Sample records for visiting cms experimental

  1. 42 CFR 401.719 - Monitoring and sanctioning of qualified entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Data for Performance Measurement § 401.719 Monitoring and sanctioning of qualified entities. (a) CMS... methods: (1) Audits. (2) Submission of documentation of data sources and quantities of data upon the request of CMS and/or site visits. (3) Analysis of specific data reported to CMS by qualified entities...

  2. Repeatability of Central and Peripheral Pulse Wave Velocity Measures: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Tanaka, Hirofumi; Palta, Priya; Patel, Mehul D.; Camplain, Ricky; Couper, David; Cheng, Susan; Al Qunaibet, Ada; Poon, Anna K.; Heiss, Gerardo

    2016-01-01

    BACKGROUND Arterial stiffness measures are emerging tools for risk assessment and stratification for hypertension and cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (cfPWV) is an established measure of central arterial stiffness. Other measures of PWV include femoral-ankle (faPWV), a measure of peripheral stiffness, and brachial-ankle PWV (baPWV), a composite measure of central and peripheral stiffness. Repeatability of central, peripheral, and composite PWV measures has not been adequately examined or compared. METHODS Participants (n = 79; mean age 75.7 years; USA) from a repeatability study nested within the Atherosclerosis Risk in Communities (ARIC) Study visit 5 (2011–2013) underwent 2 standardized visits, 4–8 weeks apart. Trained technicians obtained 2 PWV measurements at each visit using the VP-1000 Plus system. We calculated the intraclass correlation coefficient (ICC), SE of measurement, and minimal detectable change (MDC95; 95% confidence interval) and difference (MDD). RESULTS The ICCs and 95% confidence intervals (95% CIs) were 0.70 (0.59, 0.81) for cfPWV, 0.84 (0.78, 0.90) for baPWV, and 0.69 (0.59, 0.79) for faPWV. The MDC95 between repeat measures within an individual was 411.0cm/s for cfPWV, 370.6cm/s for baPWV, and 301.4cm/s for faPWV. The MDD for 2 independent samples of 100 per group was 139.3cm/s for cfPWV, 172.3cm/s for baPWV, and 100.4cm/s for faPWV. CONCLUSIONS Repeatability was acceptable for all PWV measures in a multicenter, population-based study of older adults and supports its use in epidemiologic studies. Quantifying PWV measurement variation is critical for applications to risk assessment and stratification and eventual translation to clinical practice. PMID:26232036

  3. Promoting Prenatal Health and Positive Birth Outcomes: A Snapshot of State Efforts. OPRE Report 2017-65

    ERIC Educational Resources Information Center

    Sparr, Mariel; Joraanstad, Alexandra; Atukpawu-Tipton, Grace; Miller, Nicole; Leis, Julie; Filene, Jill

    2017-01-01

    To promote prenatal health and improve birth outcomes, the Centers for Medicare and Medicaid Services (CMS) developed the Strong Start for Mothers and Newborns initiative. The Strong Start initiative is assessing several enhanced prenatal care approaches, including home visiting. As part of the Strong Start initiative, CMS, in partnership with the…

  4. Initial home health outcomes under prospective payment.

    PubMed

    Schlenker, Robert E; Powell, Martha C; Goodrich, Glenn K

    2005-02-01

    To assess initial changes in home health patient outcomes under Medicare's home health Prospective Payment System (PPS), implemented by the Centers for Medicare and Medicaid Services (CMS) in October 2000. Pre-PPS and early PPS data were obtained from CMS Outcome and Assessment Information Set (OASIS) and Medicare claims files. Regression analysis was applied to national random samples (n=164,810) to estimate pre-PPS/PPS outcome and visit-per-episode changes. Outcome episodes were constructed from OASIS data and linked with Medicare claims data on visits. Outcome changes (risk adjusted) were mixed and generally modest. Favorable changes included higher improvement rates under PPS for functioning and dyspnea, higher community discharge rates, and lower hospitalization and emergent care rates. Most stabilization (nonworsening) outcome rates also increased. However, improvement rates were lower under PPS for wounds, incontinence, and cognitive and emotional/behavioral outcomes. Total visits per episode (case-mix adjusted) declined 16.6 percent although therapy visits increased by 8.4 percent. The outcome and visit results suggest improved system efficiency under PPS (fewer visits, similar outcomes). However, declines in several improvement rates merit ongoing monitoring, as do subsequent (posthome health) hospitalization and emergent care use. Since only the early PPS period was examined, longer-term analyses are needed.

  5. The Importance of Mid-to-Late-Life Body Mass Index Trajectories on Late-Life Gait Speed.

    PubMed

    Windham, B Gwen; Griswold, Michael E; Wang, Wanmei; Kucharska-Newton, Anna; Demerath, Ellen W; Gabriel, Kelley Pettee; Pompeii, Lisa A; Butler, Kenneth; Wagenknecht, Lynne; Kritchevsky, Stephen; Mosley, Thomas H

    2017-08-01

    Prior studies suggest being overweight may be protective against poor functional outcomes in older adults. Body mass index (BMI, kg/m2) was measured over 25 years across five visits (1987-2011) among Atherosclerosis Risk in Communities Study participants (baseline Visit 1 n = 15,720, aged 45-64 years). Gait speed was measured at Visit 5 ("late-life", aged ≥65 years, n = 6,229). BMI trajectories were examined using clinical cutpoints and continuous mixed models to estimate effects of patterns of BMI change on gait speed, adjusting for demographics and comorbidities. Mid-life BMI (baseline visit; 55% women; 27% black) was associated with late-life gait speed 25 years later; gait speeds were 94.3, 89.6, and 82.1 cm/s for participants with baseline normal BMI (<25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30) (p < .001). In longitudinal analyses, late-life gait speeds were 96.9, 88.8, and 81.3 cm/s for participants who maintained normal, overweight, and obese weight status, respectively, across 25 years (p < .01). Increasing BMI over 25 years was associated with poorer late-life gait speeds; a 1%/year BMI increase for a participant with a baseline BMI of 22.5 (final BMI 28.5) was associated with a 4.6-cm/s (95% confidence interval: -7.0, -1.8) slower late-life gait speed than a participant who maintained a baseline BMI of 22.5. Being overweight in older age was not protective of mobility function. Maintaining a normal BMI in mid- and late-life may help preserve late-life mobility. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. [Research survey on the information gathering methods, attitudes, and requests from care managers about the pharmaceutical service by pharmacists in home care].

    PubMed

    Nanaumi, Yoko; Onda, Mitsuko; Sakurai, Hidehiko; Tanaka, Rie; Tsubota, Kenichi; Matoba, Shunya; Mukai, Yusuke; Arakawa, Yukio; Hayase, Yukitoshi

    2011-01-01

    Care Managers (CMs) were surveyed to clarify the issues involving the promotion of cooperation between care managers and pharmacists in long-term-care and explore solutions. The length of work experience, occupational background, experience of pharmaceutical service; pharmacist visit patients' home for providing medicine and pharmaceutical care into a care plan, degree of understanding on pharmaceutical service, and awareness of work involved in pharmaceutical service were studied to see whether there made differences in the requests from CMs for information on pharmacists and for information gathering methods. The χ(2) test was used to this end. The opinions and requests described by the CMs were validated through text mining. More CMs tended to obtain information and knowledge through training sessions and professional magazines than those who did so through cooperation with pharmacists on a practical level. However, the survey strongly indicated that CMs with high level of understanding and awareness of pharmaceutical service wished to obtain information on pharmacists through cooperation with them on a practical level, and CMs with low level of understanding and awareness of pharmaceutical service wished to obtain such information through training sessions and professional magazines. Results of text mining showed that CMs wished pharmacists to strengthen the cooperation with physicians and provide information on pharmaceutical service. These findings have led to the conclusion that the issues surrounding the promotion of cooperation between CMs and pharmacists centered around "work cooperation on a practical level" and "provision of information to CMs about the roles of pharmacies and pharmacists and their work."

  7. A novel totivirus and piscine reovirus (PRV) in Atlantic salmon (Salmo salar) with cardiomyopathy syndrome (CMS).

    PubMed

    Løvoll, Marie; Wiik-Nielsen, Jannicke; Grove, Søren; Wiik-Nielsen, Christer R; Kristoffersen, Anja B; Faller, Randi; Poppe, Trygve; Jung, Joonil; Pedamallu, Chandra S; Nederbragt, Alexander J; Meyerson, Matthew; Rimstad, Espen; Tengs, Torstein

    2010-11-10

    Cardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS. Using high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS a high number of sequence reads identical to the PRV genome were identified. In addition, a sequence contig from a novel totivirus could also be constructed. Using RT-qPCR, levels of PRV in tissue samples were quantified and the totivirus was detected in all samples tested from CMS fish but not in controls. In situ hybridization supported this pattern indicating a possible association between CMS and the novel piscine totivirus. Although causality for CMS in Atlantic salmon could not be proven for either of the two viruses, our results are compatible with a hypothesis where, in the experimental challenge studied, PRV behaves as an opportunist whereas the totivirus might be more directly linked with the development of CMS.

  8. Medicare Coverage Strategies: Impact of the MMA and PBMs

    PubMed Central

    Antos, Joseph

    2008-01-01

    American Health & Drug Benefits ™ has been created to act as an ideological melting pot focusing on health and drug benefit decision makers, as well as those who may affect or may be affected by those decisions. By engaging in conversations with payors, regulators, employers, and other stakeholders, our journal hopes to enable decision makers to view the impact of benefit designs from as many perspectives as possible. Through this open dialogue, we hope that better decisions may be made, and that the greater healthcare marketplace will be positively impacted. In following our editorial mission, American Health & Drug Benefits ™ has sought thought leaders who have influenced and will continue to influence the healthcare marketplace. During a fall visit to Washington, DC, Dr. Joseph Antos was kind enough to host a visit to the American Enterprise Institute and provide his thoughts to Robert Henry, editor-in-chief, on how the Centers for Medicare & Medicaid Services (CMS) exerts its influence on drug coverage in the wake of the Medicare Modernization Act (MMA) and in the face of evidence-based medicine standards. Following a chronology of CMS's role from its inception to current events, Dr. Antos offers a lively insight into CMS's strategy and its tactical effects on the American healthcare system. PMID:25126207

  9. Value-based contracting innovated Medicare advantage healthcare delivery and improved survival.

    PubMed

    Mandal, Aloke K; Tagomori, Gene K; Felix, Randell V; Howell, Scott C

    2017-02-01

    In Medicare Advantage (MA) with its CMS Hierarchical Condition Categories (CMS-HCC) payment model, CMS reimburses private plans (Medicare Advantage Organizations [MAOs]) with prospective, monthly, health-based or risk-adjusted, capitated payments. The effect of this payment methodology on healthcare delivery remains debatable. How value-based contracting generates cost efficiencies and improves clinical outcomes in MA is studied. A difference in contracting arrangements between an MAO and 2 provider groups facilitated an intervention-control, preintervention-postintervention, difference-in-differences approach among statistically similar, elderly, community-dwelling MA enrollees within one metropolitan statistical area. Starting in 2009, for intervention-group MA enrollees, the MAO and a provider group agreed to full-risk capitation combined with a revenue gainshare. The gainshare was based on increases in the Risk Adjustment Factor (RAF), which modified the CMS-HCC payments. For the control group, the MAO continued to reimburse another provider group through fee-for-service. RAF, utilization, and survival were followed until December 31, 2012. The intervention group's mean RAF increased significantly (P <.001), estimating $2,519,544 per 1000 members of additional revenue. The intervention increased office-based visits (P <.001). Emergency department visits (P <.001) and inpatient hospital admissions (P = .002) decreased. This change in utilization saved $2,071,293 per 1000 enrollees. By intensifying office-based care for these MA enrollees with multiple comorbidities, a 6% survival benefit with a 32.8% lower hazard of death (P <.001) was achieved. Value-based contracting can drive utilization patterns and improve clinical outcomes among chronically ill, elderly MA members.

  10. 'The right direction'. Primary-care docs see promise in CMS' proposed pay for non face-to-face work.

    PubMed

    Robeznieks, Andis

    2013-07-15

    The CMS has proposed paying physicians for managing patients apart from face-to-face office visits. Among the details under consideration are requiring practices to use an electronic health-record system that supports access to care, care coordination, care management and communications. "It's a step in the right direction. The devil will be in the details and, if the burden of documentation is so high, people may choose not to spend their time doing it," says Dr. Matt Handley, physician and medical director for quality at the Group Health Cooperative.

  11. 42 CFR § 512.605 - Waiver of certain telehealth requirements.

    Code of Federal Regulations, 2010 CFR

    2017-10-01

    ... AND HUMAN SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL... distant site payment for telehealth home visit HCPCS codes unique to this model to more accurately reflect... accordance with § 512.210. (c) Waiver of selected payment provisions. (1) CMS waives the payment requirements...

  12. Applying the Technology Acceptance Model (TAM) to Explore the Effects of a Course Management System (CMS)-Assisted EFL Writing Instruction

    ERIC Educational Resources Information Center

    Tsai, Yea-Ru

    2015-01-01

    This study illustrates a teaching model that utilizes a Blackboard (Bb) course management system (CMS) to support English writing instruction. It was implemented in a blended English research paper (RP) writing course, with specific learning resources and activities offered inside and outside the Bb CMS. A quasi-experimental study in which the…

  13. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

    2013-10-01

    Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

  14. Automatic identification of bullet signatures based on consecutive matching striae (CMS) criteria.

    PubMed

    Chu, Wei; Thompson, Robert M; Song, John; Vorburger, Theodore V

    2013-09-10

    The consecutive matching striae (CMS) numeric criteria for firearm and toolmark identifications have been widely accepted by forensic examiners, although there have been questions concerning its observer subjectivity and limited statistical support. In this paper, based on signal processing and extraction, a model for the automatic and objective counting of CMS is proposed. The position and shape information of the striae on the bullet land is represented by a feature profile, which is used for determining the CMS number automatically. Rapid counting of CMS number provides a basis for ballistics correlations with large databases and further statistical and probability analysis. Experimental results in this report using bullets fired from ten consecutively manufactured barrels support this developed model. Published by Elsevier Ireland Ltd.

  15. A Whole-Body Physiologically Based Pharmacokinetic Model for Colistin and Colistin methanesulfonate (CMS) in Rat.

    PubMed

    Bouchene, Salim; Marchand, Sandrine; Couet, William; Friberg, Lena E; Gobin, Patrice; Lamarche, Isabelle; Grégoire, Nicolas; Björkman, Sven; Karlsson, Mats O

    2018-04-17

    Colistin is a polymyxin antibiotic used to treat patients infected with multidrug-resistant Gram negative bacteria (MDR-GNB). The objective of this work was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model to predict tissue distribution of colistin in rat. The distribution of a drug in a tissue is commonly characterized by its tissue-to-plasma partition coefficient, K p . Colistin and its prodrug, colistin methanesulfonate (CMS) K p priors were measured experimentally from rat tissue homogenates or predicted in silico. The PK parameters of both compounds were estimated fitting in vivo their plasma concentration-time profiles from six rats receiving an i.v. bolus of CMS. The variability in the data was quantified by applying a non-linear mixed effect (NLME) modelling approach. A WB-PBPK model was developed assuming a well-stirred and perfusion-limited distribution in tissue compartments. Prior information on tissue distribution of colistin and CMS was investigated following three scenarios: K p were estimated using in silico K p priors (I) or K p were estimated using experimental K p priors (II) or K p were fixed to the experimental values (III). The WB-PBPK model best described colistun and CMS plasma concentration-time profiles in scenario II. Colistin predicted concentrations in kidneys in scenario II were higher than in other tissues, which was consistent with its large experimental K p prior. This might be explained by a high affinity of colistin for renal parenchyma and active reabsorption into the proximal tubular cells. In contrast, renal accumulation of colistin was not predicted in scenario I. Colistin and CMS clearance estimates were in agreement with published values. The developed model suggests using experimental priors over in silico K p priors for kidneys to provide a better prediction of colistin renal distribution. Such models might serve in drug development for interspecies scaling and investigating the impact of disease state on colistin disposition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. 42 CFR 484.215 - Initial establishment of the calculation of the national 60-day episode payment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... costs for the period. CMS determines the national mean cost per visit. (b) Determining HHA utilization... mean utilization for each of the six disciplines using home health claims data. (c) Use of the market... computing the national mean utilization for each discipline. (3) By multiplying the mean national cost per...

  17. Seema Verma Does Her Homework, Pushes for Beneficiaries To Have More Skin in the Game.

    PubMed

    Kelley, Timothy

    2017-08-01

    The new head of CMS recently wrote the nation's governors urging that Medicaid recipients be required to pay premiums, be charged for ER visits, and be encouraged to get jobs or job training. This "skin in the game" approach appeals to conservatives, though critics say it can depress participation among the poor.

  18. Prudentia: A Medical School's Solution to Curriculum Mapping and Curriculum Management

    ERIC Educational Resources Information Center

    Steketee, Carole

    2015-01-01

    During early accreditation visits by the Australian Medical Council (AMC), staff in the School of Medicine (SoM) were asked to demonstrate how and when AMC student outcome statements were being integrated into the MBBS course. As a result, the School Executive committed to developing a curriculum mapping system (CMS) that could systematically…

  19. Physics with CMS and Electronic Upgrades

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

    Rohlf, James W.

    2016-08-01

    The current funding is for continued work on the Compact Muon Solenoid (CMS) at the CERN Large Hadron Collider (LHC) as part of the Energy Frontier experimental program. The current budget year covers the first year of physics running at 13 TeV (Run 2). During this period we have concentrated on commisioning of the μTCA electronics, a new standard for distribution of CMS trigger and timing control signals and high bandwidth data aquistiion as well as participating in Run 2 physics.

  20. Medicare's "Global" terrorism: where is the pay for performance?

    PubMed

    Reed, R Lawrence; Luchette, Fred A; Esposito, Thomas J; Pyrz, Karen; Gamelli, Richard L

    2008-02-01

    Medicare and Medicaid Services (CMS) payment policies for surgical operations are based on a global package concept. CMS' physician fee schedule splits the global package into preoperative, intraoperative, and postoperative components of each procedure. We hypothesized that these global package component valuations were often lower than comparable evaluation and management (E&M) services and that billing for E&M services instead of the operation could often be more profitable. Our billing database and Trauma Registry were queried for the operative procedures and hospital lengths of stay for trauma patients during the past 5 years. Determinations of preoperative, intraoperative, and postoperative payments were calculated for 10-day and 90-day global packages, comparing them to CMS payments for comparable E&M codes. Of 90-day and 10-day Current Procedural Terminology codes, 88% and 100%, respectively, do not pay for the comprehensive history and physical that trauma patients usually receive, whereas 41% and 98%, respectively, do not even meet payment levels for a simple history and physical. Of 90-day global package procedures, 70% would have generated more revenue had comprehensive daily visits been billed instead of the operation ($3,057,500 vs. $1,658,058). For 10-day global package procedures, 56% would have generated more revenue with merely problem-focused daily visits instead of the operation ($161,855 vs. $156,318). Medicare's global surgical package underpays E&M services in trauma patients. In most cases, trauma surgeons would fare better by not billing for operations to receive higher reimbursement for E&M services that are considered "bundled" in the global package payment.

  1. Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain.

    PubMed

    Nazıroğlu, Mustafa; Kozlu, Süleyman; Yorgancıgil, Emre; Uğuz, Abdülhadi Cihangir; Karakuş, Kadir

    2013-01-01

    Oxidative stress is a critical route of damage in various physiological stress-induced disorders, including depression. Rose oil may be a useful treatment for depression because it contains flavonoids which include free radical antioxidant compounds such as rutin and quercetin. We investigated the effects of absolute rose oil (from Rosa × damascena Mill.) and experimental depression on lipid peroxidation and antioxidant levels in the cerebral cortex of rats. Thirty-two male rats were randomly divided into four groups. The first group was used as control, while depression was induced in the second group using chronic mild stress (CMS). Oral (1.5 ml/kg) and vapor (0.15 ml/kg) rose oil were given for 28 days to CMS depression-induced rats, constituting the third and fourth groups, respectively. The sucrose preference test was used weekly to identify depression-like phenotypes during the experiment. At the end of the experiment, cerebral cortex samples were taken from all groups. The lipid peroxidation levels in the cerebral cortex in the CMS group were higher than in control whereas their levels were decreased by rose oil vapor exposure. The vitamin A, vitamin E, vitamin C and β-carotene concentrations in the cerebral cortex were lower in the CMS group than in the control group whereas their concentrations were higher in the rose oil vapor plus CMS group. The CMS-induced antioxidant vitamin changes were not modulated by oral treatment. Glutathione peroxidase activity and reduced glutathione did not change statistically in the four groups following CMS or either treatment. In conclusion, experimental depression is associated with elevated oxidative stress while treatment with rose oil vapor induced protective effects on oxidative stress in depression.

  2. Self-referral of imaging and increased utilization: some practical perspectives on tackling the dilemma.

    PubMed

    Romano, Donald H

    2009-11-01

    Health care costs are higher in the United States than in any other country in the world, and imaging services have been growing much more rapidly than other services. Studies have shown a tendency for increased utilization of services, including imaging services, when referring physicians have ownership interest in the services. In recent years, the CMS has taken some action with respect to how it pays for imaging, including reducing physician payments when multiple images are taken on contiguous body parts during the same visit, establishing a cap on payments for certain imaging services, and imposing an antimarkup rule on diagnostic tests. In addition, CMS has made some changes to the Stark rules, which included adding nuclear medicine to the list of designated health services, prohibiting certain per-service or per-click leasing arrangements, and prohibiting physicians from owning entities that sell services to providers that then bill for them under arrangements. Because it is unclear whether these policy changes will have much effect on imaging utilization, CMS will continue to seek new ways to rein in utilization. In the near future, CMS and the US Department of Health and Human Services are likely to attempt to curb utilization not only through postpayment review and education but also through its various initiatives on improving the quality of services furnished to Medicare benificiaries.

  3. Choice of Tuning Parameters on 3D IC Engine Simulations Using G-Equation

    DOE PAGES

    Liu, Jinlong; Szybist, James; Dumitrescu, Cosmin

    2018-04-03

    3D CFD spark-ignition IC engine simulations are extremely complex for the regular user. Truly-predictive CFD simulations for the turbulent flame combustion that solve fully coupled transport/chemistry equations may require large computational capabilities unavailable to regular CFD users. A solution is to use a simpler phenomenological model such as the G-equation that decouples transport/chemistry result. Such simulation can still provide acceptable and faster results at the expense of predictive capabilities. While the G-equation is well understood within the experienced modeling community, the goal of this paper is to document some of them for a novice or less experienced CFD user whomore » may not be aware that phenomenological models of turbulent flame combustion usually require heavy tuning and calibration from the user to mimic experimental observations. This study used ANSYS® Forte, Version 17.2, and the built-in G-equation model, to investigate two tuning constants that influence flame propagation in 3D CFD SI engine simulations: the stretch factor coefficient, Cms and the flame development coefficient, Cm2. After identifying several Cm2-Cms pairs that matched experimental data at one operating conditions, simulation results showed that engine models that used different Cm2-Cms sets predicted similar combustion performance, when the spark timing, engine load, and engine speed were changed from the operating condition used to validate the CFD simulation. A dramatic shift was observed when engine speed was doubled, which suggested that the flame stretch coefficient, Cms, had a much larger influence at higher engine speeds compared to the flame development coefficient, Cm2. Therefore, the Cm2-Cms sets that predicted a higher turbulent flame under higher in-cylinder pressure and temperature increased the peak pressure and efficiency. This suggest that the choice of the Cm2-Cms will affect the G-equation-based simulation accuracy when engine speed increases from the one used to validate the model. As a result, for the less-experienced CFD user and in the absence of enough experimental data that would help retune the tuning parameters at various operating conditions, the purpose of a good G-equation-based 3D engine simulation is to guide and/or complement experimental investigations, not the other way around. Only a truly-predictive simulation that fully couples the turbulence/chemistry equations can help reduce the amount of experimental work.« less

  4. Choice of Tuning Parameters on 3D IC Engine Simulations Using G-Equation

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

    Liu, Jinlong; Szybist, James; Dumitrescu, Cosmin

    3D CFD spark-ignition IC engine simulations are extremely complex for the regular user. Truly-predictive CFD simulations for the turbulent flame combustion that solve fully coupled transport/chemistry equations may require large computational capabilities unavailable to regular CFD users. A solution is to use a simpler phenomenological model such as the G-equation that decouples transport/chemistry result. Such simulation can still provide acceptable and faster results at the expense of predictive capabilities. While the G-equation is well understood within the experienced modeling community, the goal of this paper is to document some of them for a novice or less experienced CFD user whomore » may not be aware that phenomenological models of turbulent flame combustion usually require heavy tuning and calibration from the user to mimic experimental observations. This study used ANSYS® Forte, Version 17.2, and the built-in G-equation model, to investigate two tuning constants that influence flame propagation in 3D CFD SI engine simulations: the stretch factor coefficient, Cms and the flame development coefficient, Cm2. After identifying several Cm2-Cms pairs that matched experimental data at one operating conditions, simulation results showed that engine models that used different Cm2-Cms sets predicted similar combustion performance, when the spark timing, engine load, and engine speed were changed from the operating condition used to validate the CFD simulation. A dramatic shift was observed when engine speed was doubled, which suggested that the flame stretch coefficient, Cms, had a much larger influence at higher engine speeds compared to the flame development coefficient, Cm2. Therefore, the Cm2-Cms sets that predicted a higher turbulent flame under higher in-cylinder pressure and temperature increased the peak pressure and efficiency. This suggest that the choice of the Cm2-Cms will affect the G-equation-based simulation accuracy when engine speed increases from the one used to validate the model. As a result, for the less-experienced CFD user and in the absence of enough experimental data that would help retune the tuning parameters at various operating conditions, the purpose of a good G-equation-based 3D engine simulation is to guide and/or complement experimental investigations, not the other way around. Only a truly-predictive simulation that fully couples the turbulence/chemistry equations can help reduce the amount of experimental work.« less

  5. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    PubMed

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  6. Touch Satiety: Differential Effects of Stroking Velocity on Liking and Wanting Touch Over Repetitions

    PubMed Central

    Triscoli, Chantal; Ackerley, Rochelle; Sailer, Uta

    2014-01-01

    A slow, gentle caress of the skin is a salient hedonic stimulus. Low threshold, unmyelinated C-tactile afferents fire preferentially to this type of touch, where slow (<1 cm/s) and fast (>10 cm/s) stroking velocities produce lower firing frequencies and are rated as less pleasant. The current aim was to investigate how the experience of tactile pleasantness changes with repeated exposure (satiety to touch). A further aim was to determine whether tactile satiety varied with different stroking velocities. The experimental paradigm used a controlled brush stroke to the forearm that was delivered repeatedly for ∼50 minutes. In Experiment 1, brush strokes were administered at three different velocities (0.3 cm/s, 3 cm/s and 30 cm/s), which were presented in a pseudo-randomised order. In Experiment 2, brush strokes were applied using only one velocity (either 3 or 30 cm/s). After each stroke, the participants rated both subjective pleasantness (liking) and wanting (the wish to be further exposed to the same stimulus) for each tactile sensation. In Experiment 1, both pleasantness and wanting showed a small, but significant, decrease over repetitions during stroking at 3 cm/s only, where the mean values for pleasantness and wanting were similar. Conversely, slower (0.3 cm/s) and faster (30 cm/s) stroking showed no decrease in ratings over time, however pleasantness was rated higher than wanting. In Experiment 2, both pleasantness and wanting showed a significant decrease over repetitions for both applied velocities, with a larger decrease in ratings for stroking at 3 cm/s. In conclusion, satiety to touch occurred with a slow onset and progression, where pleasantness and wanting ratings to stroking at 3 cm/s were affected more than at the slower or faster velocities. Tactile satiety appears to differ compared to appetitive and olfactory satiety, because the hedonic and rewarding aspects of touch persist for some time. PMID:25405620

  7. Comparative meta-analysis and experimental kinetic investigation of column and batch bottle microcosm treatability studies informing in situ groundwater remedial design.

