissue.

[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.

A learning progression based teaching module on the causes of seasons

NASA Astrophysics Data System (ADS)

Galano, S.

2016-03-01

In this paper, we report about designing and validating a teaching learning module based on a learning progression and focused on the causes of seasons. An initial learning progression about the Celestial Motion big idea -causes of seasons, lunar and solar eclipse and Moon phases- was developed and validated. Existing curricula, research studies on alternative conceptions about these phenomena, and students' answers to an open questionnaire were the starting point to develop initial learning progressions; then, a two-tier multiple-choice questionnaire was designed to validate and improve it. The questionnaire was submitted to about 300 secondary-school students whose answers were used to revise the hypothesized learning progressions. This improved version of the learning progression was used to design a module focused on the causes of seasons in which students were engaged in quantitative measurements with a photovoltaic panel to explain changes of the Sun rays' flow on the Earth's surface over the year. The efficacy of our module in improving students' understanding of the phenomenon of the seasons was tested using our questionnaire as pre- and post-test.

Adjuvant effect of Chakshushya Rasayana with beta-blocker eye drops in the management of progressive glaucomatous optic neuropathy: An open-label randomized controlled trial.

PubMed

Dhiman, K S; Adhoor, Veeranagouda S; Agarwal, Riju; Mehta, Amit J

2016-01-01

Primary open angle glaucoma is an insidious and chronic vision-threatening eye ailment due to neuro-retino-optic nerve degeneration, which may be due to the raised intraocular pressure (IOP) or due to independent factors. Management of glaucoma is mainly concentrated on lowering IOP that requires lifetime topical medication, different ocular medicaments for lowering of IOP, and surgical interventions, but it has its own limitations to control the progression of glaucomatous optic neuropathy (GON), and this is the reason behind the use of alternative neuroprotective adjuvants. To evaluate the neuroprotective effect of Ayurvedic line of management of progressive GON. Ingredients of trial drug Vara Fort powder ( Chakshushya Rasayana ) were procured from the Institute Pharmacy, except Swarnamakshika Bhasma , which was purchased from Dhootapapeshwar Pharmaceuticals. The patients fulfilling inclusion criteria, attending outpatient and inpatient departments, irrespective of their sex, race, religion, occupation, etc., were selected and divided into two groups with open-labeled randomization. In Group A, in addition to betaxolol (0.1%) or timolol (0.5%) (non-iobrim), Chakshushya Rasayana 6 g/day orally with Triphala Ghrita and honey along with Koshtha-Shuddhi (body-microchannel clearing treatment) protocol was tried. Nasya (oleation through nasal route) with Jeevantyadi Taila and Tarpana (eye satiation) with Go-Ghrita were also performed. In Group B (control), brimonidine (iobrim) 0.2% eye drop was used for 3 months. Significant improvement was observed in subjective parameters in Group A such as blurred vision, frequent change of presbyopic glasses, and delayed dark adaptation. Chakshushya Rasayana , if administered in a systematic approach along with a modern topical betaxolol or timolol eye drops, has a definite role in improving the lost retinal sensitivity as much as up to 12 dB in 3 months duration.

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

PubMed

Mehrabian, Zara; Guo, Yan; Weinreich, Daniel; Bernstein, Steven L

2017-01-01

Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies.

Review of GEM Radiation Belt Dropout and Buildup Challenges

NASA Astrophysics Data System (ADS)

Tu, Weichao; Li, Wen; Morley, Steve; Albert, Jay

2017-04-01

In Summer 2015 the US NSF GEM (Geospace Environment Modeling) focus group named "Quantitative Assessment of Radiation Belt Modeling" started the "RB dropout" and "RB buildup" challenges, focused on quantitative modeling of the radiation belt buildups and dropouts. This is a community effort which includes selecting challenge events, gathering model inputs that are required to model the radiation belt dynamics during these events (e.g., various magnetospheric waves, plasmapause and density models, electron phase space density data), simulating the challenge events using different types of radiation belt models, and validating the model results by comparison to in situ observations of radiation belt electrons (from Van Allen Probes, THEMIS, GOES, LANL/GEO, etc). The goal is to quantitatively assess the relative importance of various acceleration, transport, and loss processes in the observed radiation belt dropouts and buildups. Since 2015, the community has selected four "challenge" events under four different categories: "storm-time enhancements", "non-storm enhancements", "storm-time dropouts", and "non-storm dropouts". Model inputs and data for each selected event have been coordinated and shared within the community to establish a common basis for simulations and testing. Modelers within and outside US with different types of radiation belt models (diffusion-type, diffusion-convection-type, test particle codes, etc.) have participated in our challenge and shared their simulation results and comparison with spacecraft measurements. Significant progress has been made in quantitative modeling of the radiation belt buildups and dropouts as well as accessing the modeling with new measures of model performance. In this presentation, I will review the activities from our "RB dropout" and "RB buildup" challenges and the progresses achieved in understanding radiation belt physics and improving model validation and verification.

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

PubMed Central

Mehrabian, Zara; Guo, Yan; Weinreich, Daniel

2017-01-01

Purpose Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline’s post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)–neuroprotective ability. Methods We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Results Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. Conclusions The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies. PMID:29386871

Efficient selective screening for heart failure in elderly men and women from the community: A diagnostic individual participant data meta-analysis

PubMed Central

Kievit, Rogier F; Hoes, Arno W; Bots, Michiel L; van Riet, Evelien ES; van Mourik, Yvonne; Bertens, Loes CM; Boonman-de Winter, Leandra JM; den Ruijter, Hester M; Rutten, Frans H

2018-01-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64–0.76) to 0.82 (95% CI 0.78–0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70–0.81) to 0.89 (95% CI 0.86–0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure. PMID:29327942

Efficient selective screening for heart failure in elderly men and women from the community: A diagnostic individual participant data meta-analysis.

PubMed

Kievit, Rogier F; Gohar, Aisha; Hoes, Arno W; Bots, Michiel L; van Riet, Evelien Es; van Mourik, Yvonne; Bertens, Loes Cm; Boonman-de Winter, Leandra Jm; den Ruijter, Hester M; Rutten, Frans H

2018-03-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64-0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86-0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

Higher heritabilities for gait components than for overall gait scores may improve mobility in ducks.

PubMed

Duggan, Brendan M; Rae, Anne M; Clements, Dylan N; Hocking, Paul M

2017-05-02

Genetic progress in selection for greater body mass and meat yield in poultry has been associated with an increase in gait problems which are detrimental to productivity and welfare. The incidence of suboptimal gait in breeding flocks is controlled through the use of a visual gait score, which is a subjective assessment of walking ability of each bird. The subjective nature of the visual gait score has led to concerns over its effectiveness in reducing the incidence of suboptimal gait in poultry through breeding. The aims of this study were to assess the reliability of the current visual gait scoring system in ducks and to develop a more objective method to select for better gait. Experienced gait scorers assessed short video clips of walking ducks to estimate the reliability of the current visual gait scoring system. Kendall's coefficients of concordance between and within observers were estimated at 0.49 and 0.75, respectively. In order to develop a more objective scoring system, gait components were visually scored on more than 4000 pedigreed Pekin ducks and genetic parameters were estimated for these components. Gait components, which are a more objective measure, had heritabilities that were as good as, or better than, those of the overall visual gait score. Measurement of gait components is simpler and therefore more objective than the standard visual gait score. The recording of gait components can potentially be automated, which may increase accuracy further and may improve heritability estimates. Genetic correlations were generally low, which suggests that it is possible to use gait components to select for an overall improvement in both economic traits and gait as part of a balanced breeding programme.

Effectiveness of applying progressive muscle relaxation technique on quality of life of patients with multiple sclerosis.

PubMed

Ghafari, Somayeh; Ahmadi, Fazlolah; Nabavi, Masoud; Anoshirvan, Kazemnejad; Memarian, Robabe; Rafatbakhsh, Mohamad

2009-08-01

To identify the effects of applying Progressive Muscle Relaxation Technique on Quality of Life of patients with multiple Sclerosis. In view of the growing caring options in Multiple Sclerosis, improvement of quality of life has become increasingly relevant as a caring intervention. Complementary therapies are widely used by multiple sclerosis patients and Progressive Muscle Relaxation Technique is a form of complementary therapies. Quasi-experimental study. Multiple Sclerosis patients (n = 66) were selected with no probability sampling then assigned to experimental and control groups (33 patients in each group). Means of data collection included: Individual Information Questionnaire, SF-8 Health Survey, Self-reported checklist. PMRT performed for 63 sessions by experimental group during two months but no intervention was done for control group. Statistical analysis was done by SPSS software. Student t-test showed that there was no significant difference between two groups in mean scores of health-related quality of life before the study but this test showed a significant difference between two groups, one and two months after intervention (p < 0.05). anova test with repeated measurements showed that there is a significant difference in mean score of whole and dimensions of health-related quality of life between two groups in three times (p < 0.05). Although this study provides modest support for the effectiveness of Progressive Muscle Relaxation Technique on quality of life of multiple sclerosis patients, further research is required to determine better methods to promote quality of life of patients suffer multiple sclerosis and other chronic disease. Progressive Muscle Relaxation Technique is practically feasible and is associated with increase of life quality of multiple sclerosis patients; so that health professionals need to update their knowledge about complementary therapies.

Progression of fibrosis in usual interstitial pneumonia: serial evaluation of the native lung after single lung transplantation.

PubMed

Grgic, Aleksandar; Lausberg, Henning; Heinrich, Marc; Koenig, Jochem; Uder, Michael; Sybrecht, Gerhard W; Wilkens, Heinrike

2008-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. This retrospective observational study included 13 patients (24-64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0-5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0-5 for each lobe]. A comparison of serial changes (interval: 12-96 months posttransplant, 2-4 HRCT examinations/patient) was performed with the sign test. Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 +/- 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 +/- 0.26/year; p = 0.5). A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF. Copyright 2007 S. Karger AG, Basel.

Effect of fluoxetine on disease progression in a mouse model of ALS

PubMed Central

Koschnitzky, J. E.; Quinlan, K. A.; Lukas, T. J.; Kajtaz, E.; Kocevar, E. J.; Mayers, W. F.; Siddique, T.

2014-01-01

Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5–11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1G93A and control: nontransgenic and SOD1WT) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1G93A mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. PMID:24598527

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma.

PubMed

Maráz, Anikó; Cserháti, Adrienn; Uhercsák, Gabriella; Szilágyi, Éva; Varga, Zoltán; Révész, János; Kószó, Renáta; Varga, Linda; Kahán, Zsuzsanna

2018-03-15

In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%. Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.

Using and Reporting the Delphi Method for Selecting Healthcare Quality Indicators: A Systematic Review

PubMed Central

Boulkedid, Rym; Abdoul, Hendy; Loustau, Marine; Sibony, Olivier; Alberti, Corinne

2011-01-01

Objective Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. Methodology and Main Finding Three electronic data bases were searched over a 30 years period (1978–2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. Conclusion The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys. PMID:21694759

Using and reporting the Delphi method for selecting healthcare quality indicators: a systematic review.

PubMed

Boulkedid, Rym; Abdoul, Hendy; Loustau, Marine; Sibony, Olivier; Alberti, Corinne

2011-01-01

Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys.

Comparison of the progressive resolution optimizer and photon optimizer in VMAT optimization for stereotactic treatments.

PubMed

Liu, Han; Sintay, Benjamin; Pearman, Keith; Shang, Qingyang; Hayes, Lane; Maurer, Jacqueline; Vanderstraeten, Caroline; Wiant, David

2018-05-20

The photon optimization (PO) algorithm was recently released by Varian Medical Systems to improve volumetric modulated arc therapy (VMAT) optimization within Eclipse (Version 13.5). The purpose of this study is to compare the PO algorithm with its predecessor, progressive resolution optimizer (PRO) for lung SBRT and brain SRS treatments. A total of 30 patients were selected retrospectively. Previously, all the plans were generated with the PRO algorithm within Eclipse Version 13.6. In the new version of PO algorithm (Version 15), dynamic conformal arcs (DCA) were first conformed to the target, then VMAT inverse planning was performed to achieve the desired dose distributions. PTV coverages were forced to be identical for the same patient for a fair comparison. SBRT plan quality was assessed based on selected dose-volume parameters, including the conformity index, V 20 for lung, V 30 Gy for chest wall, and D 0.035 cc for other critical organs. SRS plan quality was evaluated based on the conformity index and normal tissue volumes encompassed by the 12 and 6 Gy isodose lines (V 12 and V 6 ). The modulation complexity score (MCS) was used to compare plan complexity of two algorithms. No statistically significant differences between the PRO and PO algorithms were found for any of the dosimetric parameters studied, which indicates both algorithms produce comparable plan quality. Significant improvements in the gamma passing rate (increased from 97.0% to 99.2% for SBRT and 96.1% to 98.4% for SRS), MCS (average increase of 0.15 for SBRT and 0.10 for SRS), and delivery efficiency (MU reduction of 29.8% for SBRT and 28.3% for SRS) were found for the PO algorithm. MCS showed a strong correlation with the gamma passing rate, and an inverse correlation with total MUs used. The PO algorithm offers comparable plan quality to the PRO, while minimizing MLC complexity, thereby improving the delivery efficiency and accuracy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Selecting and Buying Educational Software.

ERIC Educational Resources Information Center

Ahl, David H.

1983-01-01

Guidelines for selecting/buying educational software are discussed under the following headings: educational soundness; appropriateness; challenge and progress; motivation and reward; correctness; compatibility with systems; instructions and handlings. Includes several sources of software reviews. (JN)

Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?

PubMed Central

Singhal, Nitin; Vallam, Karthik; Engineer, Reena; Ostwal, Vikas; Arya, Supreeta

2016-01-01

Background Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Methods Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Results Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Conclusions Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease. PMID:27284467

Medical management of heavy menstrual bleeding

PubMed Central

Maybin, Jacqueline A; Critchley, Hilary OD

2016-01-01

Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations. PMID:26695687

Electronic toolkit for nursing education.

PubMed

Trangenstein, Patricia A

2008-12-01

In an ever-increasing hectic and mobile society, Web-based instructional tools can enhance and supplement student learning and improve communication and collaboration among participants, give rapid feedback on one's progress, and address diverse ways of learning. Web-based formats offer distinct advantages by allowing the learner to view course materials when they choose, from any Internet connection, and as often as they want. The challenge for nurse educators is to assimilate the knowledge and expertise to understand and appropriately use these tools. A variety of Web-based instructional tools are described in this article. As nurse educators increase their awareness of these potential adjuncts they can select appropriate applications that are supported by their institution to construct their own "toolkit."

Data Sharing: Convert Challenges into Opportunities.

PubMed

Figueiredo, Ana Sofia

2017-01-01

Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data.

Data Sharing: Convert Challenges into Opportunities

PubMed Central

Figueiredo, Ana Sofia

2017-01-01

Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data. PMID:29270401

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

PubMed Central

Park, Young Gun; Roh, Young-Jung

2016-01-01

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID:26881240

The growing and glowing toolbox of fluorescent and photoactive proteins

PubMed Central

Rodriguez, Erik A.; Campbell, Robert E.; Lin, John Y.; Lin, Michael Z.; Miyawaki, Atsushi; Palmer, Amy E.; Shu, Xiaokun; Zhang, Jin

2016-01-01

Over the past 20 years, protein engineering has been extensively used to improve and modify the fundamental properties of fluorescent proteins (FPs) with the goal of adapting them for a fantastic range of applications. FPs have been modified by a combination of rational design, structure-based mutagenesis, and countless cycles of directed evolution (gene diversification followed by selection of clones with desired properties) that have collectively pushed the properties to photophysical and biochemical extremes. In this review, we attempt to provide both a summary of the progress that has been made during the past two decades, and a broad overview of the current state of FP development and applications in mammalian systems. PMID:27814948

Advances in Mid-Infrared Spectroscopy for Chemical Analysis

NASA Astrophysics Data System (ADS)

Haas, Julian; Mizaikoff, Boris

2016-06-01

Infrared spectroscopy in the 3-20 μm spectral window has evolved from a routine laboratory technique into a state-of-the-art spectroscopy and sensing tool by benefitting from recent progress in increasingly sophisticated spectra acquisition techniques and advanced materials for generating, guiding, and detecting mid-infrared (MIR) radiation. Today, MIR spectroscopy provides molecular information with trace to ultratrace sensitivity, fast data acquisition rates, and high spectral resolution catering to demanding applications in bioanalytics, for example, and to improved routine analysis. In addition to advances in miniaturized device technology without sacrificing analytical performance, selected innovative applications for MIR spectroscopy ranging from process analysis to biotechnology and medical diagnostics are highlighted in this review.

Complete Metabolic Response of Advanced Melanoma to Vemurafenib Assessed with FDG-PET-CT at 85 Hours.

PubMed

Pascal, Pierre; Dercle, Laurent; Weyts, Kathleen; Meyer, Nicolas; Courbon, Fréderic

2018-05-01

Vemurafenib improves the management of advanced melanoma due to selective inhibition of the mutated BRAF V600E kinase. FDG-PET-CT is a tool for the evaluation of the biologic impact of inhibiting mutant BRAF. With vemurafenib at day 15, all the patients had at least partial metabolic response. Reductions in uptake correlate with longer progression free survival. In this case, incomplete information provided by the patient led to the performance of his third PET 85 hours after the introduction of vemurafenib. This early case of complete metabolic response suggests that FDG-PET-CT is a useful marker of early biologic response to vemurafenib.

Optimizing the selection of small-town wastewater treatment processes

NASA Astrophysics Data System (ADS)

Huang, Jianping; Zhang, Siqi

2018-04-01

Municipal wastewater treatment is energy-intensive. This high energy consumption causes high sewage treatment plant operating costs and increases the energy burden. To mitigate the adverse impacts of China’s development, sewage treatment plants should adopt effective energy-saving technologies. Artificial fortified natural water treatment and use of activated sludge and biofilm are all suitable technologies for small-town sewage treatment. This study features an analysis of the characteristics of small and medium-sized township sewage, an overview of current technologies, and a discussion of recent progress in sewage treatment. Based on this, an analysis of existing problems in municipal wastewater treatment is presented, and countermeasures to improve sewage treatment in small and medium-sized towns are proposed.

Evolution of endovascular stroke therapies and devices.

PubMed

Wallace, Adam N; Kansagra, Akash P; McEachern, James; Moran, Christopher J; Cross, Dewitte T; Derdeyn, Colin P

2016-01-01

Acute ischemic stroke is caused by occlusion of a cerebral artery, resulting in loss of brain tissue and neurologic deficits. However, a portion of the ischemic brain can be salvaged if blood flow is restored within an appropriate time frame. The past year has seen the publication of five positive randomized controlled trials demonstrating substantial benefit of mechanical thrombectomy in select patients with large vessel cerebrovascular occlusion. This progress is related to several factors, but most importantly, dramatic improvements in speed and rates of recanalization with the latest generation devices. In this article, we review the evolution of endovascular acute ischemic stroke therapies and key design features of the most widely used devices.

Novel targets and stimulation paradigms for deep brain stimulation.

PubMed

De Jesus, Sol; Almeida, Leonardo; Peng-Chen, Zhongxing; Okun, Michael S; Hess, Christopher W

2015-01-01

Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

Exercise Improves Cognition in Parkinson’s Disease: the PRET-PD Randomized Clinical Trial

PubMed Central

David, Fabian J.; Robichaud, Julie A.; Leurgans, Sue E.; Poon, Cynthia; Kohrt, Wendy M.; Goldman, Jennifer G.; Comella, Cynthia L.; Vaillancourt, David E.; Corcos, Daniel M.

2015-01-01

Background This paper reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes which were gathered as part of the Progressive Resistance Exercise Training in Parkinson’s disease randomized controlled trial. Methods This study was a prospective, parallel-group, single-center trial. Fifty-one non-demented patients with mild-to-moderate Parkinson’s disease were randomly assigned either to modified Fitness Counts or to Progressive Resistance Exercise, and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention. Results Eighteen patients in modified Fitness Counts and 20 patients in Progressive Resistance Exercise completed the trial. At 12 and at 24 months no differences between groups were observed. At 12 months, relative to baseline, modified Fitness Counts improved on the Digit Span (estimated change, 0.3; Inter-Quartile Range, 0, 0.7; p=0.04) and Stroop (0.3; 0, 0.6; p=0.04), and Progressive Resistance Exercise improved only on the Digit Span (0.7; 0.3, 1; p<0.01). At 24 months, relative to baseline, modified Fitness Counts improved on the Digit Span (0.7; 0.3, 1.7; p<0.01) and Stroop (0.3; 0.1, 0.5; p=0.03), while Progressive Resistance Exercise improved on the Digit Span (0.5; 0.2, 0.8; p<0.01), Stroop (0.2; −0.1, 0.6; p=0.048), and Brief Test of Attention (0.3; 0, 0.8; p=0.048). No neurologic or cognitive adverse events were seen. Conclusions This study provides Class IV level of evidence that 24 months of Progressive Resistance Exercise or modified Fitness Counts may improve attention and working memory in non-demented patients with mild-to-moderate Parkinson’s disease. PMID:26148003

Modelling gene expression profiles related to prostate tumor progression using binary states

PubMed Central

2013-01-01

Background Cancer is a complex disease commonly characterized by the disrupted activity of several cancer-related genes such as oncogenes and tumor-suppressor genes. Previous studies suggest that the process of tumor progression to malignancy is dynamic and can be traced by changes in gene expression. Despite the enormous efforts made for differential expression detection and biomarker discovery, few methods have been designed to model the gene expression level to tumor stage during malignancy progression. Such models could help us understand the dynamics and simplify or reveal the complexity of tumor progression. Methods We have modeled an on-off state of gene activation per sample then per stage to select gene expression profiles associated to tumor progression. The selection is guided by statistical significance of profiles based on random permutated datasets. Results We show that our method identifies expected profiles corresponding to oncogenes and tumor suppressor genes in a prostate tumor progression dataset. Comparisons with other methods support our findings and indicate that a considerable proportion of significant profiles is not found by other statistical tests commonly used to detect differential expression between tumor stages nor found by other tailored methods. Ontology and pathway analysis concurred with these findings. Conclusions Results suggest that our methodology may be a valuable tool to study tumor malignancy progression, which might reveal novel cancer therapies. PMID:23721350

The role of technical advances in the adoption and integration of patient-reported outcomes in clinical care.

PubMed

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

2015-02-01

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

The use of medication in selective mutism: a systematic review.

PubMed

Manassis, Katharina; Oerbeck, Beate; Overgaard, Kristin Romvig

2016-06-01

Despite limited evidence, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are used to reduce symptoms of selective mutism (SM) in children unresponsive to psychosocial interventions. We review existing evidence for the efficacy of these medications, limitations of the literature, and resulting treatment considerations. Bibliographic searches were conducted in Medline, Embase, PsycInfo, Web of Science and Cochrane up to June 2015. Two reviewers independently sought studies of children with SM as primary psychiatric diagnosis, which reported response to medication treatment. Abstracts were limited to those reporting original data. Two reviewers independently assessed the ten papers reporting on >2 subjects regarding study design, key results, and limitations. Heterogeneity of designs mandated a descriptive summary. Symptomatic improvement was found for 66/79 children treated with SSRIs and 4/4 children treated with phenelzine. Only 3/10 studies had unmedicated comparison groups and only two were double-blinded. This review may be affected by publication bias, missed studies, and variability of outcome measures in included studies. Although there is some evidence for symptomatic improvement in SM with medication, especially SSRIs, it is limited by small numbers, lack of comparative trials, lack of consistent measures, and lack of consistent reporting on tolerability. The clinician must weigh this paucity of evidence against the highly debilitating nature of SM, and its adverse effects on the development of those children whose progress with psychosocial interventions is limited or very slow. Studies of optimal dosage and timing of medications in relation to psychosocial treatments are also needed.

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

PubMed Central

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

2016-01-01

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

Primary Care Clinic Re-Design for Prescription Opioid Management.

PubMed

Parchman, Michael L; Von Korff, Michael; Baldwin, Laura-Mae; Stephens, Mark; Ike, Brooke; Cromp, DeAnn; Hsu, Clarissa; Wagner, Ed H

The challenge of responding to prescription opioid overuse within the United States has fallen disproportionately on the primary care clinic setting. Here we describe a framework comprised of 6 Building Blocks to guide efforts within this setting to address the use of opioids for chronic pain. Investigators conducted site visits to thirty primary care clinics across the United States selected for their use of team-based workforce innovations. Site visits included interviews with leadership, clinic tours, observations of clinic processes and team meetings, and interviews with staff and clinicians. Data were reviewed to identify common attributes of clinic system changes around chronic opioid therapy (COT) management. These concepts were reviewed to develop narrative descriptions of key components of changes made to improve COT use. Twenty of the thirty sites had addressed improvements in COT prescribing. Across these sites a common set of 6 Building Blocks were identified: 1) providing leadership support; 2) revising and aligning clinic policies, patient agreements (contracts) and workflows; 3) implementing a registry tracking system; 4) conducting planned, patient-centered visits; 5) identifying resources for complex patients; and 6) measuring progress toward achieving clinic objectives. Common components of clinic policies, patient agreements and data tracked in registries to assess progress are described. In response to prescription opioid overuse and the resulting epidemic of overdose and addiction, primary care clinics are making improvements driven by a common set of best practices that address complex challenges of managing COT patients in primary care settings. © Copyright 2017 by the American Board of Family Medicine.

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases.

PubMed

Snowden, John A; Badoglio, Manuela; Labopin, Myriam; Giebel, Sebastian; McGrath, Eoin; Marjanovic, Zora; Burman, Joachim; Moore, John; Rovira, Montserrat; Wulffraat, Nico M; Kazmi, Majid; Greco, Raffaella; Snarski, Emilian; Kozak, Tomas; Kirgizov, Kirill; Alexander, Tobias; Bader, Peter; Saccardi, Riccardo; Farge, Dominique

2017-12-26

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index ( P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10 -5 ), relapse/progression ( P < 10 -5 ), and nonrelapse mortality ( P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status ( P = .02). Despite improved survival over time ( P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.

Clinical Decision Support: a 25 Year Retrospective and a 25 Year Vision

PubMed Central

Sittig, D. F.; Wright, A.