    PubMed

    Driver, Erin M; Roberts, Jeff; Dollar, Peter; Charles, Maurissa; Hurst, Paul; Halden, Rolf U

    2017-02-05

    A systematic comparison was performed between batch bottle and continuous-flow column microcosms (BMs and CMs, respectively) commonly used for in situ groundwater remedial design. Review of recent literature (2000-2014) showed a preference for reporting batch kinetics, even when corresponding column data were available. Additionally, CMs produced higher observed rate constants, exceeding those of BMs by a factor of 6.1±1.1 standard error. In a subsequent laboratory investigation, 12 equivalent microcosm pairs were constructed from fractured bedrock and perchloroethylene (PCE) impacted groundwater. First-order PCE transformation kinetics of CMs were 8.0±4.8 times faster than BMs (rates: 1.23±0.87 vs. 0.16±0.05d -1 , respectively). Additionally, CMs transformed 16.1±8.0-times more mass than BMs owing to continuous-feed operation. CMs are concluded to yield more reliable kinetic estimates because of much higher data density stemming from long-term, steady-state conditions. Since information from BMs and CMs is valuable and complementary, treatability studies should report kinetic data from both when available. This first systematic investigation of BMs and CMs highlights the need for a more unified framework for data use and reporting in treatability studies informing decision-making for field-scale groundwater remediation. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Beam-dynamic effects at the CMS BRIL van der Meer scans

    NASA Astrophysics Data System (ADS)

    Babaev, A.

    2018-03-01

    The CMS Beam Radiation Instrumentation and Luminosity Project (BRIL) is responsible for the simulation and measurement of luminosity, beam conditions and radiation fields in the CMS experiment. The project is engaged in operating and developing new detectors (luminometers), adequate for the experimental conditions associated with high values of instantaneous luminosity delivered by the CERN LHC . BRIL operates several detectors based on different physical principles and technologies. Precise and accurate measurements of the delivered luminosity is of paramount importance for the CMS physics program. The absolute calibration of luminosity is achieved by the van der Meer method, which is carried out under specially tailored conditions. This paper presents models used to simulate of beam-dynamic effects arising due to the electromagnetic interaction of colliding bunches. These effects include beam-beam deflection and dynamic-β effect. Both effects are important to luminosity measurements and influence calibration constants at the level of 1-2%. The simulations are carried out based on 2016 CMS van der Meer scan data for proton-proton collisions at a center-of-mass energy of 13 TeV.

  9. Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells.

    PubMed

    Chen, Ying-Jung; Wang, Jeh-Jeng; Chang, Long-Sen

    2011-11-01

    1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

  10. Tailoring Mathematical Models to Stem-Cell Derived Cardiomyocyte Lines Can Improve Predictions of Drug-Induced Changes to Their Electrophysiology.

    PubMed

    Lei, Chon Lok; Wang, Ken; Clerx, Michael; Johnstone, Ross H; Hortigon-Vinagre, Maria P; Zamora, Victor; Allan, Andrew; Smith, Godfrey L; Gavaghan, David J; Mirams, Gary R; Polonchuk, Liudmila

    2017-01-01

    Human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have applications in disease modeling, cell therapy, drug screening and personalized medicine. Computational models can be used to interpret experimental findings in iPSC-CMs, provide mechanistic insights, and translate these findings to adult cardiomyocyte (CM) electrophysiology. However, different cell lines display different expression of ion channels, pumps and receptors, and show differences in electrophysiology. In this exploratory study, we use a mathematical model based on iPSC-CMs from Cellular Dynamic International (CDI, iCell), and compare its predictions to novel experimental recordings made with the Axiogenesis Cor.4U line. We show that tailoring this model to the specific cell line, even using limited data and a relatively simple approach, leads to improved predictions of baseline behavior and response to drugs. This demonstrates the need and the feasibility to tailor models to individual cell lines, although a more refined approach will be needed to characterize individual currents, address differences in ion current kinetics, and further improve these results.

  11. Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

    PubMed

    Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

    2012-08-01

    The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Experimental Verification of Material Flammability in Space

    NASA Technical Reports Server (NTRS)

    Ivanov, A. V.; Balashov, Y. V.; Andreeva, T. V.; Melikhov, A. S.

    1999-01-01

    The flammability in microgravity of three US-furnished materials, Delrin, polymethylmethacrylate (PMMA), and high-density polyethylene, was determined using a Russian-developed combustion tunnel on Mir. Four 4.5-mm-diameter cylindrical samples of each plastic were ignited under concurrent airflow (in the direction of flame spread) with velocities from no flow to 8.5 cm/s. The test results identify a limiting air-flow velocity V(sub lim) for each material, below which combustion ceases. Nominal values are V(sub lim) < 0.3 cm/s for Delrin, 0.5 cm/s for PMMA, and 0.3 to 0.5 cm/s for polyethylene. These values are lower than those obtained in prior ground testing. Nevertheless, they demonstrate that flow shutoff is effective for extinguishment in the microgravity environment of spacecraft. Microgravity test results also show that the plastic materials maintain a stable melt ball within the spreading flame zone. In general, as the concurrent flow velocity V decreases, the flame-spread rate V(sub F) decreases, from an average (for all three materials) of V(sub F)= 0.5-0.75 mm/s at V = 8.5 cm/s to V(sub F)= 0.05-0.01 mm/s at V = 0.3-0.5 cm/s. Also, as V decreases, the flames become less visible but expand, increasing the probability of igniting an adjacent surface.

  13. Impact of calcium-sensitive dyes on the beating properties and pharmacological responses of human iPS-derived cardiomyocytes using the calcium transient assay.

    PubMed

    Kopljar, Ivan; Hermans, An N; Teisman, Ard; Gallacher, David J; Lu, Hua Rong

    Calcium-based screening of hiPS-CMs is a useful preclinical safety evaluation platform with the ability to generate robust signals that facilitates high-throughput screening and data analysis. However, due to the potential inherent toxicities, it is important to understand potential effects of different calcium-sensitive dyes on the hiPS-CMs model. We compared three calcium-sensitive fluorescence dyes (Cal520, ACTOne and Calcium 5) for their impact on the variability, the beating properties and the pharmacological responses of hiPS-CMs using the Hamamatsu FDSS/μCell imaging platform. Direct effects of three dyes on the electrophysiological properties of hiPS-CMs were evaluated with the multi-electrode array (MEA) Axion Maestro platform. We propose a specific experimental protocol for each dye which gives the most optimal assay conditions to minimize variability and possible adverse effects. We showed that Cal520 had the smallest effect on hiPS-CMs together with the longest-lasting stable amplitude signal (up to 4 h). Although all dyes had a (minor) acute effect on hiPS-CMs, in the form of reduced beat rate and prolonged field potential duration, the selection of the dye did not influence the pharmacological response of four cardioactive drugs (dofetilide, moxifloxacin, nimodipine and isoprenaline). In conclusion, we have documented that different calcium sensitive dyes have only minor direct (acute) effects on hiPS-CMs with Cal520 showing the least effects and the longest lasting signal amplitude. Importantly, drug-induced pharmacological responses in hiPS-CMs were comparable between the three dyes. These findings should help further improve the robustness of the hiPS-CMs-based calcium transient assay as a predictive, preclinical cardiac safety evaluation tool. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Thermal diffusivity of alpha-mercuric iodide

    NASA Astrophysics Data System (ADS)

    Burger, A.; Morgan, S. H.; Henderson, D. O.; Silberman, E.; Nason, D.

    1991-01-01

    The thermal diffusivity and its anisotropy is measured along the principal axes of tetragonal alpha-HgI2 semiconductor single crystals grown from vapor. The experiments are carried out using the flash pulse method. The results show that alpha(100-line-type) = 0.00370 sq cm/s + or - 3 percent and alpha(001-line-type = 0.00103 sq cm/s + or - 10 percent. Necessary corrections are made for the experimental variables of heat losses and finite pulse duration in the data analysis.

  15. Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

    PubMed Central

    Iorga, Bogdan; Schwanke, Kristin; Weber, Natalie; Wendland, Meike; Greten, Stephan; Piep, Birgit; dos Remedios, Cristobal G.; Martin, Ulrich; Zweigerdt, Robert; Kraft, Theresia; Brenner, Bernhard

    2018-01-01

    Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC) isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs) differentiated in vitro resemble those of human ventricular myofibrils (hvMFs) isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs) and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1), reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa) than for hvMFs (94 kPa). At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04) than for hvMFs (pCa50 = 5.80). At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1) than for hvMFs (0.28 s−1). During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1) than for hvMFs (0.21 s−1), while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins, explaining the functional discrepancies. The sarcomeric protein isoform pattern of hESC-CMs had features of human cardiomyocytes at an early developmental stage. The study indicates that morphological and ultrastructural maturation of βMyHC isoform-expressing hESC-CMs is not necessarily accompanied by ventricular-like expression of all sarcomeric proteins. Our data suggest that hPSC-CMs could provide useful tools for investigating inherited cardiac diseases affecting contractile function during early developmental stages. PMID:29403388

  16. 77 FR 11677 - Medicaid Program; Review and Approval Process for Section 1115 Demonstrations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... experimental, pilot, and demonstration projects approved under section 1115 of the Social Security Act relating... selected provisions of section 1902 of the Act for experimental, pilot, or demonstration projects... application, and recommended that CMS allow the State to not post a complete application. The commenters noted...

  17. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

    PubMed

    Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

    2017-02-07

    Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated state than adipocytes from normal microenvironment. This would indicate a loss of normal functions in mature adipocytes (such as energy storage), in support of others that might favor tumor growth.

  18. Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction.

    PubMed

    Ma, Hong; Wang, Li; Liu, Jiandong; Qian, Li

    2017-01-01

    Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

  19. A search for a heavy Majorana neutrino and a radiation damage simulation for the HF detector

    NASA Astrophysics Data System (ADS)

    Wetzel, James William

    A search for heavy Majorana neutrinos is performed using an event signature defined by two same-sign muons accompanied by two jets. This search is an extension of previous searches, (L3, DELPHI, CMS, ATLAS), using 19.7 fb -1 of data from the 2012 Large Hadron Collider experimental run collected by the Compact Muon Solenoid experiment. A mass window of 40-500 GeV/ c2 is explored. No excess events above Standard Model backgrounds is observed, and limits are set on the mixing element squared, |VmuN|2, as a function of Majorana neutFnrino mass. The Hadronic Forward (HF) Detector's performance will degrade as a function of the number of particles delivered to the detector over time, a quantity referred to as integrated luminosity and measured in inverse femtobarns (fb-1). In order to better plan detector upgrades, the CMS Forward Calorimetry Task Force (FCAL) group and the CMS Hadronic Calorimeter (HCAL) group have requested that radiation damage be simulated and the subsequent performance of the HF subdetector be studied. The simulation was implemented into both the CMS FastSim and CMS FullSim simulation packages. Standard calorimetry performance metrics were computed and are reported. The HF detector can expect to perform well through the planned delivery of 3000 fb-1.

  20. Morphometric analysis of stab wounds by MSCT and MRI after the instillation of contrast medium.

    PubMed

    Fais, Paolo; Cecchetto, Giovanni; Boscolo-Berto, Rafael; Toniolo, Matteo; Viel, Guido; Miotto, Diego; Montisci, Massimo; Tagliaro, Franco; Giraudo, Chiara

    2016-06-01

    To analyze the morphology and depth of stab wounds experimentally produced on human legs amputated for medical reasons using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) after the instillation of a single contrast medium solution (CMS). For morphological analysis, MSCT and MRI scans were performed before and after the instillation of CMS into the wound cavity. Depth measurements were performed on the sagittal view only after CMS instillation. Subsequently, each wound was dissected using the layer-by-layer technique and the depth was measured by a ruler. One-way between-groups pairwise analysis of variance (ANOVA) and Bland-Altman plot analysis were used for comparing radiological and anatomical measurements. Unenhanced MSCT images did not identify the wound channels, whereas unenhanced MRI evidenced the wound cavity in 50 % of cases. After the instillation of CMS, both MSCT and MRI depicted the wound channel in all the investigated stabbings, although the morphology of the cavity was irregular and did not resemble the shape of the blade. The radiological measurements of the wounds' depth, after the application of CMS, exhibited a high level of agreement (about 95 % at Bland-Altman plot analysis) with the anatomical measurements at dissection. A similar systematic underestimation, however, has been evidenced for MSCT (average 11.4 %; 95 % CI 7-17) and MRI (average 9.6 %; 95 % CI 6-13) data after the instillation of CMS with respect to wound dissection measurements. MSCT and MRI after the instillation of CMS can be used for depicting the morphometric features of stab wounds, although depth measurements are affected by a slight systematic underestimation compared to layer-by-layer dissection.

  1. KMR kt-factorization procedure for the description of the LHCb forward hadron-hadron Z0 production at √{ s} = 13TeV

    NASA Astrophysics Data System (ADS)

    Modarres, M.; Masouminia, M. R.; Aminzadeh Nik, R.; Hosseinkhani, H.; Olanj, N.

    2017-09-01

    Quite recently, two sets of new experimental data from the LHCb and the CMS Collaborations have been published, concerning the production of the Z0 vector boson in hadron-hadron collisions with the center-of-mass energy ECM =√{ s} = 13TeV. On the other hand, in our recent work, we have conducted a set of semi-NLO calculations for the production of the electro-weak gauge vector bosons, utilizing the unintegrated parton distribution functions (UPDF) in the frameworks of Kimber-Martin-Ryskin (KMR) or Martin-Ryskin-Watt (MRW) and the kt-factorization formalism, concluding that the results of the KMR scheme are arguably better in describing the existing experimental data, coming from D0, CDF, CMS and ATLAS Collaborations. In the present work, we intend to follow the same semi-NLO formalism and calculate the rate of the production of the Z0 vector boson, utilizing the UPDF of KMR within the dynamics of the recent data. It will be shown that our results are in good agreement with the new measurements of the LHCb and the CMS Collaborations.

  2. A comparison of NNLO QCD predictions with 7 TeV ATLAS and CMS data for V+jet processes

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

    Boughezal, Radja; Liu, Xiaohui; Petriello, Frank

    2016-06-17

    Here, we perform a detailed comparison of next-to-next-to-leading order (NNLO) QCD predictions for the W+jet and Z+jet processes with 7 TeV experimental data from ATLAS and CMS. We observe excellent agreement between theory and data for most studied observables, which span several orders of magnitude in both cross section and energy. For some observables, such as the HT distribution, the NNLO QCD corrections are essential for resolving existing discrepancies between theory and data.

  3. Noise Reduction Effect of Multiple-Sampling-Based Signal-Readout Circuits for Ultra-Low Noise CMOS Image Sensors.

    PubMed

    Kawahito, Shoji; Seo, Min-Woong

    2016-11-06

    This paper discusses the noise reduction effect of multiple-sampling-based signal readout circuits for implementing ultra-low-noise image sensors. The correlated multiple sampling (CMS) technique has recently become an important technology for high-gain column readout circuits in low-noise CMOS image sensors (CISs). This paper reveals how the column CMS circuits, together with a pixel having a high-conversion-gain charge detector and low-noise transistor, realizes deep sub-electron read noise levels based on the analysis of noise components in the signal readout chain from a pixel to the column analog-to-digital converter (ADC). The noise measurement results of experimental CISs are compared with the noise analysis and the effect of noise reduction to the sampling number is discussed at the deep sub-electron level. Images taken with three CMS gains of two, 16, and 128 show distinct advantage of image contrast for the gain of 128 (noise(median): 0.29 e - rms ) when compared with the CMS gain of two (2.4 e - rms ), or 16 (1.1 e - rms ).

  4. Noise Reduction Effect of Multiple-Sampling-Based Signal-Readout Circuits for Ultra-Low Noise CMOS Image Sensors

    PubMed Central

    Kawahito, Shoji; Seo, Min-Woong

    2016-01-01

    This paper discusses the noise reduction effect of multiple-sampling-based signal readout circuits for implementing ultra-low-noise image sensors. The correlated multiple sampling (CMS) technique has recently become an important technology for high-gain column readout circuits in low-noise CMOS image sensors (CISs). This paper reveals how the column CMS circuits, together with a pixel having a high-conversion-gain charge detector and low-noise transistor, realizes deep sub-electron read noise levels based on the analysis of noise components in the signal readout chain from a pixel to the column analog-to-digital converter (ADC). The noise measurement results of experimental CISs are compared with the noise analysis and the effect of noise reduction to the sampling number is discussed at the deep sub-electron level. Images taken with three CMS gains of two, 16, and 128 show distinct advantage of image contrast for the gain of 128 (noise(median): 0.29 e−rms) when compared with the CMS gain of two (2.4 e−rms), or 16 (1.1 e−rms). PMID:27827972

  5. Impact of the LHC beam abort kicker prefire on high luminosity insertion and CMS detector performance

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

    A.I. Drozhdin, N.V. Mokhov and M. Huhtinen

    1999-04-13

    The effect of possible accidental beam loss in LHC on the IP5 insertion elements and CMS detector is studied via realistic Monte Carlo simulations. Such beam loss could be the consequence of an unsynchronized abort or in worst case an accidental prefire of one of the abort kicker modules. Simulations with the STRUCT code show that this beam losses would take place in the IP5 inner and outer triplets. MARS simulations of the hadronic and electro-magnetic cascades induced in such an event indicate severe heating of the inner triplet quadrupoles. In order to protect the IP5 elements, two methods aremore » proposed: a set of shadow collimators in the outer triplet and a prefired module compensation using a special module charged with an opposite voltage (antikicker). The remnants of the accidental beam loss entering the experimental hall have been used as input for FLUKA simulations in the CMS detector. It is shown that it is vital to take measures to reliably protect the expensive CMS tracker components.« less

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

    Hong, A.; Mariwala, R.K.; Kane, M.S.

    Experimental evidence is provided for adsorptive shape selectivity in the separation of the azeotrope between HF and 1,1,1,2-tetrafluoroethane (134a) over pyrolyzed poly(furfuryl alcohol)-derived carbogenic molecular sieve (PPFA-CMS). The separation can be accomplished over coconut charcoal or Carbosieve G on the basis of the differences in the extent of equilibrium adsorption of HF and 134a. On these adsorbents 134a is more strongly bound than HF, thus it elutes much more slowly from the bed. The heat of adsorption for 134a in the vicinity of 200 C on Carbosieve G is {approximately}8.8 kcal/mol. In contrast, when the same azeotropic mixture is separatedmore » over PPFA-CMS prepared at 500 C, 134a is not adsorbed. As a result 134a elutes from the bed first, followed by HF. The reversal is brought about by the narrower pore size and pore size distribution of the PPFA-CMS versus that for Carbosieve G. Thus the separation over PPFA-CMS is an example of adsorbate shape selectivity and represents a limiting case of kinetic separation.« less

  7. [Study on incorporation of "management and guidance of home-visiting by a pharmacist" into a care plan -observation based on a survey of care managers-].

    PubMed

    Nanaumi, Yoko; Onda, Mitsuko; Sakurai, Hidehiko; Tanaka, Rie; Tsubota, Kenichi; Matoba, Shunya; Mukai, Yusuke; Arakawa, Yukio; Hayase, Yukitoshi

    2010-11-01

    A survey of care managers ("CMs") was conducted to identify top priority issues in promoting the management and guidance of home-visiting by a pharmacist ("management and guidance") by focusing on the experience in incorporating the management and guidance into a care plan and its relevant factors. Major survey items included (1) number of years working as a CM, (2) basic occupation, (3) experience in incorporating the management and guidance into care plans, (4) understanding the management and guidance content, and (5) an awareness of the need for pharmacists' involvement in care plans. A χ² test was conducted to determine if the experience in incorporating the management and guidance into care plans caused a difference in the distribution of the number of years as a CM, the basic occupation, understanding of the management and guidance content, and an awareness of the need for pharmacists' involvement in care plans. A regression analysis was conducted to determine the degree of association between the incorporation experience and each item. The numbers of years working as a CM, the basic occupation, understanding of the management and guidance content, and an awareness of the need for pharmacists' involvement in care plans, were found to be associated with the experience in incorporating the management and guidance into care plans. Understanding of the management and guidance content was most closely associated. To promote pharmacists' management and guidance for home-based care, CMs need to deepen their understanding of this service.

  8. 42 CFR 431.424 - Evaluation requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

  9. 42 CFR 431.424 - Evaluation requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

  10. 42 CFR 431.424 - Evaluation requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

  11. Health services research in the public healthcare system in Hong Kong: an analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data.

    PubMed

    Wong, Martin C S; Jiang, Johnny Y; Tang, Jin-ling; Lam, Augustine; Fung, Hong; Mercer, Stewart W

    2008-06-25

    Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example. Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients' demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients' demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > or = 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients.

  12. Innovative Oncology Care Models Improve End-Of-Life Quality, Reduce Utilization And Spending.

    PubMed

    Colligan, Erin Murphy; Ewald, Erin; Ruiz, Sarah; Spafford, Michelle; Cross-Barnet, Caitlin; Parashuram, Shriram

    2017-03-01

    Three models that received Health Care Innovation Awards from the Centers for Medicare and Medicaid Services (CMS) aimed to reduce the cost and use of health care services and improve the quality of care for Medicare beneficiaries with cancer. Each emphasized a different principle: the oncology medical home, patient navigation, or palliative care. Comparing participants in each model who died during the study period to matched comparators, we found that the oncology medical home and patient navigation models were associated with decreased costs in the last ninety days of life ($3,346 and $5,824 per person, respectively) and fewer hospitalizations in the last thirty days of life (fifty-seven and forty per 1,000 people, respectively). The patient navigation model was also associated with fewer emergency department visits in the last thirty days of life and increased hospice enrollment in the last two weeks of life. These promising results can inform new initiatives for cancer patients, such as the CMS Oncology Care Model. Project HOPE—The People-to-People Health Foundation, Inc.