2016-01-01

Summary Objective The objective of this review is to summarize the state of the art of clinical decision support (CDS) circa 1990, review progress in the 25 year interval from that time, and provide a vision of what CDS might look like 25 years hence, or circa 2040. Method Informal review of the medical literature with iterative review and discussion among the authors to arrive at six axes (data, knowledge, inference, architecture and technology, implementation and integration, and users) to frame the review and discussion of selected barriers and facilitators to the effective use of CDS. Result In each of the six axes, significant progress has been made. Key advances in structuring and encoding standardized data with an increased availability of data, development of knowledge bases for CDS, and improvement of capabilities to share knowledge artifacts, explosion of methods analyzing and inferring from clinical data, evolution of information technologies and architectures to facilitate the broad application of CDS, improvement of methods to implement CDS and integrate CDS into the clinical workflow, and increasing sophistication of the end-user, all have played a role in improving the effective use of CDS in healthcare delivery. Conclusion CDS has evolved dramatically over the past 25 years and will likely evolve just as dramatically or more so over the next 25 years. Increasingly, the clinical encounter between a clinician and a patient will be supported by a wide variety of cognitive aides to support diagnosis, treatment, care-coordination, surveillance and prevention, and health maintenance or wellness. PMID:27488402

Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

PubMed

Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

2016-09-01

Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Time to competency, reliability of flexible transnasal laryngoscopy by training level: a pilot study.

PubMed

Brook, Christopher D; Platt, Michael P; Russell, Kimberly; Grillone, Gregory A; Aliphas, Avner; Noordzij, J Pieter

2015-05-01

To determine the progression of flexible transnasal laryngoscopy reliability and competency in otolaryngology residency training. Prospective case control study. Academic otolaryngology department. Medical students, otolaryngology residents, and otolaryngology attending physicians. Fourteen otolaryngology residents from PGY-1 to PGY-5 and 3 attending otolaryngologists viewed 25 selected and digitally recorded flexible transnasal laryngoscopies. The evaluators were asked to rate 13 items relating to abnormalities in the oropharynx, hypopharynx, larynx, and subglottis. The level of concern and level of comfort with the diagnosis were assessed. Intraclass correlations were calculated for each topic and by level of training to determine reliability within each class and compare competency versus attending interpretations. Intraclass correlation of residents compared to attending physicians demonstrated significant improvements by year for left and right vocal fold immobility, subglottic stenosis, laryngeal mass, left and right vocal cord abnormalities, and level of concern. Additionally, pooled vocal cord mobility and pooled results in categories with good attending reliability demonstrated stepwise improvement as well. For these categories, resident reliability was found to be statistically similar to attending physicians in all categories by PGY-3. There were no trends for base of tongue abnormalities, pharyngeal abnormalities, and pharyngeal and hypopharyngeal masses. Resident competency for flexible transnasal laryngoscopy progresses during residency to reliability with attending otolaryngologists by the PGY-3 year over key facets of the examination. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

Monitoring Results in Routine Immunization: Development of Routine Immunization Dashboard in Selected African Countries in the Context of the Polio Eradication Endgame Strategic Plan.

PubMed

Poy, Alain; van den Ent, Maya M V X; Sosler, Stephen; Hinman, Alan R; Brown, Sidney; Sodha, Samir; Ehlman, Daniel C; Wallace, Aaron S; Mihigo, Richard

2017-07-01

To monitor immunization-system strengthening in the Polio Eradication Endgame Strategic Plan 2013-2018 (PEESP), the Global Polio Eradication Initiative identified 1 indicator: 10% annual improvement in third dose of diphtheria- tetanus-pertussis-containing vaccine (DTP3) coverage in polio high-risk districts of 10 polio focus countries. A multiagency team, including staff from the African Region, developed a comprehensive list of outcome and process indicators measuring various aspects of the performance of an immunization system. The development and implementation of the dashboard to assess immunization system performance allowed national program managers to monitor the key immunization indicators and stratify by high-risk and non-high-risk districts. Although only a single outcome indicator goal (at least 10% annual increase in DTP3 coverage achieved in 80% of high-risk districts) initially existed in the endgame strategy, we successfully added additional outcome indicators (eg, decreasing the number of DTP3-unvaccinated children) as well as program process indicators focusing on cold chain, stock availability, and vaccination sessions to better describe progress on the pathway to raising immunization coverage. When measuring progress toward improving immunization systems, it is helpful to use a comprehensive approach that allows for measuring multiple dimensions of the system. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Pathological Bases for a Robust Application of Cancer Molecular Classification

PubMed Central

Diaz-Cano, Salvador J.

2015-01-01

Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification) and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes), and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors. PMID:25898411

Liver transplantation: Current status and challenges

PubMed Central

Jadlowiec, Caroline C; Taner, Timucin

2016-01-01

Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155

Diversity pattern in Sesamum mutants selected for a semi-arid cropping system.

PubMed

Murty, B R; Oropeza, F

1989-02-01

Due to the complex requirements of moisture stress, substantial genetic diversity with a wide array of character combinations and effective simultaneous selection for several variables is necessary for improving the productivity and adaptation of a component crop in order for it to fit into a cropping system under semi-arid tropical conditions. Sesamum indicum L. is grown in Venezuela after rice/sorghum/or maize under such conditions. A mutation breeding program was undertaken using six locally adapted varieties to develop genotypes suitable for the above system. The diversity pattern for nine variables was assessed by multivariate analysis in 301 M4 progenies. Analysis of the characteristic roots and principal components in three methods of selection, i.e., M2 bulks (A), individual plant selection throughout (B), and selection in M3 for single variable (C), revealed differences in the pattern of variation between varieties, selection methods, and varieties x methods interactions. Method B was superior to the others and gave 17 of the 21 best M5 progenies. 'Piritu' and 'CF' varieties yielded the most productive progenies in M5 and M6. Diversity was large and selection was effective for such developmental traits as earliness and synchrony, combined with multiple disease resistance, which could be related to their importance by multivariate analyses. Considerable differences in the variety of character combinations among the high yielding. M5 progenies of 'CF' and 'Piritu' suggested possible further yield improvement. The superior response of 'Piritu' and 'CF' over other varieties in yield and adaptation was due to major changes in plant type and character associations. Multilocation testing of M5 generations revealed that the mutant progenies had a 40%-100% yield superiority over the parents; this was combined with earliness, synchrony, and multiple disease resistance, and was confirmed in the M6 generation grown on a commercial scale. This study showed that multivariate analysis is an effective tool for assessing diversity patterns, choice of appropriate variety, and selection methodology in order to make rapid progress in meeting the complex requirements of semi-arid cropping systems.

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

PubMed

Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

2018-03-06

In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Expanding Omics Resources for Improvement of Soybean Seed Composition Traits

PubMed Central

Chaudhary, Juhi; Patil, Gunvant B.; Sonah, Humira; Deshmukh, Rupesh K.; Vuong, Tri D.; Valliyodan, Babu; Nguyen, Henry T.

2015-01-01

Food resources of the modern world are strained due to the increasing population. There is an urgent need for innovative methods and approaches to augment food production. Legume seeds are major resources of human food and animal feed with their unique nutrient compositions including oil, protein, carbohydrates, and other beneficial nutrients. Recent advances in next-generation sequencing (NGS) together with “omics” technologies have considerably strengthened soybean research. The availability of well annotated soybean genome sequence along with hundreds of identified quantitative trait loci (QTL) associated with different seed traits can be used for gene discovery and molecular marker development for breeding applications. Despite the remarkable progress in these technologies, the analysis and mining of existing seed genomics data are still challenging due to the complexity of genetic inheritance, metabolic partitioning, and developmental regulations. Integration of “omics tools” is an effective strategy to discover key regulators of various seed traits. In this review, recent advances in “omics” approaches and their use in soybean seed trait investigations are presented along with the available databases and technological platforms and their applicability in the improvement of soybean. This article also highlights the use of modern breeding approaches, such as genome-wide association studies (GWAS), genomic selection (GS), and marker-assisted recurrent selection (MARS) for developing superior cultivars. A catalog of available important resources for major seed composition traits, such as seed oil, protein, carbohydrates, and yield traits are provided to improve the knowledge base and future utilization of this information in the soybean crop improvement programs. PMID:26635846

High doses of biotin in chronic progressive multiple sclerosis: a pilot study.

PubMed

Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman

2015-03-01

No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Surgical improvement of speech disorder caused by amyotrophic lateral sclerosis.

PubMed

Saigusa, Hideto; Yamaguchi, Satoshi; Nakamura, Tsuyoshi; Komachi, Taro; Kadosono, Osamu; Ito, Hiroyuki; Saigusa, Makoto; Niimi, Seiji

2012-12-01

Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurological disease. ALS disturbs the quality of life by affecting speech, swallowing and free mobility of the arms without affecting intellectual function. It is therefore of significance to improve intelligibility and quality of speech sounds, especially for ALS patients with slowly progressive courses. Currently, however, there is no effective or established approach to improve speech disorder caused by ALS. We investigated a surgical procedure to improve speech disorder for some patients with neuromuscular diseases with velopharyngeal closure incompetence. In this study, we performed the surgical procedure for two patients suffering from severe speech disorder caused by slowly progressing ALS. The patients suffered from speech disorder with hypernasality and imprecise and weak articulation during a 6-year course (patient 1) and a 3-year course (patient 2) of slowly progressing ALS. We narrowed bilateral lateral palatopharyngeal wall at velopharyngeal port, and performed this surgery under general anesthesia without muscle relaxant for the two patients. Postoperatively, intelligibility and quality of their speech sounds were greatly improved within one month without any speech therapy. The patients were also able to generate longer speech phrases after the surgery. Importantly, there was no serious complication during or after the surgery. In summary, we performed bilateral narrowing of lateral palatopharyngeal wall as a speech surgery for two patients suffering from severe speech disorder associated with ALS. With this technique, improved intelligibility and quality of speech can be maintained for longer duration for the patients with slowly progressing ALS.

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

PubMed Central

Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-01-01

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis. PMID:27793017

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.

PubMed

Huang, Lihong; Wei, Yongyue; Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-04-25

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.

How to Measure and Interpret Quality Improvement Data.

PubMed

McQuillan, Rory Francis; Silver, Samuel Adam; Harel, Ziv; Weizman, Adam; Thomas, Alison; Bell, Chaim; Chertow, Glenn M; Chan, Christopher T; Nesrallah, Gihad

2016-05-06

This article will demonstrate how to conduct a quality improvement project using the change idea generated in "How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem" by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan-Do-Study-Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting. Copyright © 2016 by the American Society of Nephrology.

Progress in Modeling Nonlinear Dendritic Evolution in Two and Three Dimensions, and Its Mathematical Justification

NASA Technical Reports Server (NTRS)

Tanveer, S.; Foster, M. R.

2002-01-01

We report progress in three areas of investigation related to dendritic crystal growth. Those items include: 1. Selection of tip features dendritic crystal growth; 2) Investigation of nonlinear evolution for two-sided model; and 3) Rigorous mathematical justification.

Optimizing therapy for iron overload in the myelodysplastic syndromes: recent developments.

PubMed

Leitch, Heather A

2011-01-22

The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of progression to acute myeloid leukaemia (AML). Most MDS patients eventually require transfusion of red blood cells for anaemia, placing them at risk of transfusional iron overload. In β-thalassaemia major, transfusional iron overload leads to organ dysfunction and death; however, with iron chelation therapy, organ function is improved, and survival improved to near normal and correlated with the degree of compliance with chelation. In lower-risk MDS, several nonrandomized studies suggest an adverse effect of iron overload on survival and that lowering iron with chelation may minimize this impact. Emerging data indicate that chelation may improve organ function, particularly hepatic function, and a minority of patients may have improvement in cell counts and decreased transfusion requirements. While guidelines for MDS generally recommend chelation in selected lower-risk patients, data from nonrandomized trials suggest iron overload may impact adversely on the outcome of higher-risk MDS and stem cell transplantation (SCT). This effect may be due to increased transplant-related mortality, infection and AML progression, and preliminary data suggest that lowering iron may be beneficial in this patient group. Other areas of active and future investigation include optimizing the monitoring of iron overload using imaging such as T2* MRI and measures of labile iron and oxidative stress; correlating new methods of measuring iron to clinical outcomes; clarifying the contribution of different cellular and extracellular iron pools to iron toxicity; optimizing chelation by using agents that access the appropriate iron pools to minimize the relevant clinical consequences in individual patients; and incorporating measures of quality of life and co-morbidities into clinical trials of chelation in MDS. It should be noted that chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this review, data on the impact of iron overload in MDS and SCT are discussed; for example, several noncontrolled studies show inferior survival in patients with iron overload in these clinical settings, including an increase in transplant-related mortality and infection risk. Possible mechanisms of iron toxicity include oxidative stress, which can damage cellular components, and the documented impact of lowering iron on organ function with measures such as iron chelation therapy includes an improvement in elevated liver transaminases. Lowering iron also appears to improve survival in both lower-risk MDS and SCT in nonrandomized studies. Selected aspects of iron metabolism, transport, storage and distribution that may be amenable to future intervention and improved removal of iron from important cellular sites are discussed, as are attempts to quantify quality of life and the importance of co-morbidities in measures to treat MDS, including chelation therapy.

Better Measurement for Performance Improvement in Low- and Middle-Income Countries: The Primary Health Care Performance Initiative (PHCPI) Experience of Conceptual Framework Development and Indicator Selection.

PubMed

Veillard, Jeremy; Cowling, Krycia; Bitton, Asaf; Ratcliffe, Hannah; Kimball, Meredith; Barkley, Shannon; Mercereau, Laure; Wong, Ethan; Taylor, Chelsea; Hirschhorn, Lisa R; Wang, Hong

2017-12-01

Policy Points: Strengthening accountability through better measurement and reporting is vital to ensure progress in improving quality primary health care (PHC) systems and achieving universal health coverage (UHC). The Primary Health Care Performance Initiative (PHCPI) provides national decision makers and global stakeholders with opportunities to benchmark and accelerate performance improvement through better performance measurement. Results from the initial PHC performance assessments in low- and middle-income countries (LMICs) are helping guide PHC reforms and investments and improve the PHCPI's instruments and indicators. Findings from future assessment activities will further amplify cross-country comparisons and peer learning to improve PHC. New indicators and sources of data are needed to better understand PHC system performance in LMICs. The Primary Health Care Performance Initiative (PHCPI), a collaboration between the Bill and Melinda Gates Foundation, The World Bank, and the World Health Organization, in partnership with Ariadne Labs and Results for Development, was launched in 2015 with the aim of catalyzing improvements in primary health care (PHC) systems in 135 low- and middle-income countries (LMICs), in order to accelerate progress toward universal health coverage. Through more comprehensive and actionable measurement of quality PHC, the PHCPI stimulates peer learning among LMICs and informs decision makers to guide PHC investments and reforms. Instruments for performance assessment and improvement are in development; to date, a conceptual framework and 2 sets of performance indicators have been released. The PHCPI team developed the conceptual framework through literature reviews and consultations with an advisory committee of international experts. We generated 2 sets of performance indicators selected from a literature review of relevant indicators, cross-referenced against indicators available from international sources, and evaluated through 2 separate modified Delphi processes, consisting of online surveys and in-person facilitated discussions with experts. The PHCPI conceptual framework builds on the current understanding of PHC system performance through an expanded emphasis on the role of service delivery. The first set of performance indicators, 36 Vital Signs, facilitates comparisons across countries and over time. The second set, 56 Diagnostic Indicators, elucidates underlying drivers of performance. Key challenges include a lack of available data for several indicators and a lack of validated indicators for important dimensions of quality PHC. The availability of data is critical to assessing PHC performance, particularly patient experience and quality of care. The PHCPI will continue to develop and test additional performance assessment instruments, including composite indices and national performance dashboards. Through country engagement, the PHCPI will further refine its instruments and engage with governments to better design and finance primary health care reforms. © 2017 Milbank Memorial Fund.

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

Venteris, Erik R.; McBride, Robert; Coleman, Andre M.

Locating sites for new algae cultivation facilities is a complex task. The climate must support high growth rates, and cultivation ponds require appropriate land and water resources as well as key utility and transportation infrastructure. We employ our spatiotemporal Biomass Assessment Tool (BAT) to select promising locations based on the open-pond cultivation of Arthrospira sp. and a strain of the order Desmidiales. 64,000 potential sites across the southern United States were evaluated. We progressively apply a range of screening criteria and track their impact on the number of selected sites, geographic location, and biomass productivity. Both strains demonstrate maximum productivitymore » along the Gulf of Mexico coast, with the highest values on the Florida peninsula. In contrast, sites meeting all selection criteria for Arthrospira were located along the southern coast of Texas and for Desmidiales were located in Louisiana and southern Arkansas. Site selection was driven mainly by the lack of oil pipeline access in Florida and elevated groundwater salinity in southern Texas. The requirement for low salinity freshwater (<400 mg L-1) constrained Desmidiales locations; siting flexibility is greater for salt-tolerant species such as Arthrospira. Combined siting factors can result in significant departures from regions of maximum productivity but are within the expected range of site-specific process improvements.« less

Are We Nearly There Yet? Progress, Issues, and Possible Next Steps for a Self-Improving School System. Inaugural Professorial Lecture

ERIC Educational Resources Information Center

Greany, Toby

2014-01-01

The DfE's 2010 white paper "The Importance of Teaching" set out the Coalition's aim to "create a school system which is self-improving". In this inaugural lecture, Toby Greany assesses progress to date and the Coalition Government's approach to developing a self-improving system. He argues that the Coalition is following at…

A Continuous Quality Improvement Approach to Discipline.

ERIC Educational Resources Information Center

Norian, Nicole A.; Michaud, Paul J.

This monograph offers information on basic procedures concerning disciplinary action in a continuous quality improvement setting at an institution of higher education. In particular it describes progressive discipline, the application of positive discipline in a series of steps that gradually increase in severity as an employee progresses through…

Psychological interventions in the management of common skin conditions

PubMed Central

Shenefelt, Philip D

2010-01-01

The nervous system and the skin develop next to each other in the embryo and remain intimately interconnected and interactive throughout life. The nervous system can influence skin conditions through psychoneuroimmunoendocrine mechanisms and through behaviors. Understanding the pathophysiology aids in selection of treatment plans for correcting the negative effects of the psyche on specific skin conditions. Medication options include standard psychotropic medications and alternative herbs and supplements. Other options include biofeedback, cognitive-behavioral methods, hypnosis, meditation, progressive relaxation, the placebo effect, and suggestion. When simple measures fail, combining medications with other therapeutic options may produce better results. Skin conditions that have strong psychophysiologic aspects may respond well to techniques such as biofeedback, cognitive-behavioral methods, hypnosis, meditation, or progressive relaxation that help to counteract stress. Treatment of primary psychiatric disorders that negatively influence skin conditions often results in improvement of those skin conditions. Abnormal conditions of the skin, hair, and nails can also influence the psyche negatively. Treatment of secondary psychiatric disorders such as anxiety or depression that are triggered or exacerbated by the appearance of these skin conditions or the associated discomfort may also be required. PMID:22110329

MicroRNAs in right ventricular remodelling.

PubMed

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Therapeutic cancer vaccines: are we there yet?

PubMed Central

Klebanoff, Christopher A.; Acquavella, Nicholas; Yu, Zhiya; Restifo, Nicholas P.

2011-01-01

Summary Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways. PMID:21198663

Scientific progress despite irreproducibility: A seeming paradox

PubMed Central

Shiffrin, Richard M.; Stigler, Stephen M.

2018-01-01

It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly, the practice of science needs to be improved, and scientists are now pursuing this goal. However, in this perspective, we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox. We then review a wide range of challenges that appear to make scientific success difficult. Next, we describe the factors that make science work—in the past, present, and presumably also in the future. We then suggest that remedies for the present practice of science need to be applied selectively so as not to slow progress and illustrate with a few examples. We conclude with arguments that communication of science needs to emphasize not just problems but the enormous successes and benefits that science has brought and is now bringing to all elements of modern society. PMID:29531095

Molecular targeted therapy for advanced gastric cancer.

PubMed

Kim, Jong Gwang

2013-03-01

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

Core principles of assessment in competency-based medical education.

PubMed

Lockyer, Jocelyn; Carraccio, Carol; Chan, Ming-Ka; Hart, Danielle; Smee, Sydney; Touchie, Claire; Holmboe, Eric S; Frank, Jason R

2017-06-01

The meaningful assessment of competence is critical for the implementation of effective competency-based medical education (CBME). Timely ongoing assessments are needed along with comprehensive periodic reviews to ensure that trainees continue to progress. New approaches are needed to optimize the use of multiple assessors and assessments; to synthesize the data collected from multiple assessors and multiple types of assessments; to develop faculty competence in assessment; and to ensure that relationships between the givers and receivers of feedback are appropriate. This paper describes the core principles of assessment for learning and assessment of learning. It addresses several ways to ensure the effectiveness of assessment programs, including using the right combination of assessment methods and conducting careful assessor selection and training. It provides a reconceptualization of the role of psychometrics and articulates the importance of a group process in determining trainees' progress. In addition, it notes that, to reach its potential as a driver in trainee development, quality care, and patient safety, CBME requires effective information management and documentation as well as ongoing consideration of ways to improve the assessment system.

Microbial production of nattokinase: current progress, challenge and prospect.

PubMed

Cai, Dongbo; Zhu, Chengjun; Chen, Shouwen

2017-05-01

Nattokinase (EC 3.4.21.62) is a profibrinolytic serine protease with a potent fibrin-degrading activity, and it has been produced by many host strains. Compared to other fibrinolytic enzymes (urokinase, t-PA and streprokinase), nattokinase shows the advantages of having no side effects, low cost and long life-time, and it has the potential to be used as a drug for treating cardiovascular disease and served as a functional food additive. In this review, we focused on screening of producing strains, genetic engineering, fermentation process optimization for microbial nattokinase production, and the extraction and purification of nattokinase were also discussed in this particular chapter. The selection of optimal nattokinase producing strain was the crucial starting element for improvement of nattokinase production. Genetic engineering, protein engineering, fermentation optimization and process control have been proved to be the effective strategies for enhancement of nattokinase production. Also, extraction and purification of nattokinase are critical for the quality evaluation of nattokinase. Finally, the prospect of microbial nattokinase production was also discussed regarding the recent progress, challenge, and trends in this field.

Elevated PGC-1α activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS.

PubMed

Da Cruz, Sandrine; Parone, Philippe A; Lopes, Vanda S; Lillo, Concepción; McAlonis-Downes, Melissa; Lee, Sandra K; Vetto, Anne P; Petrosyan, Susanna; Marsala, Martin; Murphy, Anne N; Williams, David S; Spiegelman, Bruce M; Cleveland, Don W

2012-05-02

The transcriptional coactivator PGC-1α induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1α levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1α-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1α activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS. Copyright © 2012 Elsevier Inc. All rights reserved.

Maximizing the Therapeutic Potential of Hsp90 Inhibitors

PubMed Central

Butler, Lisa M.; Ferraldeschi, Roberta; Armstrong, Heather K.; Centenera, Margaret M.; Workman, Paul

2015-01-01

Hsp90 is required for maintaining the stability and activity of a diverse group of client proteins, including protein kinases, transcription factors and steroid hormone receptors involved in cell signaling, proliferation, survival, oncogenesis and cancer progression. Inhibition of Hsp90 alters the Hsp90-client protein complex, leading to reduced activity, misfolding, ubiquitination and, ultimately, proteasomal degradation of client proteins. Hsp90 inhibitors have demonstrated significant antitumor activity in a wide variety of preclinical models with evidence of selectivity for cancer versus normal cells. In the clinic however, the efficacy of this class of therapeutic agents has been relatively limited to date, with promising responses mainly observed in breast and lung cancer, but no major activity seen in other tumor types. In addition, adverse events and some significant toxicities have been documented. Key to improving these clinical outcomes is a better understanding of the cellular consequences of inhibiting Hsp90 that may underlie treatment response or resistance. This review considers the recent progress that has been made in the study of Hsp90 and its inhibitors, and highlights new opportunities to maximize their therapeutic potential. PMID:26219697

Resonance ionization laser ion sources for on-line isotope separators (invited).

PubMed

Marsh, B A

2014-02-01

A Resonance Ionization Laser Ion Source (RILIS) is today considered an essential component of the majority of Isotope Separator On Line (ISOL) facilities; there are seven laser ion sources currently operational at ISOL facilities worldwide and several more are under development. The ionization mechanism is a highly element selective multi-step resonance photo-absorption process that requires a specifically tailored laser configuration for each chemical element. For some isotopes, isomer selective ionization may even be achieved by exploiting the differences in hyperfine structures of an atomic transition for different nuclear spin states. For many radioactive ion beam experiments, laser resonance ionization is the only means of achieving an acceptable level of beam purity without compromising isotope yield. Furthermore, by performing element selection at the location of the ion source, the propagation of unwanted radioactivity downstream of the target assembly is reduced. Whilst advances in laser technology have improved the performance and reliability of laser ion sources and broadened the range of suitable commercially available laser systems, many recent developments have focused rather on the laser/atom interaction region in the quest for increased selectivity and/or improved spectral resolution. Much of the progress in this area has been achieved by decoupling the laser ionization from competing ionization processes through the use of a laser/atom interaction region that is physically separated from the target chamber. A new application of gas catcher laser ion source technology promises to expand the capabilities of projectile fragmentation facilities through the conversion of otherwise discarded reaction fragments into high-purity low-energy ion beams. A summary of recent RILIS developments and the current status of laser ion sources worldwide is presented.

Recent developments in nanostructured inorganic materials for sorption of cesium and strontium: Synthesis and shaping, sorption capacity, mechanisms, and selectivity-A review.

PubMed

Alby, Delhia; Charnay, Clarence; Heran, Marc; Prelot, Bénédicte; Zajac, Jerzy

2018-02-15

Liquid wastes containing non-ferrous heavy metal ions and some radionuclides, 137 Cs and 90 Sr in particular, represent one of the most dangerous sources of environmental contamination. The remediation of wastewater containing such pollutants continue to be among the biggest challenges of Sustainable Development and Environmental Safety. Sorption-based technologies have proven their efficiency also in reducing the radionuclide content in aqueous streams to low-level residual activity, with the concomitant decrease in the amount of ultimate solid waste generated. Although sorption of cesium and strontium by resins, clays, and zeolites has been investigated intensively and even used in real applications, there is still considerable scope for improvement in terms of retention capacity and selectivity. Recent progress in design and preparation of nanostructured inorganic materials has attracted growing interest based on the potential for improving the retention performance when coupling such functionalities as ion exchange capacity, structural flexibility that may result in steric retention effects, as well as the propensity to interact specifically with the target metal cations. Titanate, vanadate, and tungsten based materials, manganese oxides, hexacyanoferrates, metal sulfides, ammonium molybdophosphates, or hydroxyapatite, characterized by various structures and morphologies, are reviewed with the emphasis being put on synthesis and shaping of such materials, their structure in relationship with the capacity and selectivity of trapping cesium and strontium from either single or multi-component aqueous solutions, as well as the possible retention mechanism. The potential candidates for remediation uses are selected with regard to their sorption capacity and distribution coefficient towards target cations, and also the pH window for an optimum cation capture. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of lodgepole pine cover types by Yellowstone grizzly bears

USGS Publications Warehouse

Mattson, D.J.