  13. The Comprehensive Primary Care Initiative: Effects On Spending, Quality, Patients, And Physicians.

    PubMed

    Peikes, Deborah; Dale, Stacy; Ghosh, Arkadipta; Taylor, Erin Fries; Swankoski, Kaylyn; O'Malley, Ann S; Day, Timothy J; Duda, Nancy; Singh, Pragya; Anglin, Grace; Sessums, Laura L; Brown, Randall S

    2018-06-01

    The Comprehensive Primary Care Initiative (CPC), a health care delivery model developed by the Centers for Medicare and Medicaid Services (CMS), tested whether multipayer support of 502 primary care practices across the country would improve primary care delivery, improve care quality, or reduce spending. We evaluated the initiative's effects on care delivery and outcomes for fee-for-service Medicare beneficiaries attributed to initiative practices, relative to those attributed to matched comparison practices. CPC practices reported improvements in primary care delivery, including care management for high-risk patients, enhanced access, and improved coordination of care transitions. The initiative slowed growth in emergency department visits by 2 percent in CPC practices, relative to comparison practices. However, it did not reduce Medicare spending enough to cover care management fees or appreciably improve physician or beneficiary experience or practice performance on a limited set of Medicare claims-based quality measures. As CMS and other payers increasingly use alternative payment models that reward quality and value, CPC provides important lessons about supporting practices in transforming care.

  14. The QuarkNet CMS masterclass: bringing the LHC to students

    NASA Astrophysics Data System (ADS)

    Cecire, Kenneth; McCauley, Thomas

    2016-04-01

    QuarkNet is an educational program which brings high school teachers and their students into the particle physics research community. The program supports research experiences and professional development workshops and provides inquiry-oriented investigations, some using real experimental data. The CMS experiment at the LHC has released several thousand proton-proton collision events for use in education and outreach. QuarkNet, in collaboration with CMS, has developed a physics masterclass and e-Lab based on this data. A masterclass is a day-long educational workshop where high school students travel to nearby universities and research laboratories. There they learn from LHC physicists about the basics of particle physics and detectors. They then perform a simple measurement using LHC data, and share their results with other students around the world via videoconference. Since 2011 thousands of students from over 25 countries have participated in the CMS masterclass as organized by QuarkNet and the International Particle Physics Outreach Group (IPPOG).We describe here the masterclass exercise: the physics, the online event display and database preparation behind it, the measurement the students undertake, their results and experiences, and future plans for the exercise.

  15. Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model

    PubMed Central

    Shiba, Yuji; Filice, Dominic; Fernandes, Sarah; Minami, Elina; Dupras, Sarah K.; Van Biber, Benjamin; Trinh, Peter; Hirota, Yusuke; Gold, Joseph D.; Viswanathan, Mohan; Laflamme, Michael A.

    2014-01-01

    Background Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following their direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury. Methods & Results At 28 days following cardiac cryoinjury, guinea pigs underwent intra-cardiac injection of hESC-CMs, non-cardiac hESC-derivatives (non-CMs) or vehicle. Histology confirmed partial remuscularization of the infarct zone in hESC-CM recipients, while non-CM recipients showed heterogeneous xenografts. The three experimental groups showed no significant difference in the left ventricular dimensions or fractional shortening by echocardiography or in the incidence of spontaneous arrhythmias by telemetric monitoring. While recipients of hESC-CMs and vehicle showed a similar incidence of arrhythmias induced by programmed electrical stimulation at 4-weeks post-transplantation, non-CM recipients proved to be highly inducible, with a ~3-fold greater incidence of induced arrhythmias. In parallel studies, we investigated the ability of hESC-CMs to couple with host myocardium in chronically injured hearts by the intravital imaging of hESC-CM grafts that stably expressed a fluorescent reporter of graft activation, the genetically-encoded calcium sensor GCaMP3. In this work, we found that only ~38% (5 of 13) of recipients of GCaMP3+ hESC-CMs showed fluorescent transients that were coupled to the host electrocardiogram. Conclusions hESC-CMs engraft in chronically injured hearts without increasing the incidence of arrhythmias, but their electromechanical integration is more limited than was previously reported following their transplantation in a subacute injury model. Moreover, non-CM grafts may promote arrhythmias under certain conditions, a finding that underscores the need for input preparations of high cardiac purity. PMID:24516260

  16. Results of a higgs boson searches in the ATLAS and CMS experiments at the large hadron collider at energies 7 and 8 TeV

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

    Artamonov, A. A.; Epshteyn, V. S.; Gavrilov, V. B.

    2016-05-15

    Recent achievements of the ATLAS and CMS experiments at the Large Hadron Collider searching for a Higgs boson are summarized. A new particle with the mass of 125 GeV and properties expected for the Standard Model Higgs boson was discovered three years ago in these experiments in proton-proton collisions when analyzing part of the data taken at the centre-of-mass energies 7 TeV and 8 TeV in 2011 and 2012 year exposures. Today all the data are processed and fully analyzed. Experimental results of studies of individual Higgs boson decay channels as well as their combination to extract such properties asmore » mass, signal strength, coupling constants, spin and parity are reviewed. All experimental results are found to be compatible with the Standard Model predictions.« less

  17. The quality of Medicaid and Medicare data obtained from CMS and its contractors: implications for pharmacoepidemiology.

    PubMed

    Leonard, Charles E; Brensinger, Colleen M; Nam, Young Hee; Bilker, Warren B; Barosso, Geralyn M; Mangaali, Margaret J; Hennessy, Sean

    2017-04-26

    Administrative claims of United States Centers for Medicare and Medicaid Services (CMS) beneficiaries have long been used in non-experimental research. While CMS performs in-house checks of these claims, little is known of their quality for conducting pharmacoepidemiologic research. We performed exploratory analyses of the quality of Medicaid and Medicare data obtained from CMS and its contractors. Our study population consisted of Medicaid beneficiaries (with and without dual coverage by Medicare) from California, Florida, New York, Ohio, and Pennsylvania. We obtained and compiled 1999-2011 data from these state Medicaid programs (constituting about 38% of nationwide Medicaid enrollment), together with corresponding national Medicare data for dually-enrolled beneficiaries. This descriptive study examined longitudinal patterns in: dispensed prescriptions by state, by quarter; and inpatient hospitalizations by federal benefit, state, and age group. We further examined discrepancies between demographic characteristics and disease states, in particular frequencies of pregnancy complications among men and women beyond childbearing age, and prostate cancers among women. Dispensed prescriptions generally increased steadily and consistently over time, suggesting that these claims may be complete. A commercially-available National Drug Code lookup database was able to identify the dispensed drug for 95.2-99.4% of these claims. Because of co-coverage by Medicare, Medicaid data appeared to miss a substantial number of hospitalizations among beneficiaries ≥ 45 years of age. Pregnancy complication diagnoses were rare in males and in females ≥ 60 years of age, and prostate cancer diagnoses were rare in females. CMS claims from five large states obtained directly from CMS and its contractors appeared to be of high quality. Researchers using Medicaid data to study hospital outcomes should obtain supplemental Medicare data on dual enrollees, even for non-elders. Not applicable.

  18. Effect of Wind Velocity on Flame Spread in Microgravity

    NASA Technical Reports Server (NTRS)

    Prasad, Kuldeep; Olson, Sandra L.; Nakamura, Yuji; Fujita, Osamu; Nishizawa, Katsuhiro; Ito, Kenichi; Kashiwagi, Takashi; Simons, Stephen N. (Technical Monitor)

    2002-01-01

    A three-dimensional, time-dependent model is developed describing ignition and subsequent transition to flame spread over a thermally thin cellulosic sheet heated by external radiation in a microgravity environment. A low Mach number approximation to the Navier Stokes equations with global reaction rate equations describing combustion in the gas phase and the condensed phase is numerically solved. The effects of a slow external wind (1-20 cm/s) on flame transition are studied in an atmosphere of 35% oxygen concentration. The ignition is initiated at the center part of the sample by generating a line-shape flame along the width of the sample. The calculated results are compared with data obtained in the 10s drop tower. Numerical results exhibit flame quenching at a wind speed of 1.0 cm/s, two localized flames propagating upstream along the sample edges at 1.5 cm/s, a single line-shape flame front at 5.0 cm/s, three flames structure observed at 10.0 cm/s (consisting of a single line-shape flame propagating upstream and two localized flames propagating downstream along sample edges) and followed by two line-shape flames (one propagating upstream and another propagating downstream) at 20.0 cm/s. These observations qualitatively compare with experimental data. Three-dimensional visualization of the observed flame complex, fuel concentration contours, oxygen and reaction rate isosurfaces, convective and diffusive mass flux are used to obtain a detailed understanding of the controlling mechanism, Physical arguments based on lateral diffusive flux of oxygen, fuel depletion, oxygen shadow of the flame and heat release rate are constructed to explain the various observed flame shapes.

  19. Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy

    PubMed Central

    Prajapati, Chandra

    2018-01-01

    ABSTRACT Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general. PMID:29361520

  20. CMS changes in reimbursement for HAIs: setting a research agenda.

    PubMed

    Stone, Patricia W; Glied, Sherry A; McNair, Peter D; Matthes, Nikolas; Cohen, Bevin; Landers, Timothy F; Larson, Elaine L

    2010-05-01

    The Centers for Medicare and Medicaid Services (CMS) promulgated regulations commencing October 1, 2008, which deny payment for selected conditions occurring during the hospital stay and are not present on admission. Three of the 10 hospital-acquired conditions covered by the new CMS policy involve healthcare-associated infections, which are a common, expensive, and often preventable cause of inpatient morbidity and mortality. To outline a research agenda on the impact of CMS's payment policy on the healthcare system and the prevention of healthcare-associated infections. An invitational day-long conference was convened in April 2009. Including the planning committee and speakers there were 41 conference participants who were national experts and senior researchers. Building upon a behavioral model and organizational theory and management research a conceptual framework was applied to organize the wide range of issues that arose. A broad array of research topics was identified. Thirty-two research agenda items were organized in the areas of incentives, environmental factors, organizational factors, clinical outcomes, staff outcomes, and financial outcomes. Methodological challenges are also discussed. This policy is a first significant step to move output-based inpatient funding to outcome-based funding, and this agenda is applicable to all hospital-acquired conditions. Studies beginning soon will have the best hope of capturing data for the years preceding the policy change, a key element in non-experimental research. The CMS payment policy offers an excellent opportunity to understand and influence the use of financial incentives for improving patient safety.

  1. Telocytes and putative stem cells in ageing human heart

    PubMed Central

    Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

    2015-01-01

    Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit http://www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days–1 year), children (6–17 years) and adults (34–60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52–62%; vascular smooth muscle cells and pericytes 22–28%, Schwann cells with nerve endings 6–7%, fibroblasts 3–10%, macrophages 1–8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults). PMID:25545142

  2. Cardiomyogenic Differentiation of Human Dental Follicle-derived Stem Cells by Suberoylanilide Hydroxamic Acid and Their In Vivo Homing Property.

    PubMed

    Sung, Iel-Yong; Son, Han-Na; Ullah, Imran; Bharti, Dinesh; Park, Ju-Mi; Cho, Yeong-Cheol; Byun, June-Ho; Kang, Young-Hoon; Sung, Su-Jin; Kim, Jong-Woo; Rho, Gyu-Jin; Park, Bong-Wook

    2016-01-01

    The purpose of the present study was to investigate the in vitro cardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze the in vivo homing capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential. Adding SAHA to the culture medium induced the successful in vitro differentiation of DFCs into cardiomyocytes. These iCMs expressed cardiomyogenic markers, including alpha-smooth muscle actin (α-SMA), cardiac muscle troponin T (TNNT2), Desmin, and cardiac muscle alpha actin (ACTC1) , at both the mRNA and protein level. For the assessment of homing capacity, PKH26 labeled iCMs were intraperitoneally injected (1×10 6 cells in 100 µL of PBS) into the experimental mice, and the ratios of PKH26 positive cells to the total number of injected cells, in multiple organs were determined. The calculated homing ratios, 14 days after systemic cell transplantation, were 5.6 ± 1.0%, 3.6 ± 1.1%, and 11.6 ± 2.7% in heart, liver, and kidney respectively. There was no difference in the serum levels of interleukin-2 and interleukin-10 at 14 days after transplantation, between the experimental (iCM injected) and control (no injection or PBS injection) groups. These results demonstrate that DFCs can be an excellent source for cardiomyocyte differentiation and regeneration. Moreover, the iCMs can be delivered into heart muscle via systemic administration without eliciting inflammatory or immune response. This can serve as the pilot study for further investigations into the in vitro cardiomyogenic differentiation potential of DFCs under the influence of SAHA and the in vivo homing capacity of the iCMs into the heart muscle, when injected systemically.

  3. Hemodialysis Hospitalizations and Readmissions: The Effects of Payment Reform

    PubMed Central

    Erickson, Kevin F.; Winkelmayer, Wolfgang C.; Chertow, Glenn M.; Bhattacharya, Jay

    2016-01-01

    Background In 2004 the Centers for Medicare & Medicaid Services (CMS) changed reimbursement for physicians and advanced practitioners caring for patients receiving hemodialysis from a capitated to a tiered fee-for-service system, encouraging increased face-to-face visits. This early version of a pay-for-performance initiative targeted a care process: more frequent provider visits in hemodialysis. While more frequent provider visits in hemodialysis are associated with fewer hospitalizations and re-hospitalizations, it is unknown whether encouraging more frequent visits through reimbursement policy also yielded these benefits. Study Design We used a retrospective cohort, interrupted time-series study design to examine whether the 2004 nephrologist reimbursement reform led to reduced hospitalizations and re-hospitalizations. We also used published data to estimate a range of annual economic costs associated with more frequent visits. Setting & Participants Medicare beneficiaries in the United States receiving hemodialysis in the two years prior to and following reimbursement reform. Predictor The two years following nephrologist reimbursement reform. Outcomes Odds of hospitalization and 30-day hospital readmission for all causes and fluid overload; US dollars. Results We found no significant change in all-cause hospitalization or re-hospitalization, and slight reductions in hospitalization and re-hospitalization for fluid overload following reimbursement reform; the estimated economic cost associated with additional visits ranged from $13 to $87 million per year, depending on who (physicians or advanced practitioners) spent additional time visiting patients and how much additional effort was involved. Limitations Due to limited information about how much additional time providers spent seeing patients after reimbursement reform, we could only examine a range of potential economic costs associated with the reform. Conclusions A Medicare reimbursement policy designed to encourage more frequent visits during outpatient hemodialysis may have been costly. The policy was associated with fewer hospitalizations and re-hospitalizations for fluid overload, but had no effect on all-cause hospitalizations or re-hospitalizations. PMID:27856087

  4. Identification of Emergency Department Visits in Medicare Administrative Claims: Approaches and Implications.

    PubMed

    Venkatesh, Arjun K; Mei, Hao; Kocher, Keith E; Granovsky, Michael; Obermeyer, Ziad; Spatz, Erica S; Rothenberg, Craig; Krumholz, Harlan M; Lin, Zhenqui

    2017-04-01

    Administrative claims data sets are often used for emergency care research and policy investigations of healthcare resource utilization, acute care practices, and evaluation of quality improvement interventions. Despite the high profile of emergency department (ED) visits in analyses using administrative claims, little work has evaluated the degree to which existing definitions based on claims data accurately captures conventionally defined hospital-based ED services. We sought to construct an operational definition for ED visitation using a comprehensive Medicare data set and to compare this definition to existing operational definitions used by researchers and policymakers. We examined four operational definitions of an ED visit commonly used by researchers and policymakers using a 20% sample of the 2012 Medicare Chronic Condition Warehouse (CCW) data set. The CCW data set included all Part A (hospital) and Part B (hospital outpatient, physician) claims for a nationally representative sample of continuously enrolled Medicare fee-for-services beneficiaries. Three definitions were based on published research or existing quality metrics including: 1) provider claims-based definition, 2) facility claims-based definition, and 3) CMS Research Data Assistance Center (ResDAC) definition. In addition, we developed a fourth operational definition (Yale definition) that sought to incorporate additional coding rules for identifying ED visits. We report levels of agreement and disagreement among the four definitions. Of 10,717,786 beneficiaries included in the sample data set, 22% had evidence of ED use during the study year under any of the ED visit definitions. The definition using provider claims identified a total of 4,199,148 ED visits, the facility definition 4,795,057 visits, the ResDAC definition 5,278,980 ED visits, and the Yale definition 5,192,235 ED visits. The Yale definition identified a statistically different (p < 0.05) collection of ED visits than all other definitions including 17% more ED visits than the provider definition and 2% fewer visits than the ResDAC definition. Differences in ED visitation counts between each definition occurred for several reasons including the inclusion of critical care or observation services in the ED, discrepancies between facility and provider billing regulations, and operational decisions of each definition. Current operational definitions of ED visitation using administrative claims produce different estimates of ED visitation based on the underlying assumptions applied to billing data and data set availability. Future analyses using administrative claims data should seek to validate specific definitions and inform the development of a consistent, consensus ED visitation definitions to standardize research reporting and the interpretation of policy interventions. © 2016 by the Society for Academic Emergency Medicine.

  5. Identification of Emergency Department Visits in Medicare Administrative Claims: Approaches and Implications

    PubMed Central

    Venkatesh, Arjun K.; Mei, Hao; Kocher, Keith E.; Granovsky, Michael; Obermeyer, Ziad; Spatz, Erica S.; Rothenberg, Craig; Krumholz, Harlan M.; Lin, Zhenqui

    2018-01-01

    Objectives Administrative claims data sets are often used for emergency care research and policy investigations of healthcare resource utilization, acute care practices, and evaluation of quality improvement interventions. Despite the high profile of emergency department (ED) visits in analyses using administrative claims, little work has evaluated the degree to which existing definitions based on claims data accurately captures conventionally defined hospital-based ED services. We sought to construct an operational definition for ED visitation using a comprehensive Medicare data set and to compare this definition to existing operational definitions used by researchers and policymakers. Methods We examined four operational definitions of an ED visit commonly used by researchers and policymakers using a 20% sample of the 2012 Medicare Chronic Condition Warehouse (CCW) data set. The CCW data set included all Part A (hospital) and Part B (hospital outpatient, physician) claims for a nationally representative sample of continuously enrolled Medicare fee-for-services beneficiaries. Three definitions were based on published research or existing quality metrics including: 1) provider claims–based definition, 2) facility claims–based definition, and 3) CMS Research Data Assistance Center (ResDAC) definition. In addition, we developed a fourth operational definition (Yale definition) that sought to incorporate additional coding rules for identifying ED visits. We report levels of agreement and disagreement among the four definitions. Results Of 10,717,786 beneficiaries included in the sample data set, 22% had evidence of ED use during the study year under any of the ED visit definitions. The definition using provider claims identified a total of 4,199,148 ED visits, the facility definition 4,795,057 visits, the ResDAC definition 5,278,980 ED visits, and the Yale definition 5,192,235 ED visits. The Yale definition identified a statistically different (p < 0.05) collection of ED visits than all other definitions including 17% more ED visits than the provider definition and 2% fewer visits than the ResDAC definition. Differences in ED visitation counts between each definition occurred for several reasons including the inclusion of critical care or observation services in the ED, discrepancies between facility and provider billing regulations, and operational decisions of each definition. Conclusion Current operational definitions of ED visitation using administrative claims produce different estimates of ED visitation based on the underlying assumptions applied to billing data and data set availability. Future analyses using administrative claims data should seek to validate specific definitions and inform the development of a consistent, consensus ED visitation definitions to standardize research reporting and the interpretation of policy interventions. PMID:27864915

  6. Evaluation of Pharmacists' Work in a Physician-Pharmacist Collaborative Model for the Management of Hypertension.

    PubMed

    Isetts, Brian J; Buffington, Daniel E; Carter, Barry L; Smith, Marie; Polgreen, Linnea A; James, Paul A

    2016-04-01

    Physician-pharmacist collaborative models have been shown to improve the care of patients with numerous chronic medical conditions. Team-based health care using integrated clinical pharmacists provides one opportunity to improve quality in health care systems that use population-based financing. In November 2015, the Centers for Medicare and Medicaid Services (CMS) requested that the relative value of pharmacists' work in team-based care needs to be established. Thus the objective of this study was to describe the components of pharmacists' work in the management of hypertension with a physician-pharmacist collaborative model. Descriptive analysis of the components of pharmacists' work in the Collaboration Among Pharmacists and Physicians to Improve Outcomes Now (CAPTION) study, a prospective, cluster randomized trial. This analysis was intended to provide policymakers with data and information, using the CAPTION study model, on the time and intensity of pharmacists' work to understand pharmacists' relative value contributions in the context of CMS financing and population management aims. The CAPTION trial was conducted in 32 community-based medical offices in 15 U.S. states and included 390 patients with multiple cardiovascular risk factors. Blood pressure was measured by trained study coordinators in each office, and patients were included in the study if they had uncontrolled blood pressure. Included patients were randomized to a 9-month intervention, a 24-month intervention, or usual care. The goal of the pharmacist intervention was to improve blood pressure control and resolve drug therapy problems impeding progress toward blood pressure goals. This intervention included medical record review, a structured assessment with the patient, collaboration to achieve goals of therapy, and patient follow-up. The two intervention arms (9 and 24 mo) were identical the first 9 months, and that time frame is the focus of this workload evaluation. Pharmacists completed study encounter forms for every patient encounter and estimated time spent in pre-visit, face-to-face care, and post-visit activities. Among the 390 patients, there were 2811 encounters with pharmacists that involved 3.44 hours/patient for face-to-face care visits plus 1.55 hours/patient for pre-visit and post-visit work. Intensity of work was reflected in interventions to resolve drug therapy problems with patients (43% of encounters) and with physicians (1169 recommendations, of which physicians accepted 1153 [98.6%]), resulting in improvement of patients' blood pressure goals achieved (from 0% at baseline to 43% at 9 months based on the primary study end point). Pharmacists provided extensive interventions to patients with hypertension. This analysis provides a framework for health systems, provider groups, and payers to measure pharmacists' work in value-based financing and population management. © 2016 Pharmacotherapy Publications, Inc.

  7. Evaluation of Pharmacists’ Work in a Physician-Pharmacist Collaborative Model for the Management of Hypertension

    PubMed Central

    Isetts, Brian J.; Buffington, Daniel E.; Carter, Barry L.; Smith, Marie; Polgreen, Linnea A.; James, Paul A.

    2016-01-01

    Study Objective Physician-pharmacist collaborative models have been shown to improve the care of patients with numerous chronic medical conditions. Team-based health care using integrated clinical pharmacists provides one opportunity to improve quality in health care systems that use population-based financing. In November 2015, the Centers for Medicare and Medicaid Services (CMS) requested that the relative value of pharmacists’ work in team-based care needs to be established. Thus, the objective of this study was to describe the components of pharmacists’ work in the management of hypertension with a physician-pharmacist collaborative model. Design Descriptive analysis of the components of pharmacists’ work in the Collaboration Among Pharmacists and Physicians To Improve Outcomes Now (CAPTION) study, a prospective, cluster randomized trial. Measurements and Main Results This analysis was intended to provide policymakers with data and information, using the CAPTION study model, on the time and intensity of pharmacists’ work to understand pharmacists’ relative value contributions in the context of CMS financing and population management aims. The CAPTION trial was conducted in 32 community-based medical offices in 15 U.S. states and included 390 patients with multiple cardiovascular risk factors. Blood pressure was measured by trained study coordinators in each office, and patients were included in the study if they had uncontrolled blood pressure. Included patients were randomized to a 9-month intervention, a 24-month intervention, or usual care. The goal of the pharmacist intervention was to improve blood pressure control and resolve drug therapy problems impeding progress toward blood pressure goals. This intervention included medical record review, a structured assessment with the patient, collaboration to achieve goals of therapy, and patient follow-up. The two intervention arms (9 months and 24 months) were identical the first 9 months, and that time frame is the focus of this workload evaluation. Pharmacists completed study encounter forms for every patient encounter and estimated time spent in pre-visit, face-to-face care, and post-visit activities. Among the 390 patients, there were 2,811 encounters with pharmacists that involved 3.44 hours/patient for face-to-face care visits plus 1.55 hours/patient for pre-visit and post-visit work. Intensity of work was reflected in interventions to resolve drug therapy problems with patients (43% of encounters) and with physicians (1,169 recommendations, of which physicians accepted 1,153 [98.6%]), resulting in improvement of patients’ blood pressure goals achieved (from 0% at baseline to 43% at 9 months based on the primary study endpoint). Conclusion Pharmacists provided extensive interventions to patients with hypertension. This analysis provides a framework for health systems, provider groups, and payers to measure pharmacists’ work in value-based financing and population management. PMID:26893135

  8. Systematic evidence-based quality measurement life-cycle approach to measure retirement in CHIPRA.

    PubMed

    Dougherty, Denise; Mistry, Kamila B; Lindly, Olivia; Desoto, Maushami; LLanos, Karen; Chesley, Francis

    2014-01-01

    In 2009, Centers for Medicare and Medicaid Services (CMS) publicly released an initial child core set (CCS) of health care quality measures for voluntary reporting by state Medicaid and Children's Health Insurance Program (CHIP) programs. CMS is responsible for implementing the reporting program and for updating the CCS annually. We assessed selected CCS measures for potential retirement. We identified a 23-member external advisory group to provide relevant expertise. We worked with the group to identify 4 major criteria with multiple subcomponents for assessing the measures. We provided information corresponding to each criterion and subcriterion, using a variety of sources such as the 2009 Medicaid Analytic eXtract (MAX), state-level Medicaid and CHIP data submitted to the CMS, and summaries of published literature on clinical and quality improvement effectiveness related to the CCS topics. Using this information, the group: 1) used a modified Delphi process to score the measures in 2 anonymous scoring rounds (on a scale of 1 to 9 in each round); 2) voted on whether each measure should be retired; and 3) provided narrative explanations of their choices (which formed the basis of our qualitative findings). Recommendations were reviewed by CMS before promulgation to state programs. The Subcommittee of the National Advisory Council on Healthcare Research and Quality (SNAC) recommended that the 4 major criteria be importance, scientific acceptability, feasibility, and usability. The SNAC recommended 3 measures for retirement: access to primary care; testing for strep before recommending antibiotics for pharyngitis; and annual HbA1c testing of children with diabetes. Explanations for suggesting retirement of the measures included: views that the well-visit measures were a better measure of access than the primary care measure; a likely ceiling effect (pharyngitis); and the paucity of clinical evidence and low prevalence (both for HbA1c). CMS recommended that state Medicaid and CHIP programs retire 2 of the recommended measures from the CCS, but retained the access to primary care measure. Periodic reassessment of the value of health care quality measures can reduce reporting burden and allow measure users to focus on measures with higher likelihood of leading to improvements in quality of care and child health outcomes. Published by Elsevier Inc.

  9. Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.

    PubMed

    Jyoti, Kiran; Bhatia, Richa Kaur; Martis, Elvis A F; Coutinho, Evans C; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

    2016-12-01

    In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10 -3 M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Redesign links CMs, primary care.

    PubMed

    2013-12-01

    At WellSpan Health, teams that include hospital-based case managers and social workers, and health coaches located in physician offices, work together to coordinate care. The case managers and social workers are assigned by physician and spend most of their time in the hospital, but are expected to spend a target of two hours a week at the WellSpan Medical Group physician practices. Practices that are not part of the WellSpan Medical Group are assigned a case manager and a social worker who follow their patients in the hospital but do not visit the practice. The initiative promotes communication and collaboration between the hospital level of care and primary care.

  11. Morphological and genetic characterization of a new cytoplasmic male sterility system (oxa CMS) in stem mustard (Brassica juncea).

    PubMed

    Heng, Shuangping; Liu, Sansan; Xia, Chunxiu; Tang, HongYu; Xie, Fei; Fu, Tingdong; Wan, Zhengjie

    2018-01-01

    KEY MESSAGE: oxa CMS is a new cytoplasmic male sterility type in Brassica juncea. oxa CMS is a cytoplasmic male sterility (CMS) line that has been widely used in the production and cultivation of stem mustard in the southwestern China. In this study, different CMS-type specific mitochondrial markers were used to confirm that oxa CMS is distinct from the pol CMS, ogu CMS, nap CMS, hau CMS, tour CMS, Moricandia arvensis CMS, orf220-type CMS, etc., that have been previously reported in Brassica crops. Pollen grains of the oxa CMS line are sterile with a self-fertility rate of almost 0% and the sterility strain rate and sterility degree of oxa CMS is 100% due to a specific flower structure and flowering habit. Scanning electron microscopy revealed that most pollen grains in mature anthers of the oxa CMS line are empty, flat and deflated. Semi-thin section further showed that the abortive stage of anther development in oxa CMS is initiated at the late uninucleate stage. Abnormally vacuolated microspores caused male sterility in the oxa CMS line. This cytological study combined with marker-assisted selection showed that oxa CMS is a novel CMS type in stem mustard (Brassica juncea). Interestingly, the abortive stage of oxa CMS is later than those in other CMS types reported in Brassica crops, and there is no negative effect on the oxa CMS line growth period. This study demonstrated that this novel oxa CMS has a unique flower structure with sterile pollen grains at the late uninucleate stage. Our results may help to uncover the mechanism of oxa CMS in Brassica juncea.

  12. Thermal and chemical evolution in the early Solar System as recorded by FUN CAIs: Part II - Laboratory evaporation of potential CMS-1 precursor material

    NASA Astrophysics Data System (ADS)

    Mendybaev, Ruslan A.; Williams, Curtis D.; Spicuzza, Michael J.; Richter, Frank M.; Valley, John W.; Fedkin, Alexei V.; Wadhwa, Meenakshi

    2017-03-01

    We present the results of laboratory experiments in which a forsterite-rich melt estimated to be a potential precursor of Allende CMS-1 FUN CAI was evaporated into vacuum for different lengths of time at 1900 °C. The evaporation of this melt resulted in residues that define trajectories in chemical as well as magnesium, silicon and oxygen isotopic composition space and come very close to the measured properties of CMS-1. The isotopic composition of the evaporation residues was also used to determine the kinetic isotopic fractionation factors [α2,1 (vapor-melt) defined as the ratio of isotopes 2 and 1 of a given element in the evaporating gas divided by their ratio in the evaporating source] for evaporation of magnesium (α25,24 for 25Mg/24Mg), silicon (α29,28 for 29Si/28Si) and oxygen (α18,16 for 18O/16O) from the forsterite-rich melt at 1900 °C. The values of α25,24 = 0.98383 ± 0.00033 and α29,28 = 0.99010 ± 0.00038 are essentially independent of change in the melt composition as evaporation proceeds. In contrast, α18,16 changes from 0.9815 ± 0.0016 to ∼0.9911 when the residual melt composition changes from forsteritic to melilitic. Using the determined values of α25,24 and α29,28 and present-day bulk chemical composition of the CMS-1, the composition of the precursor of the inclusion was estimated to be close to the clinopyroxene + spinel + forsterite assemblage condensed from a solar composition gas. The correspondence between the chemical composition and isotopic fractionation of experimental evaporation residues and the present-day bulk chemical and isotopic compositions of CMS-1 is evidence that evaporation played a major role in the chemical evolution of CMS-1.

  13. Human induced pluripotent stem cell‐derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block

    PubMed Central

    Paci, M; Hyttinen, J; Rodriguez, B

    2015-01-01

    Background and Purpose Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and in silico human adult ventricular cardiomyocyte (hAdultV‐CM) models. Their combination was recently proposed as a potential replacement for the present hERG‐based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC‐CM and hAdultV‐CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. Experimental Approach In silico AP models of ventricular‐like and atrial‐like hiPSC‐CMs and hAdultV‐CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. Key Results Qualitatively, hiPSC‐CM and hAdultV‐CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC‐CMs were more sensitive to block of (i) L‐type Ca2+ currents due to the overexpression of the Na+/Ca2+ exchanger (leading to shorter APs) and (ii) the inward rectifier K+ current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). Conclusions and Implications In silico hiPSC‐CMs and hAdultV‐CMs exhibit a similar response to selective current blocks. However, overall hiPSC‐CMs show greater sensitivity to block, which may facilitate in vitro identification of drug‐induced effects. Extrapolation of drug effects from hiPSC‐CM to hAdultV‐CM and pro‐arrhythmic risk assessment can be facilitated by in silico predictions using biophysically‐based computational models. PMID:26276951

  14. Asthma medication ratio predicts emergency department visits and hospitalizations in children with asthma.

    PubMed

    Andrews, Annie Lintzenich; Simpson, Annie N; Basco, William T; Teufel, Ronald J

    2013-01-01

    To determine if the asthma medication ratio predicts subsequent emergency department (ED) visits and hospital admissions in children. Retrospective cohort with two year pairs. 2007-2009 South Carolina Medicaid recipients with persistent asthma age 2-18. Controller-to-total asthma medication ratios were calculated for each patient in 2007 and 2008. Ratios range from 0-1 (1 = ideal, 0 = no controller). 2008 and 2009 asthma related ED visits, hospitalizations, and a combined outcome of ED visit or hospitalization in the subsequent 3, 6, and 12 month time periods. 19,512 patients were included. Mean age 8.9 years, 58% male, and 55% black. The ratio significantly predicted ED visits and hospitalizations over subsequent 3, 6, and 12 month time periods. The cut-point that maximized the ability to predict visits ranged from 0.4-0.6. A cutpoint of 0.5 was used in the final models. After controlling for age, race, gender, and rurality, patients with a ratio <0.5 were significantly more likely to have a subsequent emergent healthcare visit (OR 1.5-2.0). The ratio retained its predictive ability in both year-pairs for all three outcome variables, in all three time periods, with the exception of the 2008 ratio not predicting 2009 3-month and 6-month hospitalizations. The asthma medication ratio is a significant predictor of ED visits and hospitalizations in children. Using a cutoff of <0.5 to signal at-risk patients may be an effective way for populations who would benefit from increased use of controller medications to reduce future emergent asthma visits. CPT only copyright XXXX-2012 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association. Applicable FARS/DFARS Apply to Government Use. Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. See attached CMS CPT 2013 end user license.

  15. Detection of the Diversity of Cytoplasmic Male Sterility Sources in Broccoli (Brassica Oleracea var. Italica) Using Mitochondrial Markers.

    PubMed

    Shu, Jinshuai; Liu, Yumei; Li, Zhansheng; Zhang, Lili; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

    2016-01-01

    Broccoli (Brassica oleracea var. italica) is an important commercial vegetable crop. As part of an efficient pollination system, cytoplasmic male sterility (CMS) has been widely used for broccoli hybrid production. Identifying the original sources of CMS in broccoli accessions has become an important part of broccoli breeding. In this study, the diversity of the CMS sources of 39 broccoli accessions, including 19 CMS lines and 20 hybrids, were analyzed using mitochondrial markers. All CMS accessions contained the ogu orf138-related DNA fragment and the key genes of nap CMS, pol CMS, and tour CMS were not detected. The 39 CMS accessions were divided into five groups using six orf138-related and two simple sequence repeat markers. We observed that ogu CMS R3 constituted 79.49% of the CMS sources. CMS6 and CMS26 were differentiated from the other accessions using a specific primer. CMS32 was distinguished from the other accessions based on a 78-nucleotide deletion at the same locus as the orf138-related sequence. When the coefficient was about 0.90, five CMS accessions (13CMS6, 13CMS23, 13CMS24, 13CMS37, and 13CMS39) exhibiting abnormal floral organs with poor seed setting were grouped together. The polymerase chain reaction amplification profiles for these five accessions differed from those of the other accessions. We identified eight useful molecular markers that can be used to detect CMS types during broccoli breeding. Our data also provide important information relevant to future studies on the possible origins and molecular mechanisms of CMS in broccoli.

  16. Detection of the Diversity of Cytoplasmic Male Sterility Sources in Broccoli (Brassica Oleracea var. Italica) Using Mitochondrial Markers

    PubMed Central

    Shu, Jinshuai; Liu, Yumei; Li, Zhansheng; Zhang, Lili; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

    2016-01-01

    Broccoli (Brassica oleracea var. italica) is an important commercial vegetable crop. As part of an efficient pollination system, cytoplasmic male sterility (CMS) has been widely used for broccoli hybrid production. Identifying the original sources of CMS in broccoli accessions has become an important part of broccoli breeding. In this study, the diversity of the CMS sources of 39 broccoli accessions, including 19 CMS lines and 20 hybrids, were analyzed using mitochondrial markers. All CMS accessions contained the ogu orf138-related DNA fragment and the key genes of nap CMS, pol CMS, and tour CMS were not detected. The 39 CMS accessions were divided into five groups using six orf138-related and two simple sequence repeat markers. We observed that ogu CMS R3 constituted 79.49% of the CMS sources. CMS6 and CMS26 were differentiated from the other accessions using a specific primer. CMS32 was distinguished from the other accessions based on a 78-nucleotide deletion at the same locus as the orf138-related sequence. When the coefficient was about 0.90, five CMS accessions (13CMS6, 13CMS23, 13CMS24, 13CMS37, and 13CMS39) exhibiting abnormal floral organs with poor seed setting were grouped together. The polymerase chain reaction amplification profiles for these five accessions differed from those of the other accessions. We identified eight useful molecular markers that can be used to detect CMS types during broccoli breeding. Our data also provide important information relevant to future studies on the possible origins and molecular mechanisms of CMS in broccoli. PMID:27446156

  17. Research approach and first results on agglomerate compaction in protoplanetary dust simulation in the Cloud Manipulation System

    NASA Astrophysics Data System (ADS)

    Vedernikov, Andrei; Blum, Jurgen; Ingo Von Borstel, Olaf; Schraepler, Rainer; Balapanov, Daniyar; Cecere, Anselmo

    2016-07-01

    Nanometre and micrometre-sized solid particles are ubiquitous in space and on Earth - from galaxies, interstellar space, protoplanetary and debris disks to planetary rings and atmospheres, planetary surfaces, comets, interplanetary space, Earth's atmosphere. Apparently, the most intriguing problem in the picture of the formation of planets is the transition from individual microscopic dust grains to kilometre-sized planetesimals. Revealing the mechanisms of this transition is one of the main tasks of the European Space Agency's project Interaction in Cosmic and Atmospheric Particle Systems (ICAPS). It was found that Brownian motion driven agglomeration could not provide the transition within reasonable time scale. As a result, at this stage top scientific goals shifted towards forced agglomeration and concentration of particles, targeting revealing the onset of compaction, experimental study of the evolution of fractal dimensions, size and mass distribution, occurrence of bouncing. The main tasks comprise 1) development of the rapid agglomeration model 2) development of the experimental facilities creating big fractal-type agglomerates from 10 to 1000 μm from a cloud of micrometre-size grains; 3) experimental realization of the rapid agglomeration in microgravity and ground conditions; and 4) in situ investigation of the morphology, mobility, mechanical and optical properties of the free-floating agglomerates, including investigation of thermophoresis, photophoresis of the agglomerates and of the two-phase flow phenomena. To solve the experimental part of the tasks we developed a Cloud Manipulation System, realized as a breadboard (CMS BB) for long duration microgravity platforms and a simplified laboratory version (CMS LV) mostly oriented on short duration microgravity and ground tests. The new system is based on the use of thermophoresis, most favourable for cloud manipulation without creating additional particle-particle forces in the cloud with a possibility of growing single agglomerate out of the whole cloud. The cloud manipulation system additionally provides temperature stabilization or, on the contrary, high temperature variation in the observation volume; formation of controlled temperature gradients, intensive three-dimensional periodic shear flow or three-dimensional gas density pulsations of the contraction-expansion type; application of electrostatic gradients including electro dynamic balancing; imposing of photophoretic force, etc. Their choice and/or combination depend upon particular experimental task. Experiments on forced agglomeration in short duration microgravity conditions of the Bremen drop tower succeeded in rapid growth of extended agglomerates, formation of complex three-dimensional cloud patterns, allowed observing controlled cloud displacement, cloud trapping, particle separation with respect to their electrical charge. The breadboard (CMS BB) and the laboratory version of the Cloud Manipulation System (CMS LV) are new types of scientific instrument with high scientific potential. ESA PRODEX program, the Belgian Federal Science Policy Office, DLR project 50WM1223, ZARM Drop Tower Operation and Service Company Ltd. are greatly acknowledged.

  18. Effects of lifestyle intervention using patient-centered cognitive behavioral therapy among patients with cardio-metabolic syndrome: a randomized, controlled trial.

    PubMed

    Zhang, Ying; Mei, Songli; Yang, Rui; Chen, Ling; Gao, Hang; Li, Li

    2016-11-18

    Cardio-metabolic syndrome (CMS) is a highly prevalent condition. There is an urgent need to identify effective and integrated multi-disciplinary approaches that can reduce risk factors for CMS. Sixty-two patients with a history of CMS were randomized 1:1 into two groups: a standard information -only group (control), or a self-regulated lifestyle waist circumference (patient-centered cognitive behavioral therapy) intervention group. A pretest and posttest, controlled, experimental design was used. Outcomes were measured at the baseline (week 0) and at the end of intervention (week 12). Comparisons were drawn between groups and over time. The mean (standard deviation) age of the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the participants were female. Both groups showed no significant differences in Demographic variables and the metabolic syndrome indicators at baseline. While the control group only showed modest improvement after 12 weeks, compared to baseline, the intervention group demonstrated significant improvement from baseline. This study controlled for patients' demographics and baseline characteristics when assessing the effects of intervention. After adjusting for age, education and baseline level, the experimental group and the control group were statistically significant different in the following post-treatment outcomes: WC (F = 35.96, P < 0.001), TG (F = 18.93, P < 0.001), RSBP (F = 33.89, P < 0.001) and SF-36(F = 157.93, P < 0.001). The results showed patients' age and education were not strong predictors of patients' outcome (including WC, TG, RSBP and SF-36). Lifestyle intervention on patient-centered cognitive behavioral therapy can improve the physical and mental health conditions among individuals reporting a history of cardio-metabolic syndrome, and possibly provided preliminary benefits for the treatment of CMS. Chinese Clinical Trial Register #, ChiCTR15006148 .

  19. [Association between the office, visit-to-visit and 24-hour ambulatory systolic blood pressure and vascular damages in the elderly].

    PubMed

    Zheng, X M; Li, C H; Wu, Y T; Zhao, H Y; Jin, C; Song, L; Zhao, H L; Liu, J; Zhang, R Y; Li, W; Chen, S H; Wu, S L

    2016-07-24

    To investigate the association between different kinds of systolic blood pressure (SBP, including office, visit-to-visit, 24-hour ambulatory) and vascular damages (represented by carotid intima-media thickness, CIMT; brachial-ankle pulse wave velocity, baPWV) in the elderly. A total of 2 814 participants aged of ≥60 years old and retired employees were selected with random sampling method from the individuals who took part in 2006-2007, 2008-2009, 2010-2011 health examination in Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital and with 24-hour ambulatory blood pressure monitoring data, CIMT and baPWV.Finally, 2 146 participants (1 438 males, average age (67.3±6.0) years old) were included to the analysis.Multivariable regression analysis was used to analyze association between the office, visit-to-visit, 24-hour, day-time, night-time SBP and CIMT and baPWV, respectively. (1) The average SBP, DBP, CIMT and baPWV were (137.0±20.4) mmHg(1 mmHg=0.133 kPa), (83.5±11.0) mmHg, (0.92±0.18)mm and (1 781.7±353.2)cm/s.(2) The participants were divided into high and low level groups according to the median of different SBPs, respectively.The results indicated that CIMT and baPWV were significantly higher in high level groups than in low level groups (all P<0.01). (3) After adjusting for gender and age, the partial correlate analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP positively associated with CIMT and baPWV (all P<0.01). (4) After adjusting for confounding factors, multivariable regression analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP were positively and linearly associated with CIMT and baPWV in total cohort, and standard regression coefficients were 0.157, 0.208, 0.175, 0.169, 0.163, 0.479, 0.420, 0.401, 0.389 and 0.354, respectively.In addition, similar results were observed in male and female participants but there was no significance between night-time SBP and CIMT in female participants. Office, visit-to-visit, 24-hour, day-time, night-time SBP are associated with vascular damages, and the best associations are observed between visit-to-visit SBP and vascular function damage. Chinese CLINICAL TRIAL REGISTRY, ChiCTR-TNC-1100 1489.

  20. Comparative Gene Expression Analyses Reveal Distinct Molecular Signatures between Differentially Reprogrammed Cardiomyocytes.

    PubMed

    Zhou, Yang; Wang, Li; Liu, Ziqing; Alimohamadi, Sahar; Yin, Chaoying; Liu, Jiandong; Qian, Li

    2017-09-26

    Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes [iCMs]) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CMs and iCMs are still unknown. Here, we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status, whereas iCMs exhibit a maturation status that more closely resembles that of adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis, whereas iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell-cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. 45 CFR 150.203 - Circumstances requiring CMS enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Circumstances requiring CMS enforcement. 150.203... CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for... requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS) in...

  2. The CMS muon system: status and upgrades for LHC Run-2 and performance of muon reconstruction with 13 TeV data

    NASA Astrophysics Data System (ADS)

    Battilana, C.

    2017-01-01

    The CMS muon system has played a key role for many physics results obtained from the LHC Run-1 and Run-2 data. During the Long Shutdown (2013-2014), as well as during the last year-end technical stop (2015-2016), significant consolidation and upgrades have been carried out on the muon detectors and on the L1 muon trigger. The algorithms for muon reconstruction and identification have also been improved for both the High-Level Trigger and the offline reconstruction. Results of the performance of muon detectors, reconstruction and trigger, obtained using data collected at 13 TeV centre-of-mass energy during the 2015 and 2016 LHC runs, will be presented. Comparison of simulation with experimental data will also be discussed where relevant. The system's state of the art performance will be shown, and the improvements foreseen to achieve excellent overall quality of muon reconstruction in CMS, in the conditions expected during the high-luminosity phase of Run-2, will be described.

  3. One Year of FOS Measurements in CMS Experiment at CERN

    NASA Astrophysics Data System (ADS)

    Szillási, Zoltán; Buontempo, Salvatore; Béni, Noémi; Breglio, Giovanni; Cusano, Andrea; Laudati, Armando; Giordano, Michele; Saccomanno, Andrea; Druzhkin, Dmitry; Tsirou, Andromachi

    Results are presented on the activity carried out by our research group, in collaboration with the SME Optosmart s.r.l. (an Italian spin-off company), on the application of Fiber Optic Sensor (FOS) techniques to monitor high-energy physics (HEP) detectors. Assuming that Fiber Bragg Grating sensors (FBGs) radiation hardness has been deeply studied for other field of application, we have applied the FBG technology to the HEP research domain. We present here the experimental evidences of the solid possibility to use such a class of sensors also in HEP detector very complex environmental side conditions. In particular we present more than one year data results of FBG measurements in the Compact Muon Solenoid (CMS) experiment set up at the CERN, where we have monitored temperatures (within CMS core) and strains in different locations by using FBG sensors during the detector operation with the Large Hadron Collider (LHC) collisions and high magnetic field. FOS data and FOS readout system stability and reliability is demonstrated, with continuous 24/24 h 7/7d data taking under severe and complex side conditions.

  4. Testing the 2-TeV resonance with trileptons

    DOE PAGES

    Das, Arindam; Nagata, Natsumi; Okada, Nobuchika

    2016-03-09

    The CMS collaboration has reported a 2.8 excess in the search of the SU(2) R gauge bosons decaying through right-handed neutrinos into the two electron plus two jets (more » $eejj$) final states. This can be explained if the SU(2) Rcharged gauge bosons W$$±\\atop{R}$$ have a mass of around 2TeV and a right-handed neutrino with a mass of O(1)TeV mainly decays to electron. Indeed, recent results in several other experiments, especially that from the ATLAS diboson resonance search, also indicate signatures of such a 2TeV gauge boson. However, a lack of the same-sign electron events in the CMS $eejj$ search challenges the interpretation of the right-handed neutrino as a Majorana fermion. Taking this situation into account, in this paper, we consider a possibility of explaining the CMS eejj excess based on the SU(2) L ⓍSU(2) RⓍ U(1) B-L gauge theory with pseudo-Dirac neutrinos. We fi nd that both the CMS excess events and the ATLAS diboson anomaly can actually be explained in this framework without conflicting with the current experimental bounds. This setup in general allows sizable left-right mixing in both the charged gauge boson and neutrino sectors, which enables us to probe this model through the trilepton plus missing energy search at the LHC. It turns out that the number of events in this channel predicted in our model is in good agreement with that observed by the CMS collaboration. We also discuss prospects for testing this model at the LHC Run-II experiments.« less

  5. CMS: A Web-Based System for Visualization and Analysis of Genome-Wide Methylation Data of Human Cancers

    PubMed Central

    Huang, Yi-Wen; Roa, Juan C.; Goodfellow, Paul J.; Kizer, E. Lynette; Huang, Tim H. M.; Chen, Yidong

    2013-01-01

    Background DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Methodology/Principal Findings Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. Conclusions/Significance CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/. PMID:23630576

  6. CMS: a web-based system for visualization and analysis of genome-wide methylation data of human cancers.

    PubMed

    Gu, Fei; Doderer, Mark S; Huang, Yi-Wen; Roa, Juan C; Goodfellow, Paul J; Kizer, E Lynette; Huang, Tim H M; Chen, Yidong

    2013-01-01

    DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/.

  7. Hydro-metrologic assessment of October 2015 extreme precipitation event on Santee Experimental Forest Watersheds, SC

    Treesearch

    Devendra M. Amatya; Charles A. Harrison; Carl C. Trettin

    2016-01-01

    The extreme precipitation event on October 3-4, 2015, likely resulting from the convergence of a persistent the terrain, and thecirculation associated with Hurricane Joaquin off the eastern Atlantic Coast(http://cms.met.psu.edu/sref/severe/2015/04Oct2015.pdf) resulted...

  8. Emergency Department Crowding and Outcomes After Emergency Department Discharge

    PubMed Central

    Gabayan, Gelareh Z.; Derose, Stephen F.; Chiu, Vicki Y.; Yiu, Sau C.; Sarkisian, Catherine A.; Jones, Jason P.; Sun, Benjamin C.