1997-01-01

Lodgepole pine (Pinus contorta) forests are a large and dynamic part of grizzly bear (Ursus arctos) habitat in the Yellowstone ecosystem. Research in other areas suggests that grizzly bears select for young open forest stands, especially for grazing and feeding on berries. Management guidelines accordingly recommend timber harvest as a technique for improving habitat in areas potentially dominated by lodgepole pine. In this paper I examine grizzly bear use of lodgepole pine forests in the Yellowstone area, and test several hypotheses with relevance to a new generation of management guidelines. Differences in grizzly bear selection of lodgepole pine cover types (defined on the basis of stand age and structure) were not pronounced. Selection furthermore varied among years, areas, and individuals. Positive selection for any lodgepole pine type was uncommon. Estimates of selection took 5-11 years or 4-12 adult females to stabilize, depending upon the cover type. The variances of selection estimates tended to stabilize after 3-5 sample years, and were more-or-less stable to slightly increasing with progressively increased sample area. There was no conclusive evidence that Yellowstone's grizzlies favored young (<40 yr) stands in general or for their infrequent use of berries. On the other hand, these results corroborated previous observations that grizzlies favored open and/or young stands on wet and fertile sites for grazing. These results also supported the proposition that temporally and spatially robust inferences require extensive, long-duration studies, especially for wide-ranging vertebrates like grizzly bears.

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

PubMed Central

Pardiñas, Antonio F.; Holmans, Peter; Pocklington, Andrew J.; Escott-Price, Valentina; Ripke, Stephan; Carrera, Noa; Legge, Sophie E.; Bishop, Sophie; Cameron, Darren; Hamshere, Marian L.; Han, Jun; Hubbard, Leon; Lynham, Amy; Mantripragada, Kiran; Rees, Elliott; MacCabe, James H.; McCarroll, Steven A.; Baune, Bernhard T.; Breen, Gerome; Byrne, Enda M.; Dannlowski, Udo; Eley, Thalia C.; Hayward, Caroline; Martin, Nicholas G.; McIntosh, Andrew M.; Plomin, Robert; Porteous, David J.; Wray, Naomi R.; Caballero, Armando; Geschwind, Daniel H.; Huckins, Laura M.; Ruderfer, Douglas M.; Santiago, Enrique; Sklar, Pamela; Stahl, Eli A.; Won, Hyejung; Agerbo, Esben; Als, Thomas D.; Andreassen, Ole A.; Bækvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Børglum, Anders D.; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giørtz; Golimbet, Vera; Grove, Jakob; Hougaard, David M.; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Søholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; Collier, David A.; Rujescu, Dan; Kirov, George; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.

2018-01-01

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population. PMID:29483656

Exercise and Parkinson's: benefits for cognition and quality of life.

PubMed

Cruise, K E; Bucks, R S; Loftus, A M; Newton, R U; Pegoraro, R; Thomas, M G

2011-01-01

The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson's disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease-specific QoL for people with PD. Twenty-eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease-specific QoL. These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD. Copyright © 2010 The Authors. Journal compilation © 2010 Blackwell Munksgaard.

Individual Progress Toward Self-Selected Goals Among Older Adults Enrolled in a Physical Activity Counseling Intervention

PubMed Central

Hall, Katherine S.; Crowley, Gail M.; Bosworth, Hayden B.; Howard, Teresa A.; Morey, Miriam C.

2011-01-01

The purpose of this study was to examine what happens to goals over the course of a physical activity counseling trial in older veterans. At baseline, participants (N = 313) identified 1 health-related goal and 1 walking goal for their participation in the study and rated where they perceived themselves to be relative to that goal at the current time. They rated their current status on these same goals again at 6 and 12 mo. Growth-curve analyses were used to examine longitudinal change in perceived goal status. Although both the intervention and control groups demonstrated improvement in their perceived proximity to their health-related and walking goals (L = 1.19, p < .001), the rates of change were significantly greater in the intervention group (β = −.30, p < .05). Our results demonstrate that this physical activity counseling intervention had a positive impact on self-selected goals over the course of the intervention. PMID:20956844

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

An Assessment of Civil Tiltrotor Concept of Operations in the Next Generation Air Transportation System

NASA Technical Reports Server (NTRS)

Chung, William W.; Salvano, Dan; Rinehart, David; Young, Ray; Cheng, Victor; Lindsey, James

2012-01-01

Based on a previous Civil Tiltrotor (CTR) National Airspace System (NAS) performance analysis study, CTR operations were evaluated over selected routes and terminal airspace configurations assuming noninterference operations (NIO) and runway-independent operations (RIO). This assessment aims to further identify issues associated with these concepts of operations (ConOps), and their dependency on the airspace configuration and interaction with conventional fixed-wing traffic. Safety analysis following a traditional Safety Management System (SMS) methodology was applied to CTR-unique departure and arrival failures in the selected airspace to identify any operational and certification issues. Additional CTR operational cases were then developed to get a broader understanding of issues and gaps that will need to be addressed in future CTR operational studies. Finally, needed enhancements to National Airspace System performance analysis tools were reviewed, and recommendations were made on improvements in these tools that are likely to be required to support future progress toward CTR fleet operations in the Next Generation Air Transportation System (NextGen).

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

PubMed

O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

2018-03-01

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

Utility of the advanced chronic kidney disease patient management tools: case studies.

PubMed

Patwardhan, Meenal B; Matchar, David B; Samsa, Gregory P; Haley, William E

2008-01-01

Appropriate management of advanced chronic kidney disease (CKD) delays or limits its progression. The Advanced CKD Patient Management Toolkit was developed using a process-improvement technique to assist patient management and address CKD-specific management issues. We pilot tested the toolkit in 2 community nephrology practices, assessed the utility of individual tools, and evaluated the impact on conformance to an advanced CKD guideline through patient chart abstraction. Tool use was distinct in the 2 sites and depended on the site champion's involvement, the extent of process reconfiguration demanded by a tool, and its perceived value. Baseline conformance varied across guideline recommendations (averaged 54%). Posttrial conformance increased in all clinical areas (averaged 59%). Valuable features of the toolkit in real-world settings were its ability to: facilitate tool selection, direct implementation efforts in response to a baseline performance audit, and allow selection of tool versions and customizing them. Our results suggest that systematically created, multifaceted, and customizable tools can promote guideline conformance.

Resource atlases for multi-atlas brain segmentations with multiple ontology levels based on T1-weighted MRI.

PubMed

Wu, Dan; Ma, Ting; Ceritoglu, Can; Li, Yue; Chotiyanonta, Jill; Hou, Zhipeng; Hsu, John; Xu, Xin; Brown, Timothy; Miller, Michael I; Mori, Susumu

2016-01-15

Technologies for multi-atlas brain segmentation of T1-weighted MRI images have rapidly progressed in recent years, with highly promising results. This approach, however, relies on a large number of atlases with accurate and consistent structural identifications. Here, we introduce our atlas inventories (n=90), which cover ages 4-82years with unique hierarchical structural definitions (286 structures at the finest level). This multi-atlas library resource provides the flexibility to choose appropriate atlases for various studies with different age ranges and structure-definition criteria. In this paper, we describe the details of the atlas resources and demonstrate the improved accuracy achievable with a dynamic age-matching approach, in which atlases that most closely match the subject's age are dynamically selected. The advanced atlas creation strategy, together with atlas pre-selection principles, is expected to support the further development of multi-atlas image segmentation. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of genetic selection on production parameters of single comb White Leghorn hens.

PubMed

Jones, D R; Anderson, K E; Davis, G S

2001-08-01

Four commercial table egg genetic stocks consisting of the Ottawa Control Strains 5, 7, and 10 (CS5, CS7, and CS10) and the 1993 H&N "Nick Chick" (CCS) were housed in the same environment and compared for production characteristics. These birds were housed in an environmentally controlled laying facility with trideck cages. Feed consumption, egg production, and mortality were monitored daily and compiled every 28 d. The study was conducted for two egg production cycles, including the molt period. Body weight was progressively lower for the more modern strains with CS5 being the heaviest and CCS maintaining the smallest body weight throughout the production periods. The CCS had the highest (P < 0.0001) hen-day production rate, which resulted in the greatest daily egg mass among the strains. The CCS consumed the greatest amount of feed and exhibited the highest gross egg income among the strains. We concluded that genetic selection has improved production parameters in commercial layers as determined by measurements in this study.

Mefloquine improved progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus.

PubMed

Beppu, Minako; Kawamoto, Michi; Nukuzuma, Souichi; Kohara, Nobuo

2012-01-01

We describe a case of a 67-year-old man with systemic lupus erythematosus who presented with progressive left hemiplegia. Although the cerebral spinal fluid (CSF) polymerase chain reaction (PCR) for the JC virus was negative, a brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). The tapering of prednisone and the use of cidofovir could not arrest the disease progression. Administration of mefloquine stopped the extension of the lesion, and resulted in obvious clinical improvement. The CSF nested PCR for the JC virus also became negative. This widely used drug should be tried for the treatment of non-HIV PML.

Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule.

PubMed

Bezzina, G; Body, S; Cheung, T H C; Hampson, C L; Bradshaw, C M; Glennon, J C; Szabadi, E

2015-02-01

5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. The effects of the 5-HT2C receptor agonist Ro-600175 ((αS)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m-chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behaviour, 'mathematical principles of reinforcement'. Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. Ro-600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased δ (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1-carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5-HT1B receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT2A receptor antagonist. The results are consistent with the hypothesis that the effect of the 5-HT2C receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer.

Topical issues in unrelated donor haematopoietic stem cell transplants: a report from a workshop convened by the Anthony Nolan Trust in London - 2005.

PubMed

Duarte, R F; Pamphilon, D; Cornish, J; Shaw, B E; Samson, D; Craddock, C; Marks, D; Mufti, G J; Powles, R L; Apperley, J F; Madrigal, J A; Goldman, J M

2006-05-01

Over more than three decades, The Anthony Nolan Trust (ANT) has provided an unrelated donor (UD) for over 4000 children and adults lacking a suitable family member donor, and has remained at the forefront of developments in haematopoietic stem cell transplantation (HSCT) and bone marrow register management. These three decades have seen major changes in clinical practice of UD-HSCT, including new indications, increased use of alternative haematopoietic cell sources, significant improvement of the outcome as a result of better support care, less-toxic conditioning regimens, and better donor selection, and expansion to older patients with higher comorbidities. In order to foster our goal of improving UD-HSCT availability and outcome in a progressively more complex clinical scenario, a new initiative from ANT was launched in 2005 to convene an experts workshop to address the topical issues in this field. Four consecutive panels addressed factors influencing donor selection and transplant outcome, the use of cord blood, regulatory and accreditation issues, and future developments in this field. This report summarizes the discussions held in this workshop, which will likely develop into a periodic event where transplant clinicians, scientists and registry members will meet to share their experience and vision in the field of UD-HSCT.

Excess black mortality in the United States and in selected black and white high-poverty areas, 1980-2000.

PubMed

Geronimus, Arline T; Bound, John; Colen, Cynthia G

2011-04-01

Black working-aged residents of urban high-poverty areas suffered severe excess mortality in 1980 and 1990. Our goal in this study was to determine whether this trend persisted in 2000. We analyzed death certificate and census data to estimate age-standardized all-cause and cause-specific mortality among 16- to 64-year-old Blacks and Whites nationwide and in selected urban and rural high-poverty areas. Urban men's mortality rate estimates peaked in 1990 and declined between 1990 and 2000 back to or below 1980 levels. Evidence of excess mortality declines among urban or rural women and among rural men was modest, with some increases. Between 1980 and 2000, there was little decline in chronic disease mortality among men and women in most areas, and in some instances there were increases. In 2000, despite improved economic conditions, working-age residents of the study areas still died disproportionately of early onset of chronic disease, suggesting an entrenched burden of disease and unmet health care needs. The lack of consistent improvement in death rates among working-age residents of high-poverty areas since 1980 necessitates reflection and concerted action given that sustainable progress has been elusive for this age group.

National nursing strategies in seven countries of the Region of the Americas: issues and impact.

PubMed

Shasanmi, Rebecca O; Kim, Esther M; Cassiani, Silvia Helena De Bortoli

2015-07-01

To identify and examine the current national nursing strategies and policy impact of workforce development regarding human resources for health in seven selected countries in the Region of the Americas: Argentina, Canada, Costa Rica, Jamaica, Mexico, Peru, and the United States. A review of available literature was conducted to identify publicly-available documents that describe the general backdrop of nursing human resources in these seven countries. A keyword search of PubMed was supplemented by searches of websites maintained by Ministries of Health and nursing organizations. Inclusion criteria limited documents to those published in 2008-2013 that discussed or assessed situational issues and/or progress surrounding the nursing workforce. Nursing human resources for health is progressing. Canada, Mexico, and the United States have stronger nursing leadership in place and multisectoral policies in workforce development. Jamaica shows efforts among the Caribbean countries to promote collaborative practices in research. The three selected countries in Central and South America championed networks to revive nursing education. Yet, overall challenges limit the opportunities to impact public health. The national nursing strategies prioritized multisectoral collaboration, professional competencies, and standardized educational systems, with some countries underscoring the need to align policies with efforts to promote nursing leadership, and others, focusing on expanding the scope of practice to improve health care delivery. While each country wrestles with its specific context, all require proper leadership, multisectoral collaboration, and appropriate resources to educate, train, and empower nurses to be at the forefront.

"Peer workers/health counselors": a new label for a labeled population. A work-in-progress which may not progress.

PubMed

Einstein, Stan

2012-04-01

The relatively new labels, "peer workers," "peer health counselors," etc., are explored in terms of a selected number of their implications--few, if any, of which have been or are positive for this targeted population.

Successful Career Progression: Exploratory Findings from a Study of Selected Occupations.

ERIC Educational Resources Information Center

O'Shea, Daniel P.; Betsinger, Alicia M.; King, Christopher T.

A study examined the career progression of individuals in the following occupations: registered nurse; physical therapist; medical laboratory technologist; paramedic; ranked corrections officer; dental hygienist; electronic technician; pipefitter/plumber; social worker; and auto body shop manager. Researchers conducted face-to-face interviews in…

Diversity and inclusiveness in large scientific collaborations

NASA Astrophysics Data System (ADS)

Lucatello, Sara; Diamond-Stanic, Aleksandar

2017-06-01

Considerable progress has been made in the past decade to increase diversity in astronomy, and in particular to reach a 'critical mass' of women. It is however important to realize that this progress has mainly been the result of the selective inclusion of women from more privileged backgrounds.

The Progress of US Hospitals in Addressing Community Health Needs.

PubMed

Cramer, Geri Rosen; Singh, Simone R; Flaherty, Stephen; Young, Gary J

2017-02-01

To identify how US tax-exempt hospitals are progressing in regard to community health needs assessment (CHNA) implementation following the Patient Protection and Affordable Care Act. We analyzed data on more than 1500 tax-exempt hospitals in 2013 to assess patterns in CHNA implementation and to determine whether a hospital's institutional and community characteristics are associated with greater progress. Our findings show wide variation among hospitals in CHNA implementation. Hospitals operating as part of a health system as well as hospitals participating in a Medicare accountable care organization showed greater progress in CHNA implementation whereas hospitals serving a greater proportion of uninsured showed less progress. We also found that hospitals reporting the highest level of CHNA implementation progress spent more on community health improvement. Hospitals widely embraced the regulations to perform a CHNA. Less is known about how hospitals are moving forward to improve population health through the implementation of programs to meet identified community needs.

Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

PubMed

Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J

2017-12-12

To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

PubMed

van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

2017-03-07

North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

Nudging oligodendrocyte intrinsic signaling to remyelinate and repair: Estrogen receptor ligand effects.

PubMed

Khalaj, Anna J; Hasselmann, Jonathan; Augello, Catherine; Moore, Spencer; Tiwari-Woodruff, Seema K

2016-06-01

Demyelination in multiple sclerosis (MS) leads to significant, progressive axonal and neuronal degeneration. Currently existing immunosuppressive and immunomodulatory therapies alleviate MS symptoms and slow, but fail to prevent or reverse, disease progression. Restoration of damaged myelin sheath by replenishment of mature oligodendrocytes (OLs) should not only restore saltatory axon conduction, but also provide a major boost to axon survival. Our previous work has shown that therapeutic treatment with the modestly selective generic estrogen receptor (ER) β agonist diarylpropionitrile (DPN) confers functional neuroprotection in a chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS by stimulating endogenous remyelination. Recently, we found that the more potent, selective ERβ agonist indazole-chloride (Ind-Cl) improves clinical disease and motor performance. Importantly, electrophysiological measures revealed improved corpus callosal conduction and reduced axon refractoriness. This Ind-Cl treatment-induced functional remyelination was attributable to increased OL progenitor cell (OPC) and mature OL numbers. At the intracellular signaling level, transition of early to late OPCs requires ERK1/2 signaling, and transition of immature to mature OLs requires mTOR signaling; thus, the PI3K/Akt/mTOR pathway plays a major role in the late stages of OL differentiation and myelination. Indeed, therapeutic treatment of EAE mice with various ERβ agonists results in increased brain-derived neurotrophic factor (BDNF) and phosphorylated (p) Akt and p-mTOR levels. It is notable that while DPN's neuroprotective effects occur in the presence of peripheral and central inflammation, Ind-Cl is directly neuroprotective, as demonstrated by remyelination effects in the cuprizone-induced demyelination model, as well as immunomodulatory. Elucidating the mechanisms by which ER agonists and other directly remyelinating agents modulate endogenous OPC and OL regulatory signaling is critical to the development of effective remyelinating drugs. The discovery of signaling targets to induce functional remyelination will valuably contribute to the treatment of demyelinating neurological diseases, including MS, stroke, and traumatic brain and spinal cord injury. Published by Elsevier Ltd.

Nudging Oligodendrocyte Intrinsic Signaling to Remyelinate and Repair: Estrogen Receptor Ligand Effects

PubMed Central

Khalaj, Anna J.; Hasselmann, Jonathan; Augello, Catherine; Moore, Spencer; Tiwari-Woodruff, Seema K.

2017-01-01

Demyelination in multiple sclerosis (MS) leads to significant, progressive axonal and neuronal degeneration. Currently existing immunosuppressive and immunomodulatory therapies alleviate MS symptoms and slow, but fail to prevent or reverse, disease progression. Restoration of damaged myelin sheath by replenishment of mature oligodendrocytes (OLs) should not only restore saltatory axon conduction, but also provide a major boost to axon survival. Our previous work has shown that therapeutic treatment with the modestly selective generic estrogen receptor (ER) β agonist diarylpropionitrile (DPN) confers functional neuroprotection in a chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS by stimulating endogenous myelination. Recently, we found that the more potent, selective ERβ agonist indazole-chloride (Ind-Cl) improves clinical disease and motor performance. Importantly, electrophysiological measures revealed improved corpus callosal conduction and reduced axon refractoriness. This Ind-Cl treatment-induced functional remyelination was attributable to increased OL progenitor cell (OPC) and mature OL numbers. At the intracellular signaling level, transition of early to late OPCs requires Erk1/2 signaling, and transition of immature to mature OLs requires mTOR signaling; thus, the PI3K/Akt/mTOR pathway plays a major role in the late stages of OL differentiation and myelination. Indeed, therapeutic treatment of EAE mice with various ERβ agonists results in increased brain-derived neurotrophic factor (BDNF) and phosphorylated (p) Akt and p-mTOR levels. It is notable that while DPN’s neuroprotective effects occur in the presence of peripheral and central inflammation, Ind-Cl is directly neuroprotective, as demonstrated by remyelination effects in the cuprizone-induced demyelination model, as well as anti-inflammatory. Elucidating the mechanisms by which ER agonists and other directly remyelinating agents modulate endogenous OPC and OL regulatory signaling is critical to the development of effective remyelinating drugs. The discovery of signaling targets to induce functional remyelination will valuably contribute to the treatment of demyelinating neurological diseases, including MS, stroke, and traumatic brain and spinal cord injury. PMID:26776441

SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer.

PubMed

van Hazel, Guy A; Heinemann, Volker; Sharma, Navesh K; Findlay, Michael P N; Ricke, Jens; Peeters, Marc; Perez, David; Robinson, Bridget A; Strickland, Andrew H; Ferguson, Tom; Rodríguez, Javier; Kröning, Hendrik; Wolf, Ido; Ganju, Vinod; Walpole, Euan; Boucher, Eveline; Tichler, Thomas; Shacham-Shmueli, Einat; Powell, Alex; Eliadis, Paul; Isaacs, Richard; Price, David; Moeslein, Fred; Taieb, Julien; Bower, Geoff; Gebski, Val; Van Buskirk, Mark; Cade, David N; Thurston, Kenneth; Gibbs, Peter

2016-05-20

SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. Chemotherapy-naïve patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade ≥ 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies. © 2016 by American Society of Clinical Oncology.

Algorithmic methods to infer the evolutionary trajectories in cancer progression

PubMed Central

Graudenzi, Alex; Ramazzotti, Daniele; Sanz-Pamplona, Rebeca; De Sano, Luca; Mauri, Giancarlo; Moreno, Victor; Antoniotti, Marco; Mishra, Bud

2016-01-01

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the “selective advantage” relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc’s ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses. PMID:27357673

Personalized Progress Charts: An Effective Motivation for Reluctant Readers.

ERIC Educational Resources Information Center

Webre, Elizabeth C.

Progress charts are an effective means of dramatizing student effort and improvement in reading and are especially important for remedial reading students, who need concrete evidence of progress. Remedial reading students often need extrinsic reward, and since reading is a complex act, progress charts lend themselves to the element of reward and…

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…

Evaluation of water, sanitation and hygiene program outcomes shows knowledge-behavior gaps in Coast Province, Kenya.

PubMed

Schlegelmilch, Michael Paul; Lakhani, Amyn; Saunders, Leslie Duncan; Jhangri, Gian Singh

2016-01-01

Water related diseases constitute a significant proportion of the burden of disease in Kenya. Water, sanitation and hygiene (WASH) programs are in operation nation-wide to address these challenges. This study evaluated the impact of the Sombeza Water and Sanitation Improvement Program (SWASIP) in Coast Province, Kenya. This study is a cluster randomized, follow-up evaluation that compared baseline (2007) to follow-up (2013) indicators from 250 households. Twenty-five villages were selected with probability proportional to size sampling, and ten households were selected randomly from each village. Follow-up data were collected by in-person interviews using pre-tested questionnaires, and analyzed to compare indicators collected at baseline. Cross-sectional results from the follow-up data were also reported. Statistically significant improvements from baseline were observed in the proportions of respondents with latrine access at home, who washed their hands after defecation, who treated their household drinking water and the average time to collect water in the dry season. However, this study also observed significant decreases in the proportion of respondents who washed their hands before preparing their food, or feeding their children, and after attending to a child who has defecated. The analysis also revealed a knowledge-behavior gap in WASH behaviors. SWASIP contributed to improvements from baseline, but further progress still needs to be seen. The findings challenge the assumption that providing infrastructure and knowledge will result in behavior change. Further understanding of specific, non-knowledge predictors of WASH related behavior is needed.

Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial.

PubMed

O'Leary, Daniel H; Reuwer, Anne Q; Nissen, Steven E; Després, Jean-Pierre; Deanfield, John E; Brown, Michael W; Zhou, Rong; Zabbatino, Salvatore M; Job, Bernard; Kastelein, John J P; Visseren, Frank L J

2011-07-01

The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese. A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima-media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima-media thickness from baseline to month 30 was 0.010 ± 0.095 mm in the rimonabant group and 0.012 ± 0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005 ± 0.042 mm for the rimonabant-treated group and 0.007 ± 0.043 mm for the placebo-treated group (p=0.45). There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima-media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome. Clinical trial registration information clinicaltrials.gov Identifier: NCT00228176.

Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress

PubMed Central

Olsovska, Katarina; Kovar, Marek; Brestic, Marian; Zivcak, Marek; Slamka, Pavol; Shao, Hong Bo

2016-01-01

Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID:27551283

The 24th Annual Prostate Cancer Foundation scientific retreat report.

PubMed

Miyahira, Andrea K; Soule, Howard R

2018-05-15

The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5-7, 2017, at the Omni Shoreham Hotel in Washington, DC. The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment. Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA-targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer. This article reviews the research presented at the PCF Scientific Retreat, in order to improve understanding of the current state of prostate cancer research, encourage discourse and exchange of novel ideas, and stimulate new basic, translational, and clinical research that will ultimately improve the lives of patients. © 2018 Wiley Periodicals, Inc.

Streamlining Appointment, Promotion, and Tenure Procedures to Promote Early-Career Faculty Success.

PubMed

Smith, Shannon B; Hollerbach, Ann; Donato, Annemarie Sipkes; Edlund, Barbara J; Atz, Teresa; Kelechi, Teresa J

2016-01-01

A critical component of the progression of a successful academic career is being promoted in rank. Early-career faculty are required to have an understanding of appointment, promotion, and tenure (APT) guidelines, but many factors often impede this understanding, thwarting a smooth and planned promotion pathway for professional advancement. This article outlines the steps taken by an APT committee to improve the promotion process from instructor to assistant professor. Six sigma's DMAIC improvement model was selected as the guiding operational framework to remove variation in the promotion process. After faculty handbook revisions were made, several checklists developed, and a process review rubric was implemented; recently promoted faculty were surveyed on satisfaction with the process. Faculty opinions captured in the survey suggest increased transparency in the process and perceived support offered by the APT committee. Positive outcomes include a strengthened faculty support framework, streamlined promotion processes, and improved faculty satisfaction. Changes to the APT processes resulted in an unambiguous and standardized pathway for successful promotion. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinal stimulation strategies to restore vision: Fundamentals and systems.