    2015-01-01

    Study objective We assess whether a panel of emergency department (ED) crowding measures, including 2 reported by the Centers for Medicare & Medicaid Services (CMS), is associated with inpatient admission and death within 7 days of ED discharge. Methods We conducted a retrospective cohort study of ED discharges, using data from an integrated health system for 2008 to 2010. We assessed patient transit-level (n=3) and ED system-level (n=6) measures of crowding, using multivariable logistic regression models. The outcome measures were inpatient admission or death within 7 days of ED discharge. We defined a clinically important association by assessing the relative risk ratio and 95% confidence interval (CI) difference and also compared risks at the 99th percentile and median value of each measure. Results The study cohort contained a total of 625,096 visits to 12 EDs. There were 16,957 (2.7%) admissions and 328 (0.05%) deaths within 7 days. Only 2 measures, both of which were patient transit measures, were associated with the outcome. Compared with a median evaluation time of 2.2 hours, the evaluation time of 10.8 hours (99th percentile) was associated with a relative risk of 3.9 (95% CI 3.7 to 4.1) of an admission. Compared with a median ED length of stay (a CMS measure) of 2.8 hours, the 99th percentile ED length of stay of 11.6 hours was associated with a relative risk of 3.5 (95% CI 3.3 to 3.7) of admission. No system measure of ED crowding was associated with outcomes. Conclusion Our findings suggest that ED length of stay is a proxy for unmeasured differences in case mix and challenge the validity of the CMS metric as a safety measure for discharged patients. PMID:26003004

  9. Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

    PubMed

    Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

    2010-08-01

    The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

  10. Matrigel Mattress: A Method for the Generation of Single Contracting Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Feaster, Tromondae K; Cadar, Adrian G; Wang, Lili; Williams, Charles H; Chun, Young Wook; Hempel, Jonathan E; Bloodworth, Nathaniel; Merryman, W David; Lim, Chee Chew; Wu, Joseph C; Knollmann, Björn C; Hong, Charles C

    2015-12-04

    The lack of measurable single-cell contractility of human-induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) currently limits the utility of hiPSC-CMs for evaluating contractile performance for both basic research and drug discovery. To develop a culture method that rapidly generates contracting single hiPSC-CMs and allows quantification of cell shortening with standard equipment used for studying adult CMs. Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs maintained on a control substrate (<0.1-mm thick 1:60 diluted Matrigel, control hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod-shape morphology and significantly increased sarcomere length. Contractile parameters of mattress hiPSC-CMs measured with video-based edge detection were comparable with those of freshly isolated adult rabbit ventricular CMs. Morphological and contractile properties of mattress hiPSC-CMs were consistent across cryopreserved hiPSC-CMs generated independently at another institution. Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses to positive inotropic agents, such as myofilament calcium sensitizers. Mattress hiPSC-CMs exhibit molecular changes that include increased expression of the maturation marker cardiac troponin I and significantly increased action potential upstroke velocity because of a 2-fold increase in sodium current (INa). The Matrigel mattress method enables the rapid generation of robustly contracting hiPSC-CMs and enhances maturation. This new method allows quantification of contractile performance at the single-cell level, which should be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity testing. © 2015 American Heart Association, Inc.

  11. Vascular Endothelial Growth Factor Secretion by Nonmyocytes Modulates Connexin-43 Levels in Cardiac Organoids

    PubMed Central

    Iyer, Rohin K.; Odedra, Devang; Chiu, Loraine L.Y.; Vunjak-Novakovic, Gordana

    2012-01-01

    We previously showed that the sequential, but not simultaneous, culture of endothelial cells (ECs), fibroblasts (FBs), and cardiomyocytes (CMs) resulted in elongated, beating cardiac organoids. We hypothesized that the expression of Cx43 and contractile function are mediated by vascular endothelial growth factor (VEGF) released by nonmyocytes during the preculture period. Cardiac organoids (∼200 μm diameter) were cultivated in microchannels to enable rapid screening. Three experimental groups were formed: (i) Simultaneous Preculture (ECs+FBs for 48 h, followed by CMs), (ii) Sequential Preculture (ECs for 24 h, FBs for 24 h, followed by CMs), and (iii) Simultaneous Triculture (ECs+FBs+CMs). Controls included CMs only, FBs only, and ECs only groups, and preculture with ECs only or FBs only. The highest VEGF levels were found in the Preculture groups [Simultaneous Preculture, 8.9±2.7 ng/(mL·h−1); Sequential Preculture, 16.6±3.4 ng/(mL·h−1)], as compared with Simultaneous Triculture where VEGF was not detectable, as shown by enzyme-linked immunosorbent assay. Analytical flow cytometry showed that VEGFR2 was expressed by ECs (86%±2 VEGFR2+), FBs (44%±1 VEGFR2+), and CMs (49%±2 VEGFR2+), showing that all three cell types were capable of responding to changes in VEGF. Addition of anti-VEGF neutralizing IgG (0.4 μg/mL) to Simultaneous Preculture resulted in 3-fold decrease in Cx43 mRNA and 1.5-fold decrease in Cx43 protein, while Simultaneous Triculture supplemented with VEGF ligand (30 ng/mL) had a threefold increase in Cx43 mRNA and a twofold increase in Cx43 protein. Addition of a small molecule inhibitor of the VEGFR2 receptor (19.4 nM) to Sequential Preculture caused a 1.4-fold decrease in Cx43 mRNA and a 4.1-fold decrease in Cx43 protein. Cx43 was localized within CMs, and not within FBs or ECs. Enriched CM organoids and Sequential Preculture organoids grown in the presence of VEGFR2 inhibitor displayed low levels of Cx43 and poor functional properties. Taken together, these results suggest that endogenous VEGF-VEGFR2 signaling enhanced Cx43 expression and cardiac function in engineered cardiac organoids. PMID:22519405

  12. 77 FR 31618 - Medicaid Program; Announcement of Requirements and Registration for CMS Provider Screening...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services (CMS) [CMS-2382-N... Challenge AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice. SUMMARY: The Centers for Medicare & Medicaid Services (CMS), is announcing the launch of the ``CMS Provider Screening...

  13. CS2 analysis in presence of non-Gaussian background noise - Effect on traditional estimators and resilience of log-envelope indicators

    NASA Astrophysics Data System (ADS)

    Borghesani, P.; Antoni, J.

    2017-06-01

    Second-order cyclostationary (CS2) analysis has become popular in the field of machine diagnostics and a series of digital signal processing techniques have been developed to extract CS2 components from the background noise. Among those techniques, squared envelope spectrum (SES) and cyclic modulation spectrum (CMS) have gained popularity thanks to their high computational efficiency and simple implementation. The effectiveness of CMS and SES has been previously quantified based on the hypothesis of Gaussian background noise and has led to statistical tests for the presence of CS2 peaks in squared envelope spectra and cyclic modulation spectra. However a recently established link of CMS with SES and of SES with kurtosis has exposed a potential weakness of those indicators in the case of highly leptokurtic background noise. This case is often present in practice when the machine is subjected to highly impulsive phenomena, either due to harsh operating conditions or to electric noise generated by power electronics and captured by the sensor. This study investigates and quantifies for the first time the effect of leptokurtic noise on the capabilities of SES and CMS, by analysing three progressively harsh situations: high kurtosis, infinite kurtosis and alpha-stable background noise (for which even first and second-order moments are not defined). Then the resilience of a recently proposed family of CS2 indicators, based on the log-envelope, is verified analytically, numerically and experimentally in the case of highly leptokurtic noise.

  14. Effects of functional feeds on the lipid composition, transcriptomic responses and pathology in heart of Atlantic salmon (Salmo salar L.) before and after experimental challenge with Piscine Myocarditis Virus (PMCV).

    PubMed

    Martinez-Rubio, Laura; Evensen, Øystein; Krasnov, Aleksei; Jørgensen, Sven Martin; Wadsworth, Simon; Ruohonen, Kari; Vecino, Jose L G; Tocher, Douglas R

    2014-06-11

    Cardiomyopathy syndrome (CMS) is a severe cardiac disease of Atlantic salmon (Salmo salar) recently associated with a double-stranded RNA virus, Piscine Myocarditis Virus (PMCV). The disease has been diagnosed in 75-85 farms in Norway each year over the last decade resulting in annual economic losses estimated at up to €9 million. Recently, we demonstrated that functional feeds led to a milder inflammatory response and reduced severity of heart lesions in salmon experimentally infected with Atlantic salmon reovirus, the causal agent of heart and skeletal muscle inflammation (HSMI). In the present study we employed a similar strategy to investigate the effects of functional feeds, with reduced lipid content and increased eicosapentaenoic acid levels, in controlling CMS in salmon after experimental infection with PMCV. Hepatic steatosis associated with CMS was significantly reduced over the time course of the infection in fish fed the functional feeds. Significant differences in immune and inflammatory responses and pathology in heart tissue were found in fish fed the different dietary treatments over the course of the infection. Specifically, fish fed the functional feeds showed a milder and delayed inflammatory response and, consequently, less severity of heart lesions at earlier and later stages after infection with PMCV. Decreasing levels of phosphatidylinositol in cell membranes combined with the increased expression of genes related with T-cell signalling pathways revealed new interactions between dietary lipid composition and the immune response in fish during viral infection. Dietary histidine supplementation did not significantly affect immune responses or levels of heart lesions. Combined with the previous findings on HSMI, the results of the present study highlight the potential role of clinical nutrition in controlling inflammatory diseases in Atlantic salmon. In particular, dietary lipid content and fatty acid composition may have important immune-modulatory effects in Atlantic salmon that could be potentially beneficial in fish balancing the immune and tissue responses to viral infections.

  15. Combining data from high-energy pp-reactions and neutrinoless double-beta decay: Limits on the mass of the right-handed boson

    NASA Astrophysics Data System (ADS)

    Civitarese, Osvaldo; Suhonen, Jouni; Zuber, Kai

    2016-10-01

    From the recently established lower-limits on the nonobservability of the neutrinoless double-beta decay of 76Ge (GERDA collaboration) and 136Xe (EXO-200 and KamLAND-Zen collaborations), combined with the ATLAS and CMS data, we extract limits for the left-right (LR) mixing angle, ζ, of the SU(2)L ×SU(2)R electroweak Hamiltonian. For the theoretical analysis, which is a model dependent, we have adopted a minimal extension of the Standard Model (SM) of Electroweak Interactions belonging to the SU(2)L ×SU(2)R representation. The nuclear-structure input of the analysis consists of a set of matrix elements and phase-space factors, and the experimental lower-limits for the half-lives. The other input are the ATLAS and CMS cross-section measurements of the pp-collisions into two-jets and two-leptons, performed at the large hadron collider (LHC). Our analysis yields the limit ζ < 10-3 for MR > 3TeV, by combining the model-dependent limits extracted from the double-beta-decay measurements and those extracted from the results of the CMS and ATLAS measurements.

  16. Study of inclusive single-jet production in the framework of kt-factorization unintegrated parton distributions

    NASA Astrophysics Data System (ADS)

    Aminzadeh Nik, R.; Modarres, M.; Masouminia, M. R.

    2018-05-01

    The present work is intended to study the double-differential cross section of the inclusive single-jet production as the functions of the transverse momentum and the rapidity of the jet in the high-energy hadron-hadron collisions. The angular-ordering-constraint kt-factorization framework is used to calculate the above cross section that is available experimentally. The conditions are taken in accordance with the LHC experiments. The results are compared and analyzed using the existing CMS LHC data. The scheme-dependent unintegrated parton distribution functions (UPDF) of Kimber-Martin-Ryskin (KMR) and Martin-Ryskin-Watt (MRW) in the leading-order and the next-to-leading order (NLO) are used to predict the input partonic UPDF. The utilized phenomenological frameworks prove to be relatively successful in generating satisfactory results compared to the different experiment data, such as CMS (8 and 13 TeV). Extensive discussions and comparisons are made regarding the behavior of the contributing partonic subprocesses. Finally, it is shown that the application of the KMR UPDF to the single-jet differential cross sections have better agreement with the CMS data; on the other hand, they are very similar to those of NLO-MRW.

  17. Effect of ultrasonic stimulation on particle transport and fate over different lengths of porous media

    NASA Astrophysics Data System (ADS)

    Chen, Xingxin; Wu, Zhonghan; Cai, Qipeng; Cao, Wei

    2018-04-01

    It is well established that seismic waves traveling through porous media stimulate fluid flow and accelerate particle transport. However, the mechanism remains poorly understood. To quantify the coupling effect of hydrodynamic force, transportation distance, and ultrasonic stimulation on particle transport and fate in porous media, laboratory experiments were conducted using custom-built ultrasonic-controlled soil column equipment. Three column lengths (23 cm, 33 cm, and 43 cm) were selected to examine the influence of transportation distance. Transport experiments were performed with 0 W, 600 W, 1000 W, 1400 W, and 1800 W of applied ultrasound, and flow rates of 0.065 cm/s, 0.130 cm/s, and 0.195 cm/s, to establish the roles of ultrasonic stimulation and hydrodynamic force. The laboratory results suggest that whilst ultrasonic stimulation does inhibit suspended-particle deposition and accelerate deposited-particle release, both hydrodynamic force and transportation distance are the principal controlling factors. The median particle diameter for the peak concentration was approximately 50% of that retained in the soil column. Simulated particle-breakthrough curves using extended traditional filtration theory effectively described the experimental curves, particularly the curves that exhibited a higher tailing concentration.

  18. 42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

  19. 42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

  20. 42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

  1. 42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

  2. 42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

  3. Experimental High Energy Physics Research

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

    Hohlmann, Marcus

    This final report summarizes activities of the Florida Tech High Energy Physics group supported by DOE under grant #DE-SC0008024 during the period June 2012 – March 2015. We focused on one of the main HEP research thrusts at the Energy Frontier by participating in the CMS experiment. We were exploiting the tremendous physics opportunities at the Large Hadron Collider (LHC) and prepared for physics at its planned extension, the High-Luminosity LHC. The effort comprised a physics component with analysis of data from the first LHC run and contributions to the CMS Phase-2 upgrades in the muon endcap system (EMU) formore » the High-Luminosity LHC. The emphasis of our hardware work was the development of large-area Gas Electron Multipliers (GEMs) for the CMS forward muon upgrade. We built a production and testing site for such detectors at Florida Tech to complement future chamber production at CERN. The first full-scale CMS GE1/1 chamber prototype ever built outside of CERN was constructed at Florida Tech in summer 2013. We conducted two beam tests with GEM prototype chambers at CERN in 2012 and at FNAL in 2013 and reported the results at conferences and in publications. Principal Investigator Hohlmann served as chair of the collaboration board of the CMS GEM collaboration and as co-coordinator of the GEM detector working group. He edited and authored sections of the detector chapter of the Technical Design Report (TDR) for the GEM muon upgrade, which was approved by the LHCC and the CERN Research Board in 2015. During the course of the TDR approval process, the GEM project was also established as an official subsystem of the muon system by the CMS muon institution board. On the physics side, graduate student Kalakhety performed a Z' search in the dimuon channel with the 2011 and 2012 CMS datasets that utilized 20.6 fb⁻¹ of p-p collisions at √s = 8 TeV. For the dimuon channel alone, the 95% CL lower limits obtained on the mass of a Z' resonance are 2770 GeV for a Z' with the same standard-model couplings as the Z boson. Our student team operated a Tier-3 cluster on the Open Science Grid (OSG) to support local CMS physics analysis and remote OSG activity. As a service to the HEP community, Hohlmann participated in the Snowmass effort over the course of 2013. Specifically, he acted as a liaison for gaseous detectors between the Instrumentation Frontier and the Energy Frontier and contributed to five papers and reports submitted to the summer study.« less

  4. Eliminating Health Disparities through Action on the Social Determinants of Health: A Systematic Review of Home Visiting in the United States, 2005-2015.

    PubMed

    Abbott, Laurie S; Elliott, Lynn T

    2017-01-01

    The purpose of this systematic literature review was to synthesize the results of transdisciplinary interventions designed with a home visit component in experimental and quasi-experimental studies having representative samples of racial and ethnic minorities. The design of this systematic review was adapted to include both experimental and quasi-experimental quantitative studies. The predetermined inclusion criteria were studies (a) having an experimental or quasi-experimental quantitative design, (b) having a home visit as a research component, (c) including a prevention research intervention strategy targeting health and/or safety issues, (d) conducted in the United States, (e) having representation (at least 30% in the total sample size) of one or more racial/ethnic minority, (f) available in full text, and (g) published in a peer-reviewed journal between January, 2005 and December, 2015. Thirty-nine articles were included in the review. There were 20 primary prevention, 5 secondary prevention, and 14 tertiary prevention intervention studies. Community and home visitation interventions by nurses can provide an effective means for mitigating social determinants of health by empowering people at risk for health disparities to avoid injury, maintain health, and prevent and manage existing disease. © 2016 Wiley Periodicals, Inc.

  5. Effects of intravenous bolus injection of nicorandil on renal artery flow velocity assessed by color Doppler ultrasound.

    PubMed

    Shimamoto, Yukiko; Kubo, Takashi; Tanabe, Kazumi; Emori, Hiroki; Katayama, Yosuke; Nishiguchi, Tsuyoshi; Taruya, Akira; Kameyama, Takeyoshi; Orii, Makoto; Yamano, Takashi; Kuroi, Akio; Yamaguchi, Tomoyuki; Takemoto, Kazushi; Matsuo, Yoshiki; Ino, Yasushi; Tanaka, Atsushi; Hozumi, Takeshi; Terada, Masaki; Akasaka, Takashi

    2017-01-01

    Previous animal studies have shown that a potassium channel opener, nicorandil, provokes vasodilation in renal microvasculature and increases renal blood flow. We conducted a clinical study that aimed to evaluate the effect of nicorandil on renal artery blood flow in comparison with nitroglycerin by using color Doppler ultrasound. The present study enrolled 40 patients with stable coronary artery disease who had no renal arterial stenosis and renal parenchymal disease. The patients received intravenous administration of nicorandil (n=20) or nitroglycerin (n=20). Before and after the administration, renal artery blood flow velocity was measured by color-guided pulsed-wave Doppler. The peak-systolic, end-diastolic, and mean renal artery blood flow velocities before the administration were not different between the nicorandil group and the nitroglycerin group. The peak-systolic (79±15cm/s to 99±21cm/s, p<0.001; and 78±19cm/s to 85±19cm/s, p=0.004), end-diastolic (22±5cm/s to 28±8cm/s, p<0.001; and 24±6cm/s to 26±6cm/s, p=0.005) and mean (41±6cm/s to 49±9cm/s, p<0.001; and 43±9cm/s to 45±9cm/s, p=0.009) renal artery flow velocities increased significantly in either group. The nominal changes in the peak-systolic (20±10cm/s vs. 7±8cm/s, p<0.001), end-diastolic (5±4cm/s vs. 2±3cm/s, p=0.001), and mean (8±5cm/s vs. 2±2cm/s, p<0.001) renal artery blood flow velocities were significantly greater in the nicorandil group compared with the nitroglycerin group. Intravenous nicorandil increased renal artery blood flow velocity in comparison with nitroglycerin. Nicorandil has a significant effect on renal hemodynamics. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  6. Altered iPSC-derived neurons’ sodium channel properties in subjects with Monge's disease

    PubMed Central

    Zhao, Huiwen W.; Gu, Xiang Q.; Chailangkarn, Thanathom; Perkins, Guy; Callacondo, David; Appenzeller, Otto; Poulsen, Orit; Zhou, Dan; Muotri, Alysson R.; Haddad, Gabriel G.

    2015-01-01

    Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at a high altitude (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at the high altitude; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed fibroblast cells from both CMS and non-CMS subjects’ skin biopsies into the induced pluripotent stem cells (iPSCs), then differentiated into neurons and compared their neuronal properties. We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na+ channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS. PMID:25559931

  7. The influence of a mental health home visit service partnership intervention on the caregivers' home visit service satisfaction and care burden.

    PubMed

    Cheng, Jui-Fen; Huang, Xuan-Yi; Lin, Mei-Jue; Wang, Ya-Hui; Yeh, Tzu-Pei

    2018-02-01

    To investigate a community-based and hospital-based home visit partnership intervention in improving caregivers' satisfaction with home service and reducing caregiver burden. The community-oriented mental healthcare model prevails internationally. After patients return to the community, family caregivers are the patients' main support system and they also take the most of the burden of caring for patients. It is important to assist these caregivers by building good community healthcare models. A longitudinal quasi-experimental quantitative design. The experimental group (n = 109) involved "partnership" intervention, and the control group (n = 101) maintained routine home visits. The results were measured before the intervention, 6 and 12 months after the partnership intervention. Six months after the partnership intervention, the satisfaction of the experimental group was higher than the control group for several aspects of care. Although the care burden was reduced in the experimental group, there was no significant difference between the two groups. This study confirms that the partnership intervention can significantly improve caregiver satisfaction with home services, without reducing the care burden. The community-based and hospital-based mental health home visit service partnership programme could improve the main caregiver's satisfaction with the mental health home visit services, while the reduction in care burden may need government policies for the provision of more individual and comprehensive assistance. © 2017 John Wiley & Sons Ltd.

  8. Fabrication of fibrillized collagen microspheres with the microstructure resembling an extracellular matrix.

    PubMed

    Matsuhashi, Aki; Nam, Kwangwoo; Kimura, Tsuyoshi; Kishida, Akio

    2015-04-14

    Microspheres using artificial or natural materials have been widely applied in the field of tissue engineering and drug delivery systems. Collagen is being widely used for microspheres because of its abundancy in the extracellular matrix (ECM), and its good biocompatibility. The purpose of this study is to establish the appropriate condition for preparing collagen microspheres (CMS) and fibrillized collagen microspheres (fCMS) using water-in-oil (W/O) emulsion. Collagen can be tailored to mimic the native cell environment possessing a similar microstructure to that of the ECM by conditioning the aqueous solution. We focused on the preparation of stable and injectable CMS and fCMS which is stable and would promote the healing response. Controlling the interfacial properties of hydrophilic-lipophilic balance (HLB), we obtained CMS and fCMS with various sizes and various morphologies. The microsphere prepared with wetting agents showed good microsphere formation, but too low or too high HLB value caused low yield and uncontrollable size distribution. The change in the surfactant amount and the rotor speed also affected the formation of the CMS and fCMS, where the low surfactant amount and fast rotor speed produced smaller CMS and fCMS. In the case of fCMS, the presence of NaCl made it possible to prepare stable fCMS without using any cross-linker due to fibrillogenesis and gelling of collagen molecules. The microstructure of fCMS was similar to that of the native tissue indicating that the fCMS would replicate its function in vivo.

  9. Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database.

    PubMed

    Jacobs, Jeffrey P; Shahian, David M; He, Xia; O'Brien, Sean M; Badhwar, Vinay; Cleveland, Joseph C; Furnary, Anthony P; Magee, Mitchell J; Kurlansky, Paul A; Rankin, J Scott; Welke, Karl F; Filardo, Giovanni; Dokholyan, Rachel S; Peterson, Eric D; Brennan, J Matthew; Han, Jane M; McDonald, Donna; Schmitz, DeLaine; Edwards, Fred H; Prager, Richard L; Grover, Frederick L

    2016-01-01

    The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) has been successfully linked to the Centers for Medicare and Medicaid (CMS) Medicare database, thereby facilitating comparative effectiveness research and providing information about long-term follow-up and cost. The present study uses this link to determine contemporary completeness, penetration, and representativeness of the STS ACSD. Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft (CABG) surgery hospitalizations discharged between 2000 and 2012, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% in 2000 to 90% in 2012. In 2012, 973 of 1,081 CMS CABG sites (90%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% in 2000 to 94% in 2012. In 2012, 71,634 of 76,072 CMS CABG hospitalizations (94%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2012. In 2012, 69,213 of 70,932 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. Linkage of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data facilitates studying long-term outcomes and costs of cardiothoracic surgery. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Enhancing Parent-Child Interaction during Foster Care Visits: Experimental Assessment of an Intervention

    ERIC Educational Resources Information Center

    Haight, Wendy L.; Mangelsdorf, Sarah; Black, James; Szewczyk, Margaret; Schoppe, Sarah; Giorgio, Grace; Madrigal, Karen; Tata, Lakshmi

    2005-01-01

    Mothers of young children recently placed in foster care participated in an intervention to enhance parent-child interaction during visits. The mothers all reported substantial loss and trauma histories. Immediately prior to the visits, the mothers were coached on strategies for separating from their children at the visit's end. The mothers…

  11. Correlation between human ether‐a‐go‐go‐related gene channel inhibition and action potential prolongation

    PubMed Central

    Saxena, P; Hortigon‐Vinagre, M P; Beyl, S; Baburin, I; Andranovits, S; Iqbal, S M; Costa, A; IJzerman, A P; Kügler, P; Timin, E

    2017-01-01

    Background and Purpose Human ether‐a‐go‐go‐related gene (hERG; Kv11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro‐arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs). The interference from accompanying block of Cav1.2 and Nav1.5 channels was investigated along with an in silico AP model. Experimental Approach Drug‐induced changes in APD were assessed in hiPSC‐CMs using voltage‐sensitive dyes. The IC50 values for dofetilide and 13 derivatives on hERG current were estimated in an HEK293 expression system. The relative potency of each drug on APD was estimated by calculating the dose (D150) required to prolong the APD at 90% (APD90) repolarization by 50%. Key Results The D150 in hiPSC‐CMs was linearly correlated with IC50 of hERG current. In silico simulations supported this finding. Three derivatives inhibited hERG without prolonging APD, and these compounds also inhibited Cav1.2 and/or Nav1.5 in a channel state‐dependent manner. Adding Cav1.2 and Nav1.2 block to the in silico model recapitulated the direction but not the extent of the APD change. Conclusions and Implications Potency of hERG current inhibition correlates linearly with an index of APD in hiPSC‐CMs. The compounds that do not correlate have additional effects including concomitant block of Cav1.2 and/or Nav1.5 channels. In silico simulations of hiPSC‐CMs APs confirm the principle of the multiple ion channel effects. PMID:28681507

  12. CMS Analysis and Data Reduction with Apache Spark

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

    Gutsche, Oliver; Canali, Luca; Cremer, Illia

    Experimental Particle Physics has been at the forefront of analyzing the world's largest datasets for decades. The HEP community was among the first to develop suitable software and computing tools for this task. In recent times, new toolkits and systems for distributed data processing, collectively called "Big Data" technologies have emerged from industry and open source projects to support the analysis of Petabyte and Exabyte datasets in industry. While the principles of data analysis in HEP have not changed (filtering and transforming experiment-specific data formats), these new technologies use different approaches and tools, promising a fresh look at analysis ofmore » very large datasets that could potentially reduce the time-to-physics with increased interactivity. Moreover these new tools are typically actively developed by large communities, often profiting of industry resources, and under open source licensing. These factors result in a boost for adoption and maturity of the tools and for the communities supporting them, at the same time helping in reducing the cost of ownership for the end-users. In this talk, we are presenting studies of using Apache Spark for end user data analysis. We are studying the HEP analysis workflow separated into two thrusts: the reduction of centrally produced experiment datasets and the end-analysis up to the publication plot. Studying the first thrust, CMS is working together with CERN openlab and Intel on the CMS Big Data Reduction Facility. The goal is to reduce 1 PB of official CMS data to 1 TB of ntuple output for analysis. We are presenting the progress of this 2-year project with first results of scaling up Spark-based HEP analysis. Studying the second thrust, we are presenting studies on using Apache Spark for a CMS Dark Matter physics search, comparing Spark's feasibility, usability and performance to the ROOT-based analysis.« less

  13. 78 FR 38986 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... that information was collected under Part B. The QIMS Account Registration and the ESRD Application..., CMS-1728-94, CMS-10174, CMS-10305 and CMS-10488] Agency Information Collection Activities: Proposed... comment on CMS' intention to collect information from the public. Under the Paperwork Reduction Act of...

  14. 42 CFR 482.74 - Condition of participation: Notification to CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Notification to CMS... participation: Notification to CMS. (a) A transplant center must notify CMS immediately of any significant... conditions of participation. Instances in which CMS should receive information for follow up, as appropriate...

  15. Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice.

    PubMed

    Braun, Lesley A; Tiralongo, Evelin; Wilkinson, Jenny M; Spitzer, Ondine; Bailey, Michael; Poole, Susan; Dooley, Michael

    2010-07-20

    Complementary medicines (CMs) are popular amongst Australians and community pharmacy is a major supplier of these products. This study explores pharmacy customer use, attitudes and perceptions of complementary medicines, and their expectations of pharmacists as they relate to these products. Pharmacy customers randomly selected from sixty large and small, metropolitan and rural pharmacies in three Australian states completed an anonymous, self administered questionnaire that had been pre-tested and validated. 1,121 customers participated (response rate 62%). 72% had used CMs within the previous 12 months, 61% used prescription medicines daily and 43% had used both concomitantly. Multivitamins, fish oils, vitamin C, glucosamine and probiotics were the five most popular CMs. 72% of people using CMs rated their products as 'very effective' or 'effective enough'. CMs were as frequently used by customers aged 60 years or older as younger customers (69% vs. 72%) although the pattern of use shifted with older age. Most customers (92%) thought pharmacists should provide safety information about CMs, 90% thought they should routinely check for interactions, 87% thought they should recommend effective CMs, 78% thought CMs should be recorded in customer's medication profile and 58% thought pharmacies stocking CMs should also employ a complementary medicine practitioner. Of those using CMs, 93% thought it important for pharmacists to be knowledgeable about CMs and 48% felt their pharmacist provides useful information about CMs. CMs are widely used by pharmacy customers of all ages who want pharmacists to be more involved in providing advice about these products.

  16. Recombination Events Involving the atp9 Gene Are Associated with Male Sterility of CMS PET2 in Sunflower.

    PubMed

    Reddemann, Antje; Horn, Renate

    2018-03-11

    Cytoplasmic male sterility (CMS) systems represent ideal mutants to study the role of mitochondria in pollen development. In sunflower, CMS PET2 also has the potential to become an alternative CMS source for commercial sunflower hybrid breeding. CMS PET2 originates from an interspecific cross of H. petiolaris and H. annuus as CMS PET1, but results in a different CMS mechanism. Southern analyses revealed differences for atp6 , atp9 and cob between CMS PET2, CMS PET1 and the male-fertile line HA89. A second identical copy of atp6 was present on an additional CMS PET2-specific fragment. In addition, the atp9 gene was duplicated. However, this duplication was followed by an insertion of 271 bp of unknown origin in the 5' coding region of the atp9 gene in CMS PET2, which led to the creation of two unique open reading frames orf288 and orf231 . The first 53 bp of orf288 are identical to the 5' end of atp9 . Orf231 consists apart from the first 3 bp, being part of the 271-bp-insertion, of the last 228 bp of atp9 . These CMS PET2-specific orfs are co-transcribed. All 11 editing sites of the atp9 gene present in orf231 are fully edited. The anther-specific reduction of the co-transcript in fertility-restored hybrids supports the involvement in male-sterility based on CMS PET2.

  17. Adverse systemic arterial function in patients with selenium deficiency.

    PubMed

    Chan, Y-H; Siu, C-W; Yiu, K-H; Chan, H-T; Li, S-W; Tam, S; Cheung, B M; Lau, C-P; Lam, T H; Tse, H-F

    2012-01-01

    Experimental studies have shown that selenium is involved in the synthesis of selenoproteins which might contribute to cardiovascular protection. However, the relationship between selenium deficiency and vascular function in clinical context remains unknown. To investigate for any relationship between selenium deficiency and systemic arterial function in patients with high risk of vascular events. Cross-sectional study. 306 consecutive patients with high risk for cardiovascular events (coronary artery disease 35%, acute/ recurrent ischemic stroke 40%, diabetes mellitus 54%) followed up at internal medicine outpatient clinics. Non-invasive brachial-ankle pulse wave velocity (PWV) was determined using vascular profiling system (VP-2000). Long-term intake of selenium was determined by a validated food frequency questionnaire. Mean daily selenium intake was 59.5 ± 52.1 mcg/day, and mean PWV was 1782.4 ± 418.4 cm/s. Patients with selenium intake <10th percentile had significantly higher PWV as compared to patients with intake ≥ 10th percentile (1968.2 ± 648.9 cm/s versus 1762.2 ± 381.6 cm/s, P=0.010). After adjusting for potential confounders including age, gender, history of hypertension, hyperlipidemia, diabetes and cardiovascular disease, smoking status, use of cardiovascular medications, waist-hip ratio, education/ financial status, physical activity, calorie intake and intake of antioxidant vitamins, deficient selenium intake <10th percentile remained independently predictive of increased PWV by +363.4 cm/s [95% CI: 68.1 to 658.6, P=0.016, relative increase 21%]. Selenium deficiency is associated with adverse arterial function in patients with high risk for vascular events.

  18. Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

    PubMed Central

    Jiang, Bo; Xiong, Zhe; Yang, Jun; Wang, Wei; Wang, Yue; Hu, Zhuang-Li; Wang, Fang; Chen, Jian-Guo

    2012-01-01

    BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis. PMID:22335772

  19. 42 CFR 423.2063 - Applicability of laws, regulations and CMS Rulings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Applicability of laws, regulations and CMS Rulings..., ALJ Hearings, MAC review, and Judicial Review § 423.2063 Applicability of laws, regulations and CMS... on ALJs and the MAC. (b) CMS Rulings are published under the authority of the CMS Administrator...

  20. 42 CFR 426.517 - CMS' statement regarding new evidence.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' statement regarding new evidence. 426.517... DETERMINATIONS Review of an NCD § 426.517 CMS' statement regarding new evidence. (a) CMS may review any new... experts; and (5) Presented during any hearing. (b) CMS may submit a statement regarding whether the new...

  1. 42 CFR 405.1063 - Applicability of laws, regulations and CMS Rulings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Applicability of laws, regulations and CMS Rulings... Medicare Coverage Policies § 405.1063 Applicability of laws, regulations and CMS Rulings. (a) All laws and... the MAC. (b) CMS Rulings are published under the authority of the Administrator, CMS. Consistent with...

  2. How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features.

    PubMed

    Lorenzoni, Paulo José; Scola, Rosana Herminia; Kay, Claudia Suemi Kamoi; Werneck, Lineu Cesar; Horvath, Rita; Lochmüller, Hanns

    2018-06-01

    Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.

  3. A novel photo-grafting of acrylamide onto carboxymethyl starch. 1. Utilization of CMS-g-PAAm in easy care finishing of cotton fabrics.

    PubMed

    El-Sheikh, Manal A

    2016-11-05

    The photosensitized grafting of vinyl monomers onto a range of polymeric substrates has been the subject of particular interest in the recent past. Carboxymethyl starch (CMS)-poly acrylamide (PAAm) graft copolymer (CMS-g-PAAm) with high graft yield was successfully prepared by grafting of acrylamide onto CMS using UV irradiation in the presence of the water soluble 4-(trimethyl ammoniummethyl) benzophenone chloride photoinitiator. CMS-g-PAAm with nitrogen content of 8.3% and grafting efficiency up to 98.9% was obtained using 100% AAm, a material: liquor ratio of 1:14 and 1% photinitiator at 30°C for 1h of UV irradiation. The synthesis of CMS-g-PAAm was confirmed by FTIR and Nitrogen content (%). Surface morphology of CMS and surface morphological changes of CMS after grafting with AAm were studied using SEM. Thermal properties of both CMS and CMS-g-PAAm were studied using TGA and DSC. To impart easy care finishing to cotton fabrics, aqueous formulations of: CMS-g-PAAm, dimethylol dihydroxy ethylene urea (DMDHEU), CMS-g-PAAm-DMDHEU mixture or methylolated CMS-g-PAAm were used. Cotton fabrics were padded in these formulations, squeezed to a wet pick up 100%, dried at 100°C for 5min, cured at 150°C for 5min, washed at 50°C for 10min and air-dried. CRA (crease recovery angle) of untreated fabrics and fabrics finished with a mixture of 2% CMS-g-PAAm and 10% DMDHEU or methylolated CMS-g-PAAm (10% formaldehyde) were: 136°, 190°, 288° respectively. Increasing the number of washing cycles up to five cycles results in an insignificant decrease in the CRA and a significant decrease in RF (releasable formaldehyde) of finished fabric samples. The morphologies of the finished and unfinished cotton fabrics were performed by SEM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice

    PubMed Central

    2010-01-01

    Background Complementary medicines (CMs) are popular amongst Australians and community pharmacy is a major supplier of these products. This study explores pharmacy customer use, attitudes and perceptions of complementary medicines, and their expectations of pharmacists as they relate to these products. Methods Pharmacy customers randomly selected from sixty large and small, metropolitan and rural pharmacies in three Australian states completed an anonymous, self administered questionnaire that had been pre-tested and validated. Results 1,121 customers participated (response rate 62%). 72% had used CMs within the previous 12 months, 61% used prescription medicines daily and 43% had used both concomitantly. Multivitamins, fish oils, vitamin C, glucosamine and probiotics were the five most popular CMs. 72% of people using CMs rated their products as 'very effective' or 'effective enough'. CMs were as frequently used by customers aged 60 years or older as younger customers (69% vs. 72%) although the pattern of use shifted with older age. Most customers (92%) thought pharmacists should provide safety information about CMs, 90% thought they should routinely check for interactions, 87% thought they should recommend effective CMs, 78% thought CMs should be recorded in customer's medication profile and 58% thought pharmacies stocking CMs should also employ a complementary medicine practitioner. Of those using CMs, 93% thought it important for pharmacists to be knowledgeable about CMs and 48% felt their pharmacist provides useful information about CMs. Conclusions CMs are widely used by pharmacy customers of all ages who want pharmacists to be more involved in providing advice about these products. PMID:20646290

  5. Recombination Events Involving the atp9 Gene Are Associated with Male Sterility of CMS PET2 in Sunflower

    PubMed Central

    Reddemann, Antje; Horn, Renate

    2018-01-01

    Cytoplasmic male sterility (CMS) systems represent ideal mutants to study the role of mitochondria in pollen development. In sunflower, CMS PET2 also has the potential to become an alternative CMS source for commercial sunflower hybrid breeding. CMS PET2 originates from an interspecific cross of H. petiolaris and H. annuus as CMS PET1, but results in a different CMS mechanism. Southern analyses revealed differences for atp6, atp9 and cob between CMS PET2, CMS PET1 and the male-fertile line HA89. A second identical copy of atp6 was present on an additional CMS PET2-specific fragment. In addition, the atp9 gene was duplicated. However, this duplication was followed by an insertion of 271 bp of unknown origin in the 5′ coding region of the atp9 gene in CMS PET2, which led to the creation of two unique open reading frames orf288 and orf231. The first 53 bp of orf288 are identical to the 5′ end of atp9. Orf231 consists apart from the first 3 bp, being part of the 271-bp-insertion, of the last 228 bp of atp9. These CMS PET2-specific orfs are co-transcribed. All 11 editing sites of the atp9 gene present in orf231 are fully edited. The anther-specific reduction of the co-transcript in fertility-restored hybrids supports the involvement in male-sterility based on CMS PET2. PMID:29534485

  6. Hybrid male sterility in Mimulus (Phrymaceae) is associated with a geographically restricted mitochondrial rearrangement.

    PubMed

    Case, Andrea L; Willis, John H

    2008-05-01

    Cytoplasmic male sterility (CMS) and nuclear fertility restoration (Rf) involves intergenomic coevolution. Although male-sterile phenotypes are rarely expressed in natural populations of angiosperms, CMS genes are thought to be common. The evolutionary dynamics of CMS/Rf systems are poorly understood, leaving gaps in our understanding of mechanisms and consequences of cytonuclear interactions. We characterized the molecular basis and geographic distribution of a CMS gene in Mimulus guttatus. We used outcrossing M. guttatus (with CMS and Rf) to self-fertilizing M. nasutus (lacking CMS and Rf) to generate hybrids segregating for CMS. Mitochondrial transcripts containing an essential gene (nad6) were perfectly associated with male sterility. The CMS mitotype was completely absent in M. nasutus, present in all genotypes collected from the original collection site, but in only two individuals from 34 other M. guttatus populations. This pattern suggests that the CMS likely originated at a single locality, spread to fixation within the population, but has not spread to other populations, indicating possible ecological or genetic constraints on dispersal of this CMS mitotype between populations. Extreme localization may be characteristic of CMS in hermaphroditic species, in contrast to geographically widespread mitotypes commonly found in gynodioecious species, and could directly contribute to hybrid incompatibilities in nature.

  7. Angle-corrected imaging transcranial doppler sonography versus imaging and nonimaging transcranial doppler sonography in children with sickle cell disease.

    PubMed

    Krejza, J; Rudzinski, W; Pawlak, M A; Tomaszewski, M; Ichord, R; Kwiatkowski, J; Gor, D; Melhem, E R

    2007-09-01

    Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. A total of 37 children (mean age, 7.8 +/- 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31 degrees , 44 degrees , 25 degrees , and 29 degrees , respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean +/- SD): MCA, 106 +/- 22 cm/s and 111 +/- 33 cm/s versus 130 +/- 19 cm/s and 134 +/- 26 cm/s; ICA, 90 +/- 14 cm/s and 98 +/- 27 cm/s versus 117 +/- 18 cm/s and 119 +/- 23 cm/s; ACA, 74 +/- 24 cm/s and 88 +/- 25 cm/s versus 105 +/- 23 cm/s and 105 +/- 31 cm/s; and PCA, 84 +/- 27 cm/s and 82 +/- 21 cm/s versus 95 +/- 23 cm/s and 94 +/- 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD.

  8. 42 CFR 488.417 - Denial of payment for all new admissions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

  9. 42 CFR 488.417 - Denial of payment for all new admissions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

  10. 42 CFR 488.417 - Denial of payment for all new admissions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

  11. 42 CFR 488.417 - Denial of payment for all new admissions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

  12. 42 CFR 488.417 - Denial of payment for all new admissions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

  13. 45 CFR 150.317 - Factors CMS uses to determine the amount of penalty.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Factors CMS uses to determine the amount of... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.317 Factors CMS...

  14. 40 CFR Table 1 to Subpart Qqqqq of... - Applicability of General Provisions to Subpart QQQQQ

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... § 63.8(e) CMS Performance Evaluation No Subpart QQQQQ does not require CMS performance evaluations... QQQQQ does not require performance tests or CMS performance evaluations. § 63.9(e) Notification of... CMS No Subpart QQQQQ does not require CMS performance evaluations. § 63.10(a), (b), (d)(1), (d)(4)-(5...

  15. 42 CFR 405.753 - Appeal of a categorization of a device.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Appeal of a categorization of a device. 405.753... Under Medicare Part A § 405.753 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

  16. 42 CFR 405.877 - Appeal of a categorization of a device.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Appeal of a categorization of a device. 405.877... Part B Program § 405.877 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

  17. 42 CFR 405.877 - Appeal of a categorization of a device.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Appeal of a categorization of a device. 405.877... Part B Program § 405.877 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

  18. 42 CFR 405.753 - Appeal of a categorization of a device.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Appeal of a categorization of a device. 405.753... Under Medicare Part A § 405.753 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

  19. The High-Luminosity upgrade of the LHC: Physics and Technology Challenges for the Accelerator and the Experiments

    NASA Astrophysics Data System (ADS)

    Schmidt, Burkhard

    2016-04-01

    In the second phase of the LHC physics program, the accelerator will provide an additional integrated luminosity of about 2500/fb over 10 years of operation to the general purpose detectors ATLAS and CMS. This will substantially enlarge the mass reach in the search for new particles and will also greatly extend the potential to study the properties of the Higgs boson discovered at the LHC in 2012. In order to meet the experimental challenges of unprecedented pp luminosity, the experiments will need to address the aging of the present detectors and to improve the ability to isolate and precisely measure the products of the most interesting collisions. The lectures gave an overview of the physics motivation and described the conceptual designs and the expected performance of the upgrades of the four major experiments, ALICE, ATLAS, CMS and LHCb, along with the plans to develop the appropriate experimental techniques and a brief overview of the accelerator upgrade. Only some key points of the upgrade program of the four major experiments are discussed in this report; more information can be found in the references given at the end.

  20. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Application Procedures and Contracts for Medicare Advantage Organizations § 422.510 Termination of contract by CMS. (a) Termination by CMS. CMS may at any...

  1. The diverse use of clouds by CMS

    DOE PAGES

    Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; ...

    2015-12-23

    The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of themore » trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources. Lastly, we present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.« less

  2. The Status of the Cms Experiment

    NASA Astrophysics Data System (ADS)

    Green, Dan

    The CMS experiment was completely assembled in the fall of 2008 after a decade of design, construction and installation. During the last two years, cosmic ray data were taken on a regular basis. These data have enabled CMS to align the detector components, both spatially and temporally. Initial use of muons has also established the relative alignment of the CMS tracking and muon systems. In addition, the CMS calorimetry has been crosschecked with test beam data, thus providing an initial energy calibration of CMS calorimetry to about 5%. The CMS magnet has been powered and field mapped. The trigger and data acquisition systems have been installed and run at full speed. The tiered data analysis system has been exercised at full design bandwidth for Tier0, Tier1 and Tier2 sites. Monte Carlo simulation of the CMS detector has been constructed at a detailed geometric level and has been tuned to test beam and other production data to provide a realistic model of the CMS detector prior to first collisions.

  3. Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

    2017-03-09

    Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.

  4. Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

    PubMed Central

    Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

    2014-01-01

    Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

  5. 42 CFR 426.415 - CMS' role in the LCD review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' role in the LCD review. 426.415 Section 426... Review of an LCD § 426.415 CMS' role in the LCD review. CMS may provide to the ALJ, and all parties to the LCD review, information identifying the person who represents the contractor or CMS, if necessary...

  6. CMS-Wave

    DTIC Science & Technology

    2015-10-30

    Coastal Inlets Research Program CMS -Wave CMS -Wave is a two-dimensional spectral wind-wave generation and transformation model that employs a forward...marching, finite-difference method to solve the wave action conservation equation. Capabilities of CMS -Wave include wave shoaling, refraction... CMS -Wave can be used in either on a half- or full-plane mode, with primary waves propagating from the seaward boundary toward shore. It can

  7. A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli

    PubMed Central

    Liu, Taoyan; Huang, Chengwu; Li, Hongxia; Wu, Fujian; Luo, Jianwen; Lu, Wenjing

    2018-01-01

    The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the differently shaped CMs, and the net-shaped CMs had larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net-shaped CMs displayed accelerated maturation at the transcriptional level and were more similar to CMs with a prolonged culture time (30 days) than to sheet-d15. Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs, indicating that robust contraction was coupled with enhanced ion channel and connexin expression. The net-shaped CMs also displayed improved myofibril ultrastructure under transmission electron microscopy. In conclusion, different multicellular hPSC-CM structures, such as the net-shaped pattern, are formed using the conditioned induction method, providing a useful tool to improve cardiac maturation. PMID:29661985

  8. A Predictive Model for Readmissions Among Medicare Patients in a California Hospital.

    PubMed

    Duncan, Ian; Huynh, Nhan

    2017-11-17

    Predictive models for hospital readmission rates are in high demand because of the Centers for Medicare & Medicaid Services (CMS) Hospital Readmission Reduction Program (HRRP). The LACE index is one of the most popular predictive tools among hospitals in the United States. The LACE index is a simple tool with 4 parameters: Length of stay, Acuity of admission, Comorbidity, and Emergency visits in the previous 6 months. The authors applied logistic regression to develop a predictive model for a medium-sized not-for-profit community hospital in California using patient-level data with more specific patient information (including 13 explanatory variables). Specifically, the logistic regression is applied to 2 populations: a general population including all patients and the specific group of patients targeted by the CMS penalty (characterized as ages 65 or older with select conditions). The 2 resulting logistic regression models have a higher sensitivity rate compared to the sensitivity of the LACE index. The C statistic values of the model applied to both populations demonstrate moderate levels of predictive power. The authors also build an economic model to demonstrate the potential financial impact of the use of the model for targeting high-risk patients in a sample hospital and demonstrate that, on balance, whether the hospital gains or loses from reducing readmissions depends on its margin and the extent of its readmission penalties.

  9. Human renal adipose tissue induces the invasion and progression of renal cell carcinoma.

    PubMed

    Campo-Verde-Arbocco, Fiorella; López-Laur, José D; Romeo, Leonardo R; Giorlando, Noelia; Bruna, Flavia A; Contador, David E; López-Fontana, Gastón; Santiano, Flavia E; Sasso, Corina V; Zyla, Leila E; López-Fontana, Constanza M; Calvo, Juan C; Carón, Rubén W; Creydt, Virginia Pistone

    2017-11-07

    We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.

  10. Down-regulation of Inwardly Rectifying K+ Currents in Astrocytes Derived from Patients with Monge's Disease.

    PubMed

    Wu, Wei; Yao, Hang; Zhao, Helen W; Wang, Juan; Haddad, Gabriel G

    2018-03-15

    Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders. These patients have a variety of neurologic symptoms such as migraine, mental fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal degeneration. The cellular and molecular mechanisms underlying CMS neuropathology is not understood. In the previous study, we demonstrated that neurons derived from CMS patients' fibroblasts have a decreased expression and altered gating properties of voltage-gated sodium channel. In this study, we further characterize the electrophysiological properties of iPSC-derived astrocytes from CMS patients. We found that the current densities of the inwardly rectifying potassium (Kir) channels in CMS astrocytes (-5.7 ± 2.2 pA/pF at -140 mV) were significantly decreased as compared to non-CMS (-28.4 ± 3.4 pA/pF at -140 mV) and sea level subjects (-28.3 ± 5.3 pA/pF at -140 mV). We further demonstrated that the reduced Kir current densities in CMS astrocytes were caused by their decreased protein expression of Kir4.1 and Kir2.3 channels, while single channel properties (i.e., P o , conductance) of Kir channel in CMS astrocytes were not altered. In addition, we found no significant differences of outward potassium currents between CMS and non-CMS astrocytes. As compared to non-CMS and sea level subjects, the K + uptake ability in CMS astrocytes was significantly decreased. Taken together, our results suggest that down-regulation of Kir channels and the resulting decreased K + uptake ability in astrocytes could be one of the major molecular mechanisms underlying the neurologic manifestations in CMS patients. Published by Elsevier Ltd.