PubMed

Yue, Lan; Weiland, James D; Roska, Botond; Humayun, Mark S

2016-07-01

Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimization of Deep Drilling Performance - Development and Benchmark Testing of Advanced Diamond Product Drill Bits & HP/HT Fluids to Significantly Improve Rates of Penetration

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

Alan Black; Arnis Judzis

2005-09-30

This document details the progress to date on the OPTIMIZATION OF DEEP DRILLING PERFORMANCE--DEVELOPMENT AND BENCHMARK TESTING OF ADVANCED DIAMOND PRODUCT DRILL BITS AND HP/HT FLUIDS TO SIGNIFICANTLY IMPROVE RATES OF PENETRATION contract for the year starting October 2004 through September 2005. The industry cost shared program aims to benchmark drilling rates of penetration in selected simulated deep formations and to significantly improve ROP through a team development of aggressive diamond product drill bit--fluid system technologies. Overall the objectives are as follows: Phase 1--Benchmark ''best in class'' diamond and other product drilling bits and fluids and develop concepts for amore » next level of deep drilling performance; Phase 2--Develop advanced smart bit-fluid prototypes and test at large scale; and Phase 3--Field trial smart bit--fluid concepts, modify as necessary and commercialize products. As of report date, TerraTek has concluded all Phase 1 testing and is planning Phase 2 development.« less

Refining each process step to accelerate the development of biorefineries

DOE PAGES

Chandra, Richard P.; Ragauskas, Art J.

2016-06-21

Research over the past decade has been mainly focused on overcoming hurdles in the pretreatment, enzymatic hydrolysis, and fermentation steps of biochemical processing. Pretreatments have improved significantly in their ability to fractionate and recover the cellulose, hemicellulose, and lignin components of biomass while producing substrates containing carbohydrates that can be easily broken down by hydrolytic enzymes. There is a rapid movement towards pretreatment processes that incorporate mechanical treatments that make use of existing infrastructure in the pulp and paper industry, which has experienced a downturn in its traditional markets. Enzyme performance has also made great strides with breakthrough developments inmore » nonhydrolytic protein components, such as lytic polysaccharide monooxygenases, as well as the improvement of enzyme cocktails.The fermentability of pretreated and hydrolyzed sugar streams has been improved through strategies such as the use of reducing agents for detoxification, strain selection, and strain improvements. Although significant progress has been made, tremendous challenges still remain to advance each step of biochemical conversion, especially when processing woody biomass. In addition to technical and scale-up issues within each step of the bioconversion process, biomass feedstock supply and logistics challenges still remain at the forefront of biorefinery research.« less

Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.

PubMed

Pommergaard, Hans-Christian; Rostved, Andreas Arendtsen; Adam, René; Thygesen, Lau Caspar; Salizzoni, Mauro; Gómez Bravo, Miguel Angel; Cherqui, Daniel; De Simone, Paolo; Boudjema, Karim; Mazzaferro, Vincenzo; Soubrane, Olivier; García-Valdecasas, Juan Carlos; Fabregat Prous, Joan; Pinna, Antonio D; O'Grady, John; Karam, Vincent; Duvoux, Christophe; Rasmussen, Allan

2018-05-01

Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096. © 2018 Steunstichting ESOT.

Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers

PubMed Central

Xue, Shenghui; Qiao, Jingjuan; Pu, Fan; Cameron, Mathew; Yang, Jenny J.

2014-01-01

Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd3+ with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd3+ MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications. PMID:23335551

Multi-clues image retrieval based on improved color invariants

NASA Astrophysics Data System (ADS)

Liu, Liu; Li, Jian-Xun

2012-05-01

At present, image retrieval has a great progress in indexing efficiency and memory usage, which mainly benefits from the utilization of the text retrieval technology, such as the bag-of-features (BOF) model and the inverted-file structure. Meanwhile, because the robust local feature invariants are selected to establish BOF, the retrieval precision of BOF is enhanced, especially when it is applied to a large-scale database. However, these local feature invariants mainly consider the geometric variance of the objects in the images, and thus the color information of the objects fails to be made use of. Because of the development of the information technology and Internet, the majority of our retrieval objects is color images. Therefore, retrieval performance can be further improved through proper utilization of the color information. We propose an improved method through analyzing the flaw of shadow-shading quasi-invariant. The response and performance of shadow-shading quasi-invariant for the object edge with the variance of lighting are enhanced. The color descriptors of the invariant regions are extracted and integrated into BOF based on the local feature. The robustness of the algorithm and the improvement of the performance are verified in the final experiments.

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

Predication of different stages of Alzheimer's disease using neighborhood component analysis and ensemble decision tree.

PubMed

Jin, Mingwu; Deng, Weishu

2018-05-15

There is a spectrum of the progression from healthy control (HC) to mild cognitive impairment (MCI) without conversion to Alzheimer's disease (AD), to MCI with conversion to AD (cMCI), and to AD. This study aims to predict the different disease stages using brain structural information provided by magnetic resonance imaging (MRI) data. The neighborhood component analysis (NCA) is applied to select most powerful features for prediction. The ensemble decision tree classifier is built to predict which group the subject belongs to. The best features and model parameters are determined by cross validation of the training data. Our results show that 16 out of a total of 429 features were selected by NCA using 240 training subjects, including MMSE score and structural measures in memory-related regions. The boosting tree model with NCA features can achieve prediction accuracy of 56.25% on 160 test subjects. Principal component analysis (PCA) and sequential feature selection (SFS) are used for feature selection, while support vector machine (SVM) is used for classification. The boosting tree model with NCA features outperforms all other combinations of feature selection and classification methods. The results suggest that NCA be a better feature selection strategy than PCA and SFS for the data used in this study. Ensemble tree classifier with boosting is more powerful than SVM to predict the subject group. However, more advanced feature selection and classification methods or additional measures besides structural MRI may be needed to improve the prediction performance. Copyright © 2018 Elsevier B.V. All rights reserved.

Alternative Approach to Teaching Veterinary Anatomy: A Progress Report

ERIC Educational Resources Information Center

Hullinger, Ronald; Render, Gary F.

1975-01-01

Students in microscopic anatomy at Purdue University School of Veterinary Medicine selected a self-directed or teacher-directed approach to the course. Adoption of the experimental approach described here increased faculty time for evaluating student progress but was supportive of student development particularly in cognitive skills and affective…

Selected Progressive Competencies for Education of the Gifted.

ERIC Educational Resources Information Center

Daniels, Roberta R.; And Others

Progressive competencies were identified for gifted students in grades kindergarten through 12 as a result of a survey of over 600 administrators, classroom teachers, and teachers of the gifted. Competencies were identified for four levels of development in the following six specific skill areas: creativity, affective development, academic…

Teaching Self-Control to Small Groups of Dually Diagnosed Adults.

ERIC Educational Resources Information Center

Dixon, Mark R.; Holcomb, Sharon

2000-01-01

A study used a progressive delay procedure to teach self-control to six adults with mental retardation. At baseline, participants chose an immediate smaller reinforcer rather than a larger delayed reinforcer. Progressive increases in work requirements for gaining access to a larger reinforcer resulted in participants selecting larger delayed…

Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.

PubMed

Su, Zhao-Zhong; Sarkar, Devanand; Emdad, Luni; Duigou, Gregory J; Young, Charles S H; Ware, Joy; Randolph, Aaron; Valerie, Kristoffer; Fisher, Paul B

2005-01-25

One impediment to effective cancer-specific gene therapy is the rarity of regulatory sequences targeting gene expression selectively in tumor cells. Although many tissue-specific promoters are recognized, few cancer-selective gene promoters are available. Progression-elevated gene-3 (PEG-3) is a rodent gene identified by subtraction hybridization that displays elevated expression as a function of transformation by diversely acting oncogenes, DNA damage, and cancer cell progression. The promoter of PEG-3, PEG-Prom, displays robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Whereas GFP expression, when under the control of a CMV promoter, is detected in both normal and cancer cells, when GFP is expressed under the control of the PEG-Prom, cancer-selective expression is evident. Mutational analysis identifies the AP-1 and PEA-3 transcription factors as primary mediators of selective, cancer-specific expression of the PEG-Prom. Synthesis of apoptosis-inducing genes, under the control of the CMV promoter, inhibits the growth of both normal and cancer cells, whereas PEG-Prom-mediated expression of these genes kills only cancer cells and spares normal cells. The efficacy of the PEG-Prom as part of a cancer gene therapeutic regimen is further documented by in vivo experiments in which PEG-Prom-controlled expression of an apoptosis-inducing gene completely inhibited prostate cancer xenograft growth in nude mice. These compelling observations indicate that the PEG-Prom, with its cancer-specific expression, provides a means of selectively delivering genes to cancer cells, thereby providing a crucial component in developing effective cancer gene therapies.

Dissociation of Progressive Dopaminergic Neuronal Death and Behavioral Impairments by Bax Deletion in a Mouse Model of Parkinson's Diseases

PubMed Central

Kim, Tae Woo; Moon, Younghye; Kim, Kyungjin; Lee, Jeong Eun; Koh, Hyun Chul; Rhyu, Im Joo; Kim, Hyun; Sun, Woong

2011-01-01

Parkinson's disease (PD) is a common, late-onset movement disorder with selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Although the neurotoxin 6-hydroxydopamine (6-OHDA) has been used to induce progressive degeneration of DA neurons in various animal models of PD, the precise molecular pathway and the impact of anti-apoptotic treatment on this neurodegeneration are less understood. Following a striatal injection of 6-OHDA, we observed atrophy and progressive death of DA neurons in wild-type mice. These degenerating DA neurons never exhibited signs of apoptosis (i.e., caspase-3 activation and cytoplasmic release of cytochrome C), but rather show nuclear translocation of apoptosis-inducing factor (AIF), a hallmark of regulated necrosis. However, mice with genetic deletion of the proapoptotic gene Bax (Bax-KO) exhibited a complete absence of 6-OHDA-induced DA neuron death and nuclear translocation of AIF, indicating that 6-OHDA-induced DA neuronal death is mediated by Bax-dependent AIF activation. On the other hand, DA neurons that survived in Bax-KO mice exhibited marked neuronal atrophy, without significant improvement of PD-related behavioral deficits. These findings suggest that anti-apoptotic therapy may not be sufficient for PD treatment, and the prevention of Bax-independent neuronal atrophy may be an important therapeutic target. PMID:22043283

Outcome of the acute glomerular injury in proliferative lupus nephritis

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

Chagnac, A.; Kiberd, B.A.; Farinas, M.C.

1989-09-01

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR weremore » modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.« less

Experimental procedure for measuring and comparing head-neck-trunk posture and movements caused by different progressive addition lens designs.

PubMed

Mateo, B; Porcar-Seder, R; Solaz, J S; Dürsteler, J C

2010-07-01

This study demonstrates that appropriate measurement procedures can detect differences in head movement in a near reading task when using three different progressive addition lenses (PALs). The movements were measured using an anatomical reference system with a biomechanical rationale. This reference system was capable of representing rotations for comparing head flexion relative to trunk, head flexion relative to neck, head rotation relative to trunk and trunk flexion. The subject sample comprised 31 volunteers and three PAL designs with different viewing zones were selected. Significant differences were found between the lenses for three of the seven movement parameters examined. The differences occurred for both vertical and horizontal head movements and could be attributed to aspects of the PAL design. The measurement of the complete kinematic trunk-neck-head chain improved the number of differences that were found over those in previous studies. STATEMENT OF RELEVANCE: The study proposes a methodology based on a biomechanical rationale able to differentiate head-neck-trunk posture and movements caused by different progressive addition lens designs with minimum invasiveness. This methodology could also be applied to analyse the ergonomics of other devices that restrict the user's field of view, such as helmets, personal protective equipment or helmet-mounted displays for pilots. This analysis will allow designers to optimise designs offering higher comfort and performance.

Trait-specific long-term consequences of genomic selection in beef cattle.

PubMed

de Rezende Neves, Haroldo Henrique; Carvalheiro, Roberto; de Queiroz, Sandra Aidar

2018-02-01

Simulation studies allow addressing consequences of selection schemes, helping to identify effective strategies to enable genetic gain and maintain genetic diversity. The aim of this study was to evaluate the long-term impact of genomic selection (GS) in genetic progress and genetic diversity of beef cattle. Forward-in-time simulation generated a population with pattern of linkage disequilibrium close to that previously reported for real beef cattle populations. Different scenarios of GS and traditional pedigree-based BLUP (PBLUP) selection were simulated for 15 generations, mimicking selection for female reproduction and meat quality. For GS scenarios, an alternative selection criterion was simulated (wGBLUP), intended to enhance long-term gains by attributing more weight to favorable alleles with low frequency. GS allowed genetic progress up to 40% greater than PBLUP, for female reproduction and meat quality. The alternative criterion wGBLUP did not increase long-term response, although allowed reducing inbreeding rates and loss of favorable alleles. The results suggest that GS outperforms PBLUP when the selected trait is under less polygenic background and that attributing more weight to low-frequency favorable alleles can reduce inbreeding rates and loss of favorable alleles in GS.

Honoring Progress: An Update on the NGA Center Honor States. Volume 1, Issue 4

ERIC Educational Resources Information Center

Hartney, Michael, Ed.

2007-01-01

This bimonthly newsletter provides information about the progress of the Honor States Grant Program, a governor-led effort to improve college--and work-ready graduation rates. This issue explores efforts by governors and state policymakers to experiment with alternative compensation policies that can improve teacher quality. Compensation…

Strategies To Improve Young People's Access to, and Their Progression within, Initial Vocational Training.