  11. From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Peinkofer, Gabriel; Burkert, Karsten; Urban, Katja; Krausgrill, Benjamin; Hescheler, Jürgen; Saric, Tomo; Halbach, Marcel

    2016-10-01

    Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPS-CMs) are promising candidates for cell therapy, drug screening, and developmental studies. It is known that iPS-CMs possess immature electrophysiological properties, but an exact characterization of their developmental stage and subtype differentiation is hampered by a lack of knowledge of electrophysiological properties of native CMs from different developmental stages and origins within the heart. Thus, we sought to systematically investigate action potential (AP) properties of native murine CMs and to establish a database that allows classification of stem cell-derived CMs. Hearts from 129S2PasCrl mice were harvested at days 9-10, 12-14, and 16-18 postcoitum, as well as 1 day, 3-4 days, 1-2 weeks, 3-4 weeks, and 6 weeks postpartum. AP recordings in left and right atria and at apical, medial, and basal left and right ventricles were performed with sharp glass microelectrodes. Measurements revealed significant changes in AP morphology during pre- and postnatal murine development and significant differences between atria and ventricles, enabling a classification of developmental stage and subtype differentiation of stem cell-derived CMs based on their AP properties. For iPS-CMs derived from cell line TiB7.4, a typical ventricular phenotype was demonstrated at later developmental stages, while there were electrophysiological differences from atrial as well as ventricular native CMs at earlier stages. This finding supports that iPS-CMs can develop AP properties similar to native CMs, but points to differences in the maturation process between iPS-CMs and native CMs, which may be explained by dissimilar conditions during in vitro differentiation and in vivo development.

  12. Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

    PubMed

    Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

    2018-05-01

    The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  13. Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii.

    PubMed

    Luque, Sònia; Grau, Santiago; Valle, Marta; Sorlí, Luisa; Horcajada, Juan Pablo; Segura, Concha; Alvarez-Lerma, Francisco

    2013-08-01

    Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  14. Effect of an emergency department fast track on Press-Ganey patient satisfaction scores.

    PubMed

    Hwang, Calvin E; Lipman, Grant S; Kane, Marlena

    2015-01-01

    Mandated patient surveys have become an integral part of Medicare remuneration, putting hundreds of millions of dollars in funding at risk. The Centers for Medicare & Medicaid Services (CMS) recently announced a patient experience survey for the emergency department (ED). Development of an ED Fast Track, where lower acuity patients are rapidly seen, has been shown to improve many of the metrics that CMS examines. This is the first study examining if ED Fast Track implementation affects Press-Ganey scores of patient satisfaction. We analyzed returned Press-Ganey questionnaires from all ESI 4 and 5 patients seen 11AM - 1PM, August-December 2011 (pre-fast track), and during the identical hours of fast track, August-December 2012. Raw ordinal scores were converted to continuous scores for paired student t-test analysis. We calculated an odds ratio with 100% satisfaction considered a positive response. An academic ED with 52,000 annual visits had 140 pre-fast track and 85 fast track respondents. Implementation of a fast track significantly increased patient satisfaction with the following: wait times (68% satisfaction to 88%, OR 4.13, 95% CI [2.32-7.33]), doctor courtesy (90% to 95%, OR 1.97, 95% CI [1.04-3.73]), nurse courtesy (87% to 95%, OR 2.75, 95% CI [1.46-5.15]), pain control (79% to 87%, OR 2.13, 95% CI [1.16-3.92]), likelihood to recommend (81% to 90%, OR 2.62, 95% CI [1.42-4.83]), staff caring (82% to 91%, OR 2.82, 95% CI [1.54-5.19]), and staying informed about delays (66% to 83%, OR 3.00, 95% CI [1.65-5.44]). Implementation of an ED Fast Track more than doubled the odds of significant improvements in Press-Ganey patient satisfaction metrics and may play an important role in improving ED performance on CMS benchmarks.

  15. IL-21 promotes myocardial ischaemia/reperfusion injury through the modulation of neutrophil infiltration.

    PubMed

    Wang, Kejing; Wen, Shuang; Jiao, Jiao; Tang, Tingting; Zhao, Xin; Zhang, Min; Lv, Bingjie; Lu, Yuzhi; Zhou, Xingdi; Li, Jingyong; Nie, Shaofang; Liao, Yuhua; Wang, Qing; Tu, Xin; Mallat, Ziad; Xia, Ni; Cheng, Xiang

    2018-04-01

    The immune system plays an important role in driving the acute inflammatory response following myocardial ischaemia/reperfusion injury (MIRI). IL-21 is a pleiotropic cytokine with multiple immunomodulatory effects, but its role in MIRI is not known. Myocardial injury, neutrophil infiltration and the expression of neutrophil chemokines KC (CXCL1) and MIP-2 (CXCL2) were studied in a mouse model of MIRI. Effects of IL-21 on the expression of KC and MIP-2 in neonatal mouse cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were determined by real-time PCR and ELISA. The signalling mechanisms underlying these effects were explored by western blot analysis. IL-21 was elevated within the acute phase of murine MIRI. Neutralization of IL-21 attenuated myocardial injury, as illustrated by reduced infarct size, decreased cardiac troponin T levels and improved cardiac function, whereas exogenous IL-21 administration exerted opposite effects. IL-21 increased the infiltration of neutrophils and increased the expression of KC and MIP-2 in myocardial tissue following MIRI. Moreover, neutrophil depletion attenuated the IL-21-induced myocardial injury. Mechanistically, IL-21 increased the production of KC and MIP-2 in neonatal CMs and CFs, and enhanced neutrophil migration, as revealed by the migration assay. Furthermore, we demonstrated that this IL-21-mediated increase in chemokine expression involved the activation of Akt/NF-κB signalling in CMs and p38 MAPK/NF-κB signalling in CFs. Our data provide novel evidence that IL-21 plays a pathogenic role in MIRI, most likely by promoting cardiac neutrophil infiltration. Therefore, targeting IL-21 may have therapeutic potential as a treatment for MIRI. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

  16. Structural and Functional Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells

    PubMed Central

    Lundy, Scott D.; Zhu, Wei-Zhong

    2013-01-01

    Despite preclinical studies demonstrating the functional benefit of transplanting human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) into damaged myocardium, the ability of these immature cells to adopt a more adult-like cardiomyocyte (CM) phenotype remains uncertain. To address this issue, we tested the hypothesis that prolonged in vitro culture of human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived CMs would result in the maturation of their structural and contractile properties to a more adult-like phenotype. Compared to their early-stage counterparts (PSC-CMs after 20–40 days of in vitro differentiation and culture), late-stage hESC-CMs and hiPSC-CMs (80–120 days) showed dramatic differences in morphology, including increased cell size and anisotropy, greater myofibril density and alignment, sarcomeres visible by bright-field microscopy, and a 10-fold increase in the fraction of multinucleated CMs. Ultrastructural analysis confirmed improvements in the myofibrillar density, alignment, and morphology. We measured the contractile performance of late-stage hESC-CMs and hiPSC-CMs and noted a doubling in shortening magnitude with slowed contraction kinetics compared to the early-stage cells. We then examined changes in the calcium-handling properties of these matured CMs and found an increase in calcium release and reuptake rates with no change in the maximum amplitude. Finally, we performed electrophysiological assessments in hESC-CMs and found that late-stage myocytes have hyperpolarized maximum diastolic potentials, increased action potential amplitudes, and faster upstroke velocities. To correlate these functional changes with gene expression, we performed qPCR and found a robust induction of the key cardiac structural markers, including β-myosin heavy chain and connexin-43, in late-stage hESC-CMs and hiPSC-CMs. These findings suggest that PSC-CMs are capable of slowly maturing to more closely resemble the phenotype of adult CMs and may eventually possess the potential to regenerate the lost myocardium with robust de novo force-producing tissue. PMID:23461462

  17. CMS Connect

    NASA Astrophysics Data System (ADS)

    Balcas, J.; Bockelman, B.; Gardner, R., Jr.; Hurtado Anampa, K.; Jayatilaka, B.; Aftab Khan, F.; Lannon, K.; Larson, K.; Letts, J.; Marra Da Silva, J.; Mascheroni, M.; Mason, D.; Perez-Calero Yzquierdo, A.; Tiradani, A.

    2017-10-01

    The CMS experiment collects and analyzes large amounts of data coming from high energy particle collisions produced by the Large Hadron Collider (LHC) at CERN. This involves a huge amount of real and simulated data processing that needs to be handled in batch-oriented platforms. The CMS Global Pool of computing resources provide +100K dedicated CPU cores and another 50K to 100K CPU cores from opportunistic resources for these kind of tasks and even though production and event processing analysis workflows are already managed by existing tools, there is still a lack of support to submit final stage condor-like analysis jobs familiar to Tier-3 or local Computing Facilities users into these distributed resources in an integrated (with other CMS services) and friendly way. CMS Connect is a set of computing tools and services designed to augment existing services in the CMS Physics community focusing on these kind of condor analysis jobs. It is based on the CI-Connect platform developed by the Open Science Grid and uses the CMS GlideInWMS infrastructure to transparently plug CMS global grid resources into a virtual pool accessed via a single submission machine. This paper describes the specific developments and deployment of CMS Connect beyond the CI-Connect platform in order to integrate the service with CMS specific needs, including specific Site submission, accounting of jobs and automated reporting to standard CMS monitoring resources in an effortless way to their users.

  18. Ogura-CMS in Chinese cabbage (Brassica rapa ssp. pekinensis) causes delayed expression of many nuclear genes.

    PubMed

    Dong, Xiangshu; Kim, Wan Kyu; Lim, Yong-Pyo; Kim, Yeon-Ki; Hur, Yoonkang

    2013-02-01

    We investigated the mechanism regulating cytoplasmic male sterility (CMS) in Brassica rapa ssp. pekinensis using floral bud transcriptome analyses of Ogura-CMS Chinese cabbage and its maintainer line in B. rapa 300-K oligomeric probe (Br300K) microarrays. Ogura-CMS Chinese cabbage produced few and infertile pollen grains on indehiscent anthers. Compared to the maintainer line, CMS plants had shorter filaments and plant growth, and delayed flowering and pollen development. In microarray analysis, 4646 genes showed different expression, depending on floral bud size, between Ogura-CMS and its maintainer line. We found 108 and 62 genes specifically expressed in Ogura-CMS and its maintainer line, respectively. Ogura-CMS line-specific genes included stress-related, redox-related, and B. rapa novel genes. In the maintainer line, genes related to pollen coat and germination were specifically expressed in floral buds longer than 3mm, suggesting insufficient expression of these genes in Ogura-CMS is directly related to dysfunctional pollen. In addition, many nuclear genes associated with auxin response, ATP synthesis, pollen development and stress response had delayed expression in Ogura-CMS plants compared to the maintainer line, which is consistent with the delay in growth and development of Ogura-CMS plants. Delayed expression may reduce pollen grain production and/or cause sterility, implying that mitochondrial, retrograde signaling delays nuclear gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

    PubMed

    Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

    2011-11-01

    CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The impact of LHC jet data on the MMHT PDF fit at NNLO

    NASA Astrophysics Data System (ADS)

    Harland-Lang, L. A.; Martin, A. D.; Thorne, R. S.

    2018-03-01

    We investigate the impact of the high precision ATLAS and CMS 7 TeV measurements of inclusive jet production on the MMHT global PDF analysis at next-to-next-to-leading order (NNLO). This is made possible by the recent completion of the long-term project to calculate the NNLO corrections to the hard cross section. We find that a good description of the ATLAS data is not possible with the default treatment of experimental systematic errors, and propose a simplified solution that retains the dominant physical information of the data. We then investigate the fit quality and the impact on the gluon PDF central value and uncertainty when the ATLAS and CMS data are included in a MMHT fit. We consider both common choices for the factorization and renormalization scale, namely the inclusive jet transverse momentum, p_\\perp , and the leading jet p_\\perp , as well as the different jet radii for which the ATLAS and CMS data are made available. We find that the impact of these data on the gluon is relatively insensitive to these inputs, in particular the scale choice, while the inclusion of NNLO corrections tends to improve the data description somewhat and has a qualitatively similar though not identical impact on the gluon in comparison to NLO.

  1. Construction and performance of a long-term earthen liner experiment

    USGS Publications Warehouse

    Cartwright, Keros; Krapac, Ivan G.; Bonaparte, Rudolph

    1990-01-01

    In land burial schemes, compacted soil barriers with low hydraulic conductivity are commonly used in cover and liner systems to control the movement of liquids and prevent groundwater contamination. An experimental liner measuring 8 x 15 x 0.9 m was constructed with design criteria and equipment to simulate construction of soil liners built at waste disposal facilities. The surface of the liner was flooded with a 29.5 cm deep pond on April 12, 1988. Infiltration of water into the liner has been monitored for two years using 4 large-ring (1.5 m OD) and 32 small-ring (0.28 m OD) infiltrometers, and a water-balance that accounts for total infiltration and evaporation. Average long-term infiltration fluxes based on two years of monitoring are 5.8 x 10-9 cm/s, 6.0 x 10-8 cm/s and 5.6 x 10-8 for the large-ring, small-ring, and water-balance data, respectively. The saturated hydraulic conductivity of the liner based on small-ring data, estimated using Darcy's Law and the Green-Ampt Approximation, is 3 x 10-8 and 4 x 10-8 cm/s, respectively. All sets of data indicate that the liner's performance exceed that which is required by the U.S. EPA.

  2. Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt

    NASA Technical Reports Server (NTRS)

    Kawai, Y.; Murthy, G.; Watenpaugh, D. E.; Breit, G. A.; Deroshia, C. W.; Hargens, A. R.

    1993-01-01

    This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 deg head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT, reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for over 6 h of HDT. During upright seated recovery, mean CBF velocity decreased to 87 percent of the pre-HDT baseline value. Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth.

  3. 42 CFR 411.382 - CMS's right to rescind advisory opinions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... rescind advisory opinions. Any advice CMS gives in an opinion does not prejudice its right to reconsider... faith reliance upon CMS's advice under this part, provided— (a) The requestor presented to CMS a full...

  4. 42 CFR 411.382 - CMS's right to rescind advisory opinions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... rescind advisory opinions. Any advice CMS gives in an opinion does not prejudice its right to reconsider... faith reliance upon CMS's advice under this part, provided— (a) The requestor presented to CMS a full...

  5. Comparative analysis of mitochondrial genomes between the hau cytoplasmic male sterility (CMS) line and its iso-nuclear maintainer line in Brassica juncea to reveal the origin of the CMS-associated gene orf288.

    PubMed

    Heng, Shuangping; Wei, Chao; Jing, Bing; Wan, Zhengjie; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Shen, Jinxiong

    2014-04-30

    Cytoplasmic male sterility (CMS) is not only important for exploiting heterosis in crop plants, but also as a model for investigating nuclear-cytoplasmic interaction. CMS may be caused by mutations, rearrangement or recombination in the mitochondrial genome. Understanding the mitochondrial genome is often the first and key step in unraveling the molecular and genetic basis of CMS in plants. Comparative analysis of the mitochondrial genome of the hau CMS line and its maintainer line in B. juneca (Brassica juncea) may help show the origin of the CMS-associated gene orf288. Through next-generation sequencing, the B. juncea hau CMS mitochondrial genome was assembled into a single, circular-mapping molecule that is 247,903 bp in size and 45.08% in GC content. In addition to the CMS associated gene orf288, the genome contains 35 protein-encoding genes, 3 rRNAs, 25 tRNA genes and 29 ORFs of unknown function. The mitochondrial genome sizes of the maintainer line and another normal type line "J163-4" are both 219,863 bp and with GC content at 45.23%. The maintainer line has 36 genes with protein products, 3 rRNAs, 22 tRNA genes and 31 unidentified ORFs. Comparative analysis the mitochondrial genomes of the hau CMS line and its maintainer line allowed us to develop specific markers to separate the two lines at the seedling stage. We also confirmed that different mitotypes coexist substoichiometrically in hau CMS lines and its maintainer lines in B. juncea. The number of repeats larger than 100 bp in the hau CMS line (16 repeats) are nearly twice of those found in the maintainer line (9 repeats). Phylogenetic analysis of the CMS-associated gene orf288 and four other homologous sequences in Brassicaceae show that orf288 was clearly different from orf263 in Brassica tournefortii despite of strong similarity. The hau CMS mitochondrial genome was highly rearranged when compared with its iso-nuclear maintainer line mitochondrial genome. This study may be useful for studying the mechanism of natural CMS in B. juncea, performing comparative analysis on sequenced mitochondrial genomes in Brassicas, and uncovering the origin of the hau CMS mitotype and structural and evolutionary differences between different mitotypes.

  6. Opportunistic Resource Usage in CMS

    NASA Astrophysics Data System (ADS)

    Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.; Gutsche, O.; Tadel, M.; Sfiligoi, I.; Letts, J.; Wuerthwein, F.; McCrea, A.; Bockelman, B.; Fajardo, E.; Linares, L.; Wagner, R.; Konstantinov, P.; Blumenfeld, B.; Bradley, D.; Cms Collaboration

    2014-06-01

    CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliant cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.

  7. Quality compensation programs: are they worth all the hype? A comparison of outcomes within a Medicare advantage heart failure population.

    PubMed

    Esse, Tara; Serna, Omar; Chitnis, Abhishek; Johnson, Michael; Fernandez, Nelson

    2013-05-01

    Quality compensation programs (QCPs), also known as pay-for-performance programs, are becoming more common within managed care entities. QCPs are believed to yield better patient outcomes, yet the programs lack the evidence needed to support these claims. We evaluated a QCP offered to network primary care physicians (PCPs) within a Medicare managed care plan to determine if a positive correlation between outcomes and the program exists. To compare outcomes of heart failure members under the care of PCPs enrolled in a Medicare Advantage Prescription Drug (MAPD) Plan QCP with those who are not affiliated with a QCP. Retrospective analysis was conducted on the heart failure population of a MAPD in Texas. Heart failure members were identified using ICD-9-CM codes from inpatient and outpatient claims for 2010. These members must have been continuously eligible all 12 months of the year to be included in the analysis. The primary intervention was enrollment by the member's PCP into the QCP. Measurable outcomes included acute (hospital) admits, emergency room (ER) visits, appropriate laboratory tests, and prescriptions of medications that are evidence based and guideline driven. Centers for Medicare and Medicaid Services (CMS) risk scores and comorbidities were used to risk-adjust outcomes. A total of 4,240 members was included in the analysis. From that population, 1,225 members (28.8%) were followed by PCPs enrolled in a QCP; 3,015 members (71.1%) were followed by PCPs not enrolled in a QCP. The adjusted analysis showed that none of the drug comparisons statistically differed between the QCP and non-QCP groups, whereas all of the lab tests, including low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c, creatinine, and microalbumin, as well as the acquisition of the flu vaccine, occurred more frequently in the QCP group. Acute admits and ER visits in the QCP and non-QCP groups were similar before and after adjustment. The QCP group was significantly older with a statistically significant higher prevalence of renal failure and higher CMS risk scores. After evaluation of our QCP's impact on the quality of care provided to our Medicare beneficiaries, we have concluded that there is potential for health care improvement through pay-for-performance programs. We have observed in our MAPD heart failure population, enrolled in a QCP during the year of 2010, an increase in age and CMS risk scores, a decline in renal function, and noted the group to have a more female presence. Yet, the outcomes of this group (hospitalizations, ER visits, acquisition of lab tests, etc.) were similar when compared with younger, healthier members not enrolled in a QCP. We feel the clinical relevance of the data indicates that, overall, the quality of care is somewhat improved for QCP-enrolled providers when compared with non-QCP providers in regards to achieving certain quality metrics. (i.e., immunizations, HgA1c, LDL-C, etc.) Further research is definitely needed to determine if health care costs and clinical outcomes, in the long term, are improved for members enrolled in these QCP programs, as well as their impact upon a health plan's Medicare Star rating.

  8. Web Based Monitoring in the CMS Experiment at CERN

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

    Badgett, William; Borrello, Laura; Chakaberia, Irakli

    2014-09-03

    The Compact Muon Solenoid (CMS) is a large and complex general purpose experiment at the CERN Large Hadron Collider (LHC), built and maintained by many collaborators from around the world. Efficient operation of the detector requires widespread and timely access to a broad range of monitoring and status information. To this end the Web Based Monitoring (WBM) system was developed to present data to users located anywhere from many underlying heterogeneous sources, from real time messaging systems to relational databases. This system provides the power to combine and correlate data in both graphical and tabular formats of interest to themore » experimenters, including data such as beam conditions, luminosity, trigger rates, detector conditions, and many others, allowing for flexibility on the user side. This paper describes the WBM system architecture and describes how the system was used during the first major data taking run of the LHC.« less

  9. 42 CFR 405.1012 - When CMS or its contractors may be a party to a hearing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS or its contractors may be a party to a... Hearings § 405.1012 When CMS or its contractors may be a party to a hearing. (a) CMS and/or one or more of... unrepresented beneficiary. (b) CMS and/or the contractor(s) advises the ALJ, appellant, and all other parties...

  10. Development of Cytoplasmic Male Sterile IR24 and IR64 Using CW-CMS/Rf17 System.

    PubMed

    Toriyama, Kinya; Kazama, Tomohiko

    2016-12-01

    A wild-abortive-type (WA) cytoplasmic male sterility (CMS) has been almost exclusively used for breeding three-line hybrid rice. Many indica cultivars are known to carry restorer genes for WA-CMS lines and cannot be used as maintainer lines. Especially elite indica cultivars IR24 and IR64 are known to be restorer lines for WA-CMS lines, and are used as male parents for hybrid seed production. If we develop CMS IR24 and CMS IR64, the combination of F1 pairs in hybrid rice breeding programs will be greatly broadened. For production of CMS lines and restorer lines of IR24 and IR64, we employed Chinese wild rice (CW)-type CMS/Restorer of fertility 17 (Rf17) system, in which fertility is restored by a single nuclear gene, Rf17. Successive backcrossing and marker-assisted selection of Rf17 succeeded to produce completely male sterile CMS lines and fully restored restorer lines of IR24 and IR64. CW-cytoplasm did not affect agronomic characteristics. Since IR64 is one of the most popular mega-varieties and used for breeding of many modern varieties, the CW-CMS line of IR64 will be useful for hybrid rice breeding.

  11. Final Technical Report for ``Paths to Discovery at the LHC : Dark Matter and Track Triggering"

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

    Hahn, Kristian

    Particle Dark Matter (DM) is perhaps the most compelling and experimentally well-motivated new physics scenario anticipated at the Large Hadron Collider (LHC). The DE-SC0014073 award allowed the PI to define and pursue a path to the discovery of Dark Matter in Run-2 of the LHC with the Compact Muon Solenoid (CMS) experiment. CMS can probe regions of Dark Matter phase-space that direct and indirect detection experiments are unable to constrain. The PI’s team initiated the exploration of these regions, searching specifically for the associated production of Dark Matter with top quarks. The effort focuses on the high-yield, hadronic decays ofmore » W bosons produced in top decay, which provides the highest sensitivity to DM produced via through low-mass spin-0 mediators. The group developed identification algorithms that achieve high efficiency and purity in the selection of hadronic top decays, and analysis techniques that provide powerful signal discrimination in Run-2. The ultimate reach of new physics searches with CMS will be established at the high-luminosity LHC (HL-LHC). To fully realize the sensitivity the HL-LHC promises, CMS must minimize the impact of soft, inelastic (“pileup”) interactions on the real-time “trigger” system the experiment uses for data refinement. Charged particle trajectory information (“tracking”) will be essential for pileup mitigation at the HL-LHC. The award allowed the PI’s team to develop firmware-based data delivery and track fitting algorithms for an unprecedented, real-time tracking trigger to sustain the experiment’s sensitivity to new physics in the next decade.« less

  12. Hydro-meteorologic assessment of October 2015 extreme precipitation event on Santee Experimental Forest Watersheds, South Carolina

    Treesearch

    D.M. Amatya; C.A. Harrison; C.C. Trettin

    2016-01-01

    The extreme precipitation event on October 3-4, 2015, likely resulting from the convergence of a persistent deep easterly flow, the continuous supply of moisture, the terrain, and the circulation associated with Hurricane Joaquin off the eastern Atlantic Coast (http://cms.met.psu. edu/sref/severe/2015/04Oct2015.pdf) resulted in extreme and prolonged flooding in many...

  13. 42 CFR 414.68 - Imaging accreditation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

  14. 42 CFR 414.68 - Imaging accreditation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

  15. 42 CFR 414.68 - Imaging accreditation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

  16. Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior.

    PubMed

    Mandel, Yael; Weissman, Amir; Schick, Revital; Barad, Lili; Novak, Atara; Meiry, Gideon; Goldberg, Stanislav; Lorber, Avraham; Rosen, Michael R; Itskovitz-Eldor, Joseph; Binah, Ofer

    2012-02-21

    The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node. We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs. This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-law behavior as in humans, thus supporting the potential capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient's own hair (via keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.