ERIC Educational Resources Information Center

Banks, John

Strategies to improve disadvantaged young people's access to and progression within initial vocational training (VT) were identified through a study of relevant experiences within the European Union's member states. The study, which was based on national reports from each country, focused on the following topics: identifying the challenges and…

All That Glitters Is Not Gold: School Reform in Charlotte-Mecklenburg.

ERIC Educational Resources Information Center

Smith, Stephen Samuel; Mickelson, Roslyn Arlin

2000-01-01

Compared the progress of the Charlotte-Mecklenburg school district, North Carolina, in improving student outcomes with progress in two other North Carolina school districts and the entire state. There was no evidence that the sweeping program of school reform in Charlotte-Mecklenburg improved academic outcomes except in a few advanced placement…

Progress in the improved lattice calculation of direct CP-violation in the Standard Model

NASA Astrophysics Data System (ADS)

Kelly, Christopher

2018-03-01

We discuss the ongoing effort by the RBC & UKQCD collaborations to improve our lattice calculation of the measure of Standard Model direct CP violation, ɛ', with physical kinematics. We present our progress in decreasing the (dominant) statistical error and discuss other related activities aimed at reducing the systematic errors.

Proteomic profiling for plasma biomarkers of tuberculosis progression.

PubMed

Liu, Qiuyue; Pan, Liping; Han, Fen; Luo, Baojian; Jia, Hongyan; Xing, Aiying; Li, Qi; Zhang, Zongde

2018-06-05

Severe pulmonary tuberculosis (STB) is a life‑threatening condition with high economic and social burden. The present study aimed to screen for distinct proteins in different stages of TB and identify biomarkers for a better understanding of TB progression and pathogenesis. Blood samples were obtained from 81 patients with STB, 80 with mild TB (MTB) and 50 healthy controls. Differentially expressed proteins were identified using liquid chromatography‑tandem mass spectrometry‑based label‑free quantitative proteomic analysis. Functional and pathway enrichment analyses were performed for the identified proteins. The expression of potential biomarkers was further validated by western blot analysis and enzyme‑linked immunosorbent assays. The accuracy, sensitivity and specificity for selected protein biomarkers in diagnosing STB were also evaluated. A total of 1,011 proteins were identified in all three groups, and 153 differentially expressed proteins were identified in patients with STB. These proteins were involved in 'cellular process', 'response to stimulus', 'apoptotic process', 'immune system process' and 'select metabolic process'. Significant differences in protein expression were detected in α‑1‑acid glycoprotein 2 (ORM2), interleukin‑36α (IL‑36α), S100 calcium binding protein A9 (S100‑A9), superoxide dismutase (SOD)1 in the STB group, compared with the MTB and control groups. The combination of plasma ORM2, IL‑36α, S100A9 and SOD1 levels achieved 90.00% sensitivity and 92.16% specificity to discriminate between patients with STB and MTB, and 89.66% sensitivity and 98.9% specificity to discriminate between patients with STB and healthy controls. ORM2, S100A9, IL‑36α and SOD1 were associated with the development of TB, and have the potential to distinguish between different stages of TB. Differential protein expression during disease progression may improve the current understanding of STB pathogenesis.

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

PubMed

Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

2014-01-01

To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. Copyright © 2013. Published by Elsevier Inc.

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

PubMed Central

Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

2015-01-01

Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. PMID:24239753

34 CFR 200.50 - SEA review of LEA progress.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false SEA review of LEA progress. 200.50 Section 200.50... Basic Programs Operated by Local Educational Agencies Lea and School Improvement § 200.50 SEA review of LEA progress. (a) State review. (1) An SEA must annually review the progress of each LEA in its State...

34 CFR 200.50 - SEA review of LEA progress.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false SEA review of LEA progress. 200.50 Section 200.50... Basic Programs Operated by Local Educational Agencies Lea and School Improvement § 200.50 SEA review of LEA progress. (a) State review. (1) An SEA must annually review the progress of each LEA in its State...

34 CFR 200.50 - SEA review of LEA progress.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false SEA review of LEA progress. 200.50 Section 200.50... Basic Programs Operated by Local Educational Agencies Lea and School Improvement § 200.50 SEA review of LEA progress. (a) State review. (1) An SEA must annually review the progress of each LEA in its State...

34 CFR 200.50 - SEA review of LEA progress.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false SEA review of LEA progress. 200.50 Section 200.50... Basic Programs Operated by Local Educational Agencies Lea and School Improvement § 200.50 SEA review of LEA progress. (a) State review. (1) An SEA must annually review the progress of each LEA in its State...

34 CFR 200.50 - SEA review of LEA progress.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false SEA review of LEA progress. 200.50 Section 200.50... Basic Programs Operated by Local Educational Agencies Lea and School Improvement § 200.50 SEA review of LEA progress. (a) State review. (1) An SEA must annually review the progress of each LEA in its State...

Energy access and living standards: some observations on recent trends

NASA Astrophysics Data System (ADS)

Rao, Narasimha D.; Pachauri, Shonali

2017-02-01

A subset of Sustainable Development Goals pertains to improving people’s living standards at home. These include the provision of access to electricity, clean cooking energy, improved water and sanitation. We examine historical progress in energy access in relation to other living standards. We assess regional patterns in the pace of progress and relative priority accorded to these different services. Countries in sub-Saharan Africa would have to undergo unprecedented rates of improvement in energy access in order to achieve the goal of universal electrification by 2030. World over, access to clean cooking fuels and sanitation facilities consistently lag improved water and electricity access by a large margin. These two deprivations are more concentrated among poor countries, and poor people in middle income countries. They are also correlated to health risks faced disproportionately by women. However, some Asian countries have been able to achieve faster progress in electrification at lower income levels compared to industrialized countries’ earlier efforts. These examples offer hope that future efforts need not be constrained by historical rates of progress.

Nuclear Power Plant Mechanical Component Flooding Fragility Experiments Status

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

Pope, C. L.; Savage, B.; Johnson, B.

This report describes progress on Nuclear Power Plant mechanical component flooding fragility experiments and supporting research. The progress includes execution of full scale fragility experiments using hollow-core doors, design of improvements to the Portal Evaluation Tank, equipment procurement and initial installation of PET improvements, designation of experiments exploiting the improved PET capabilities, fragility mathematical model development, Smoothed Particle Hydrodynamic simulations, wave impact simulation device research, and pipe rupture mechanics research.

RDT&E Progress and Plansfor Hexavalent Chromium (Cr6+)

DTIC Science & Technology

2011-05-12

RDT&E Progress and Plans for Hexavalent Chromium (Cr6+) Bruce Sartwell Weapons Systems and Platforms Program Manager E2S2 Conference May 12, 2011...2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE RDT&E Progress and Plansfor Hexavalent Chromium (Cr6+) 5a...Tasks/Projects Surface treatments and soluble inhibitors: 1. Fundamental studies of the Trivalent Chrome Process (TCP) 2. Mechanisms of selected

Beyond the temporal pole: limbic memory circuit in the semantic variant of primary progressive aphasia.

PubMed

Tan, Rachel H; Wong, Stephanie; Kril, Jillian J; Piguet, Olivier; Hornberger, Michael; Hodges, John R; Halliday, Glenda M

2014-07-01

Despite accruing evidence for relative preservation of episodic memory in the semantic variant of primary progressive aphasia (previously semantic dementia), the neural basis for this remains unclear, particularly in light of their well-established hippocampal involvement. We recently investigated the Papez network of memory structures across pathological subtypes of behavioural variant frontotemporal dementia and demonstrated severe degeneration of all relay nodes, with the anterior thalamus in particular emerging as crucial for intact episodic memory. The present study investigated the status of key components of Papez circuit (hippocampus, mammillary bodies, anterior thalamus, cingulate cortex) and anterior temporal cortex using volumetric and quantitative cell counting methods in pathologically-confirmed cases with semantic variant of primary progressive aphasia (n = 8; 61-83 years; three males), behavioural variant frontotemporal dementia with TDP pathology (n = 9; 53-82 years; six males) and healthy controls (n = 8, 50-86 years; four males). Behavioural variant frontotemporal dementia cases with TDP pathology were selected because of the association between the semantic variant of primary progressive aphasia and TDP pathology. Our findings revealed that the semantic variant of primary progressive aphasia and behavioural variant frontotemporal dementia show similar degrees of anterior thalamic atrophy. The mammillary bodies and hippocampal body and tail were preserved in the semantic variant of primary progressive aphasia but were significantly atrophic in behavioural variant frontotemporal dementia. Importantly, atrophy in the anterior thalamus and mild progressive atrophy in the body of the hippocampus emerged as the main memory circuit regions correlated with increasing dementia severity in the semantic variant of primary progressive aphasia. Quantitation of neuronal populations in the cingulate cortices confirmed the selective loss of anterior cingulate von Economo neurons in behavioural variant frontotemporal dementia. We also show that by end-stage these neurons selectively degenerate in the semantic variant of primary progressive aphasia with preservation of neurons in the posterior cingulate cortex. Overall, our findings demonstrate for the first time, severe atrophy, although not necessarily neuronal loss, across all relay nodes of Papez circuit with the exception of the mammillary bodies and hippocampal body and tail in the semantic variant of primary progressive aphasia. Despite the longer disease course in the semantic variant of primary progressive aphasia compared with behavioural variant frontotemporal dementia, we suggest here that the neural preservation of crucial memory relays (hippocampal→mammillary bodies and posterior cingulate→hippocampus) likely reflects the conservation of specific episodic memory components observed in most patients with semantic variant of primary progressive aphasia. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An application specific integrated circuit based multi-anode microchannel array readout system

NASA Technical Reports Server (NTRS)

Smeins, Larry G.; Stechman, John M.; Cole, Edward H.

1991-01-01

Size reduction of two new multi-anode microchannel array (MAMA) readout systems is described. The systems are based on two analog and one digital application specific integrated circuits (ASICs). The new readout systems reduce volume over previous discrete designs by 80 percent while improving electrical performance on virtually every significant parameter. Emphasis is made on the packaging used to achieve the volume reduction. Surface mount technology (SMT) is combined with modular construction for the analog portion of the readout. SMT reliability concerns and the board area impact of MIL SPEC SMT components is addressed. Package selection for the analog ASIC is discussed. Future sytems will require even denser packaging and the volume reduction progression is shown.

Chemopreventive role of green tea in head and neck cancers.

PubMed

Kim, Yoo Suk; Kim, Chul-Ho

2014-03-01

In the era of personalized medicine, selecting the ideal treatment modality for head and neck cancer is becoming more complex. Also, despite the use of the newest agents, overall survival has not been improved notably over the past few decades. Currently, in accordance with the development of diagnostic tools, prevention and early detection of cancer are being emphasized more in obtaining better treatment outcomes. Among the various cancer preventative methods, the use of green tea is one of the most common approaches, and tea is known to be involved in multiple steps of carcinogenesis. Thus, in this short review, the protective roles of green tea components against the initiation, progression, and metastasis of head and neck malignancies will be discussed.

Discrimination techniques employing both reflective and thermal multispectral signals. [for remote sensor technology

NASA Technical Reports Server (NTRS)

Malila, W. A.; Crane, R. B.; Richardson, W.

1973-01-01

Recent improvements in remote sensor technology carry implications for data processing. Multispectral line scanners now exist that can collect data simultaneously and in registration in multiple channels at both reflective and thermal (emissive) wavelengths. Progress in dealing with two resultant recognition processing problems is discussed: (1) More channels mean higher processing costs; to combat these costs, a new and faster procedure for selecting subsets of channels has been developed. (2) Differences between thermal and reflective characteristics influence recognition processing; to illustrate the magnitude of these differences, some explanatory calculations are presented. Also introduced, is a different way to process multispectral scanner data, namely, radiation balance mapping and related procedures. Techniques and potentials are discussed and examples presented.

NASA's aircraft icing technology program

NASA Technical Reports Server (NTRS)

Reinmann, John J.

1991-01-01

NASA' Aircraft Icing Technology program is aimed at developing innovative technologies for safe and efficient flight into forecasted icing. The program addresses the needs of all aircraft classes and supports both commercial and military applications. The program is guided by three key strategic objectives: (1) numerically simulate an aircraft's response to an in-flight icing encounter, (2) provide improved experimental icing simulation facilities and testing techniques, and (3) offer innovative approaches to ice protection. Our research focuses on topics that directly support stated industry needs, and we work closely with industry to assure a rapid and smooth transfer of technology. This paper presents selected results that illustrate progress towards the three strategic objectives, and it provides a comprehensive list of references on the NASA icing program.

Automation literature: A brief review and analysis

NASA Technical Reports Server (NTRS)

Smith, D.; Dieterly, D. L.

1980-01-01

Current thought and research positions which may allow for an improved capability to understand the impact of introducing automation to an existing system are established. The orientation was toward the type of studies which may provide some general insight into automation; specifically, the impact of automation in human performance and the resulting system performance. While an extensive number of articles were reviewed, only those that addressed the issue of automation and human performance were selected to be discussed. The literature is organized along two dimensions: time, Pre-1970, Post-1970; and type of approach, Engineering or Behavioral Science. The conclusions reached are not definitive, but do provide the initial stepping stones in an attempt to begin to bridge the concept of automation in a systematic progression.