  17. Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

    PubMed Central

    Campo-Verde-Arbocco, Fiorella; López-Laur, José D.; Romeo, Leonardo R.; Giorlando, Noelia; Bruna, Flavia A.; Contador, David E.; López-Fontana, Gastón; Santiano, Flavia E.; Sasso, Corina V.; Zyla, Leila E.; López-Fontana, Constanza M.; Calvo, Juan C.; Carón, Rubén W.; Creydt, Virginia Pistone

    2017-01-01

    We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease. PMID:29212223

  18. Mitochondrial nad2 gene is co-transcripted with CMS-associated orfB gene in cytoplasmic male-sterile stem mustard (Brassica juncea).

    PubMed

    Yang, Jing-Hua; Zhang, Ming-Fang; Yu, Jing-Quan

    2009-02-01

    The transcriptional patterns of mitochondrial respiratory related genes were investigated in cytoplasmic male-sterile and fertile maintainer lines of stem mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel open reading frame, hereafter named orfB gene, was located at the downstream of mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220 gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified by primers of nad2F and nad2R from CMS) were found in the CMS line following Southern blotting digested with HindIII, but only a single copy in its maintainer line. Meanwhile, two transcripts were shown in the CMS line following Northern blotting while only one transcript was detected in the maintainer line, which were probed by specific fragment (amplified by primers of nad2F and nad2R from CMS). Meanwhile, the expression of nad2 gene was reduced in CMS bud compared to that in its maintainer line. We thus suggested that nad2 gene may be co-transcripted with CMS-associated orfB gene in the CMS. In addition, the specific fragment that was amplified by primers of nad2F and nad2R just spanned partial sequences of nad2 gene and orfB gene. Such alterations in the nad2 gene would impact the activity of NADH dehydrogenase, and subsequently signaling, inducing the expression of nuclear genes involved in male sterility in this type of cytoplasmic male sterility.

  19. Responding to GPs' information resource needs: implementation and evaluation of a complementary medicines information resource in Queensland general practice

    PubMed Central

    2011-01-01

    Background Australian General Practitioners (GPs) are in the forefront of primary health care and in an excellent position to communicate with their patients and educate them about Complementary Medicines (CMs) use. However previous studies have demonstrated that GPs lack the knowledge required about CMs to effectively communicate with patients about their CMs use and they perceive a need for information resources on CMs to use in their clinical practice. This study aimed to develop, implement, and evaluate a CMs information resource in Queensland (Qld) general practice. Methods The results of the needs assessment survey of Qld general practitioners (GPs) informed the development of a CMs information resource which was then put through an implementation and evaluation cycle in Qld general practice. The CMs information resource was a set of evidence-based herbal medicine fact sheets. This resource was utilised by 100 Qld GPs in their clinical practice for four weeks and was then evaluated. The evaluation assessed GPs' (1) utilisation of the resource (2) perceived quality, usefulness and satisfaction with the resource and (3) perceived impact of the resource on their knowledge, attitudes, and practice of CMs. Results Ninety two out of the 100 GPs completed the four week evaluation of the fact sheets and returned the post-intervention survey. The herbal medicine fact sheets produced by this study were well accepted and utilised by Qld GPs. The majority of GPs perceived that the fact sheets were a useful resource for their clinical practice. The fact sheets improved GPs' attitudes towards CMs, increased their knowledge of those herbal medicines and improved their communication with their patients about those specific herbs. Eighty-six percent of GPs agreed that if they had adequate resources on CMs, like the herbal medicine fact sheets, then they would communicate more to their patients about their use of CMs. Conclusion Further educational interventions on CMs need to be provided to GPs to increase their knowledge of CMs and to improve their communication with patients about their CMs use. PMID:21933434

  20. CMS results in the Combined Computing Readiness Challenge CCRC'08

    NASA Astrophysics Data System (ADS)

    Bonacorsi, D.; Bauerdick, L.; CMS Collaboration

    2009-12-01

    During February and May 2008, CMS participated to the Combined Computing Readiness Challenge (CCRC'08) together with all other LHC experiments. The purpose of this worldwide exercise was to check the readiness of the Computing infrastructure for LHC data taking. Another set of major CMS tests called Computing, Software and Analysis challenge (CSA'08) - as well as CMS cosmic runs - were also running at the same time: CCRC augmented the load on computing with additional tests to validate and stress-test all CMS computing workflows at full data taking scale, also extending this to the global WLCG community. CMS exercised most aspects of the CMS computing model, with very comprehensive tests. During May 2008, CMS moved more than 3.6 Petabytes among more than 300 links in the complex Grid topology. CMS demonstrated that is able to safely move data out of CERN to the Tier-1 sites, sustaining more than 600 MB/s as a daily average for more than seven days in a row, with enough headroom and with hourly peaks of up to 1.7 GB/s. CMS ran hundreds of simultaneous jobs at each Tier-1 site, re-reconstructing and skimming hundreds of millions of events. After re-reconstruction the fresh AOD (Analysis Object Data) has to be synchronized between Tier-1 centers: CMS demonstrated that the required inter-Tier-1 transfers are achievable within a few days. CMS also showed that skimmed analysis data sets can be transferred to Tier-2 sites for analysis at sufficient rate, regionally as well as inter-regionally, achieving all goals in about 90% of >200 links. Simultaneously, CMS also ran a large Tier-2 analysis exercise, where realistic analysis jobs were submitted to a large set of Tier-2 sites by a large number of people to produce a chaotic workload across the systems, and with more than 400 analysis users in May. Taken all together, CMS routinely achieved submissions of 100k jobs/day, with peaks up to 200k jobs/day. The achieved results in CCRC'08 - focussing on the distributed workflows - are presented and discussed.

  1. Repeated asenapine treatment does not participate in the mild stress induced FosB/ΔFosB expression in the rat hypothalamic paraventricular nucleus neurons.

    PubMed

    Kiss, Alexander; Majercikova, Zuzana

    2017-02-01

    Effect of repeated asenapine (ASE) treatment on FosB/ΔFosB expression was studied in the hypothalamic paraventricular nucleus (PVN) of male rats exposed to chronic mild stress (CMS) for 21days. Our intention was to find out whether repeated ASE treatment for 14days may: 1) induce FosB/ΔFosB expression in the PVN; 2) activate selected PVN neuronal phenotypes, synthesizing oxytocin (OXY), vasopressin (AVP), corticoliberin (CRH) or tyrosine hydroxylase (TH); and 3) interfere with the impact of CMS. Control, ASE, CMS, and CMS+ASE treated groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. From the 7th day of CMS, rats received ASE (0.3mg/kg) or saline (300μl/rat) subcutaneously, twice a day for 14days. They were sacrificed on the day 22nd (16-18h after last treatments). FosB/ΔFosB was visualized with avidin biotin peroxidase complex and OXY, AVP, CRH or TH antibodies by fluorescent dyes. Saline and ASE did not promote FosB/ΔFosB expression in the PVN. CMS and CMS+ASE elicited FosB/ΔFosB-expression in the PVN, whereas, ASE did not augment or attenuate FosB/ΔFosB induction elicited by CMS. FosB/ΔFosB-CRH occurred after CMS and CMS+ASE treatments in the PVN middle sector, while FosB/ΔFosB-AVP and FosB/ΔFosB-OXY after CMS and CMS+ASE treatments in the PVN posterior sector. FosB/ΔFosB-TH colocalization was rare. Larger FosB/ΔFosB profiles, running above the PVN, did not show any colocalizations. The study provides an anatomical/functional knowledge about an unaccented nature of prolonged ASE treatment at the level of PVN and excludes its positive or negative interplay with CMS effect. Data indicate that long-lasting ASE treatment might not act as a stressor acting at the PVN level. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The elution of colistimethate sodium from polymethylmethacrylate and calcium phosphate cement beads.

    PubMed

    Waterman, Paige; Barber, Melissa; Weintrob, Amy C; VanBrakle, Regina; Howard, Robin; Kozar, Michael P; Andersen, Romney; Wortmann, Glenn

    2012-06-01

    Gram-negative bacilli resistance to all antibiotics, except for colistimethate sodium (CMS), is an emerging healthcare concern. Incorporating CMS into orthopedic cement to treat bone and soft-tissue infections due to these bacteria is attractive, but the data regarding the elution of CMS from cement are conflicting. The in vitro analysis of the elution of CMS from polymethylmethacrylate (PMMA) and calcium phosphate (CP) cement beads is reported. PMMA and CP beads containing CMS were incubated in phosphate-buffered saline and the eluate sampled at sequential time points. The inhibition of the growth of a strain of Acinetobacter baumannii complex by the eluate was measured by disk diffusion and microbroth dilution assays, and the presence of CMS in the eluate was measured by mass spectroscopy. Bacterial growth was inhibited by the eluate from both PMMA and CP beads. Mass spectroscopy demonstrated greater elution of CMS from CP beads than PMMA beads. The dose of CMS in PMMA beads was limited by failure of bead integrity. CMS elutes from both CP and PMMA beads in amounts sufficient to inhibit bacterial growth in vitro. The clinical implications of these findings require further study.

  3. Opportunistic Resource Usage in CMS

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

    Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.

    2014-01-01

    CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliantmore » cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.« less

  4. 42 CFR 423.890 - Appeals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sponsor or by CMS before notice of the reconsidered determination is made. (6) Decision of the informal written reconsideration. CMS informs the sponsor of the decision orally or through electronic mail. CMS sends a written decision to the sponsor on the sponsor's request. (7) Effect of CMS informal written...

  5. 45 CFR 150.221 - Transition to State enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for... State enforcement. (a) If CMS determines that a State for which it has assumed enforcement authority has... appropriate to return enforcement authority to the State, CMS will enter into discussions with State officials...

  6. 45 CFR 150.213 - Form and content of notice.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... consequence of a State's failure to substantially enforce HIPAA requirements is that CMS enforces them. (d... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

  7. 45 CFR 150.321 - Determining the amount of penalty-aggravating circumstances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement..., if there are substantial or several aggravating circumstances, CMS sets the aggregate amount of the.... CMS considers the following circumstances to be aggravating circumstances: (a) The frequency of...

  8. 45 CFR 150.343 - Notice of proposed penalty.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.343 Notice of proposed penalty. If CMS... penalty. The notice includes the following: (a) A description of the HIPAA requirements that CMS has...

  9. CMS-G from Beta vulgaris ssp. maritima is maintained in natural populations despite containing an atypical cytochrome c oxidase.

    PubMed

    Meyer, Etienne H; Lehmann, Caroline; Boivin, Stéphane; Brings, Lea; De Cauwer, Isabelle; Bock, Ralph; Kühn, Kristina; Touzet, Pascal

    2018-02-23

    While mitochondrial mutants of the respiratory machinery are rare and often lethal, cytoplasmic male sterility (CMS), a mitochondrially inherited trait that results in pollen abortion, is frequently encountered in wild populations. It generates a breeding system called gynodioecy. In Beta vulgaris ssp. maritima , a gynodioecious species, we found CMS-G to be widespread across the distribution range of the species. Despite the sequencing of the mitochondrial genome of CMS-G, the mitochondrial sterilizing factor causing CMS-G is still unknown. By characterizing biochemically CMS-G, we found that the expression of several mitochondrial proteins is altered in CMS-G plants. In particular, Cox1, a core subunit of the cytochrome c oxidase (complex IV), is larger but can still assemble into complex IV. However, the CMS-G-specific complex IV was only detected as a stabilized dimer. We did not observe any alteration of the affinity of complex IV for cytochrome c ; however, in CMS-G, complex IV capacity is reduced. Our results show that CMS-G is maintained in many natural populations despite being associated with an atypical complex IV. We suggest that the modified complex IV could incur the associated cost predicted by theoretical models to maintain gynodioecy in wild populations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  10. Cardiometabolic syndrome and its association with education, smoking, diet, physical activity, and social support: findings from the Pennsylvania 2007 BRFSS Survey.

    PubMed

    Liu, Longjian; Núñez, Ana E

    2010-07-01

    The authors aimed to examine the prevalence of cardiometabolic syndrome (CMS) and its association with education, smoking, diet, physical activity, and social support among white, black, and Hispanic adults using data from the 2007 Pennsylvania Behavior Risk Factor Surveillance System (BRFSS) survey, the largest population-based survey in the state. The authors examined associations between CMS and associated factors cross-sectionally using univariate and multivariate methods. The study included a representative sample of 12,629 noninstitutionalized Pennsylvanians aged > or =18. Components of CMS included obesity, hypercholesterolemia, angina (as a surrogate for decreased high-density lipoprotein), prehypertension or hypertension, and prediabetes or diabetes. CMS was identified as the presence of > or =3 CMS components. The results show that the prevalence of CMS was 20.48% in blacks, followed by Hispanics (19.14%) and whites (12.26%), (P<.01). Multivariate logistic regression analyses indicated that physical inactivity, lower educational levels, smoking, daily consumption of vegetables and/or fruits <3 servings, and lack of social support were significantly associated with the odds of having CMS. In conclusion, black and Hispanic adults have a significantly higher prevalence of CMS than whites. The significant association between CMS and risk factors provides new insights in the direction of health promotion to prevent and control CMS in those who are at high risk.

  11. The mitochondrial gene orfH79 plays a critical role in impairing both male gametophyte development and root growth in CMS-Honglian rice.

    PubMed

    Peng, Xiaojue; Wang, Kun; Hu, Chaofeng; Zhu, Youlin; Wang, Ting; Yang, Jing; Tong, Jiping; Li, Shaoqing; Zhu, Yingguo

    2010-06-24

    Cytoplasmic male sterility (CMS) has often been associated with abnormal mitochondrial open reading frames. The mitochondrial gene orfH79 is a candidate gene for causing the CMS trait in CMS-Honglian (CMS-HL) rice. However, whether the orfH79 expression can actually induce CMS in rice remains unclear. Western blot analysis revealed that the ORFH79 protein is mainly present in mitochondria of CMS-HL rice and is absent in the fertile line. To investigate the function of ORFH79 protein in mitochondria, this gene was fused to a mitochondrial transit peptide sequence and used to transform wild type rice, where its expression induced the gametophytic male sterile phenotype. In addition, excessive accumulation of reactive oxygen species (ROS) in the microspore, a reduced ATP/ADP ratio, decreased mitochondrial membrane potential and a lower respiration rate in the transgenic plants were found to be similar to those in CMS-HL rice. Moreover, retarded growth of primary and lateral roots accompanied by abnormal accumulation of ROS in the root tip was observed in both transgenic rice and CMS-HL rice (YTA). These results suggest that the expression of orfH79 in mitochondria impairs mitochondrial function, which affects the development of both male gametophytes and the roots of CMS-HL rice.

  12. CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

    PubMed

    Pilati, C; Taieb, J; Balogoun, R; Marisa, L; de Reyniès, A; Laurent-Puig, P

    2017-05-01

    Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease

    PubMed Central

    Azad, Priti; Zhao, Huiwen W.; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Hsiao, Yu Hsin; Bafna, Vineet

    2016-01-01

    In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge’s disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. PMID:27821551

  14. Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease.

    PubMed

    Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Appenzeller, Otto; Hsiao, Yu Hsin; Bafna, Vineet; Haddad, Gabriel G

    2016-11-14

    In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. © 2016 Azad et al.

  15. Enabling opportunistic resources for CMS Computing Operations

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

    Hufnagel, Dirk

    With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize opportunistic resources resources not owned by, or a priori configured for CMS to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are used to enablemore » access and bring the CMS environment into these non CMS resources. Finally, we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

  16. Enabling opportunistic resources for CMS Computing Operations

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

    Hufnagel, Dick

    With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize “opportunistic” resources — resources not owned by, or a priori configured for CMS — to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are usedmore » to enable access and bring the CMS environment into these non CMS resources. Here we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

  17. Enabling opportunistic resources for CMS Computing Operations

    DOE PAGES

    Hufnagel, Dirk

    2015-12-23

    With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize opportunistic resources resources not owned by, or a priori configured for CMS to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are used to enablemore » access and bring the CMS environment into these non CMS resources. Finally, we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

  18. [Recognition of psychiatric disorders with a religious content by members of the clergy of different denominations in the Netherlands].

    PubMed

    Noort, A; Braam, A W; van Gool, A R; Verhagen, P J; Beekman, A T F

    2012-01-01

    Clergy members (CMS) frequently provide support and counselling for people with psychological and psychiatric disorders. There is evidence in the literature that CMS consider themselves to be inadequately trained to recognise psychiatric disorders. To investigate to what extent CMS are able to recognise psychiatric symptoms. CMS were recruited in the south-west of the Netherlands among various denominations (Roman Catholic, strict (orthodox) Protestant, moderate Protestant and Evangelical; n = 143) by means of a regional sampling method. The participating CMS (n = 143) and a control group consisting of mental health care professionals MPHS; n = 73) evaluated four vignettes of psychiatric problems with a religious content: two were about a psychiatric disorder (a psychotic state and a psychotic depression/melancholic state), and two concerned non-psychiatric states (a spiritual/religious experience and a mourning reaction with a religious dilemma). For each vignette the respondents scored the suitability of psychiatric medication, the desirability of mental health care, the severity of the disorder and whether there was a religious or spiritual aetiology. Some CMS were able to recognise psychiatric problems almost as well as the MHPS, but among the CMS the degree of recognition varied according to the denomination. Recognition was relatively poor among Evangelical CMS, but was best among the strict Protestant CMS. Evangelical pastors and strict Protestant CMS tended to interpret the non-psychiatric states as pathological. The findings of this study emphasise the need for collaboration between MHPS and CMS and stress the importance of consultation.

  19. 78 FR 56710 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... the following transmissions: OMB, Office of Information and Regulatory Affairs Attention: CMS Desk... Identifiers: CMS-10199 and CMS-10266] Agency Information Collection Activities: Submission for OMB Review... an opportunity for the public to comment on CMS' intention to collect information from the public...

  20. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: (1) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before... organization; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

  1. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: (1) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before... organization; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

  2. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before the intended...; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

  3. 42 CFR 401.108 - CMS rulings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false CMS rulings. 401.108 Section 401.108 Public Health... GENERAL ADMINISTRATIVE REQUIREMENTS Confidentiality and Disclosure § 401.108 CMS rulings. (a) After... regulations, but which has been adopted by CMS as having precedent, may be published in the Federal Register...

  4. 45 CFR 150.319 - Determining the amount of the penalty-mitigating circumstances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement... guidelines for taking into account the factors listed in § 150.317, CMS considers the following: (a) Record... noncompliance without notice from CMS and voluntarily reported that noncompliance, provided that the responsible...

  5. 42 CFR 401.625 - Effect of CMS claims collection decisions on appeals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Effect of CMS claims collection decisions on... Compromise § 401.625 Effect of CMS claims collection decisions on appeals. Any action taken under this..., is not an initial determination for purposes of CMS appeal procedures. ...

  6. 42 CFR 403.248 - Administrative review of CMS determinations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Administrative review of CMS determinations. 403... Certification Program: General Provisions § 403.248 Administrative review of CMS determinations. (a) This section provides for administrative review if CMS determines— (1) Not to certify a policy; or (2) That a...

  7. 78 FR 67149 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Identifier: CMS-R-216] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY... & Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect... accepting comments. 2. By regular mail. You may mail written comments to the following address: CMS, Office...

  8. How Patronage Politics Undermines Parental Participation and Accountability: Community-Managed Schools in Honduras and Guatemala

    ERIC Educational Resources Information Center

    Altschuler, Daniel

    2013-01-01

    This article shows how patronage politics affects a popular international education model: community-managed schools (CMS). Focusing on Honduras's CMS initiative, PROHECO (Programa Hondureno de Educacion Comunitaria), I demonstrate how patronage can undermine CMS accountability. Whereas supporters argue that CMS increases accountability, partisan…

  9. 42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

  10. 42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

  11. 42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

  12. 42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

  13. 42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

  14. [Preparation of vanilline cross-linked rhBMP-2/chitosan microspheres and its effect on mesenchymal stem cells].

    PubMed

    Wu, Gui; Wang, Hai; Qiu, Guixing; Yu, Xin; Su, Xinlin; Ma, Pei; Yin, Bo; Wu, Zhihong

    2015-06-02

    To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 ± 0.07 vs 0.73 ± 0.05, P > 0.05; 48 h:1.19 ± 0.11 vs 1.27 ± 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP-2 was 216.1 ± 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 ± 0.07) and (0.68 ± 0.06) µmol pNPP·min⁻¹·mg⁻¹ protein respectively and both were higher than that of blank culture medium group (0.14 ± 0.01) (P < 0.05). With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive.

  15. Registration of cytoplasmic male-sterile oilseed sunflower genetic stocks CMS GIG2 and CMS GIG2-RV, and fertility restoration lines RF GIG2-MAX 1631 and RF GIG2-MAX 1631-RV

    USDA-ARS?s Scientific Manuscript database

    Two cytoplasmic male-sterile (CMS) oilseed sunflower (Helianthus annuus L.) genetic stocks, CMS GIG2 (Reg. No. xxx, PI xxxx), and CMS GIG2-RV (Reg. No. xxx, PI xxxx), and corresponding fertility restoration lines RF GIG2-MAX 1631 (Reg. No. xxx, PI xxxx) and RF GIG2-MAX 1631-RV (Reg. No. xxx, PI xxx...

  16. CMS Nonpayment Policy, Quality Improvement, and Hospital-Acquired Conditions: An Integrative Review.

    PubMed

    Bae, Sung-Heui

    This integrative review synthesized evidence on the consequences of the Centers for Medicare & Medicaid Services (CMS) nonpayment policy on quality improvement initiatives and hospital-acquired conditions. Fourteen articles were included. This review presents strong evidence that the CMS policy has spurred quality improvement initiatives; however, the relationships between the CMS policy and hospital-acquired conditions are inconclusive. In future research, a comprehensive model of implementation of the CMS nonpayment policy would help us understand the effectiveness of this policy.

  17. CMS Centres Worldwide - a New Collaborative Infrastructure

    NASA Astrophysics Data System (ADS)

    Taylor, Lucas

    2011-12-01

    The CMS Experiment at the LHC has established a network of more than fifty inter-connected "CMS Centres" at CERN and in institutes in the Americas, Asia, Australasia, and Europe. These facilities are used by people doing CMS detector and computing grid operations, remote shifts, data quality monitoring and analysis, as well as education and outreach. We present the computing, software, and collaborative tools and videoconferencing systems. These include permanently running "telepresence" video links (hardware-based H.323, EVO and Vidyo), Webcasts, and generic Web tools such as CMS-TV for broadcasting live monitoring and outreach information. Being Web-based and experiment-independent, these systems could easily be extended to other organizations. We describe the experiences of using CMS Centres Worldwide in the CMS data-taking operations as well as for major media events with several hundred TV channels, radio stations, and many more press journalists simultaneously around the world.

  18. Relations between the Test of Variables of Attention (TOVA) and the Children's Memory Scale (CMS).

    PubMed

    Riccio, Cynthia A; Garland, Beth H; Cohen, Morris J

    2007-09-01

    There is considerable overlap in the constructs of attention and memory. The objective of this study was to examine the relationship between the Test of Variables of Attention (TOVA), a measure of attention, to components of memory and learning as measured by the Children's Memory Scale (CMS). Participants (N = 105) were consecutive referrals to an out-patient facility, generally for learning or behavior problems, who were administered both the TOVA and the CMS. Significant correlations were found between the omissions score on the TOVA and subscales of the CMS. TOVA variability and TOVA reaction time correlated significantly with subscales of the CMS as well. TOVA commission errors did not correlate significantly with any CMS Index. Although significant, the correlation coefficients indicate that the CMS and TOVA are measuring either different constructs or similar constructs but in different ways. As such, both measures may be useful in distinguishing memory from attention problems.

  19. 42 CFR 423.509 - Termination of contract by CMS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan sponsor in writing at least 45... experiences financial difficulties so severe that its ability to make necessary health services available is...) CMS notifies the Part D plan sponsor in writing that its contract will be terminated on a date...

  20. 77 FR 70445 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ...-wide set of credentials and single sign-on capability for multiple CMS applications. In order to prove... and answers); 4. Provide the user a single sign-on, federated CMS EIDM ID and Password; 5... Terms of Service and CMS Privacy Statement on the Web. Form Numbers: CMS-10452 (OCN: 0938-New...

  1. Increasing Honest Responding on Cognitive Distortions in Child Molesters: The Bogus Pipeline Procedure

    ERIC Educational Resources Information Center

    Gannon, Theresa A.

    2006-01-01

    Professionals conclude that child molesters (CMs) hold offense-supportive beliefs (or cognitive distortions) from CMs' questionnaire responses. Because questionnaires are easily faked, we asked 32 CMs to complete a cognitive distortion scale under standard conditions (Time 1). A week later (Time 2), the same CMs completed the scale again. This…

  2. 42 CFR 417.801 - Agreements between CMS and health care prepayment plans.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Agreements between CMS and health care prepayment... CMS and health care prepayment plans. (a) General requirement. (1) In order to participate and receive... written agreement with CMS. (2) An existing group practice prepayment plan (GPPP) that continues as an...

  3. 45 CFR 150.347 - Failure to request a hearing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and....343, CMS may assess the proposed civil money penalty, a less severe penalty, or a more severe penalty. CMS notifies the responsible entity in writing of any penalty that has been assessed and of the means...

  4. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS accepts a request. 411.379 Section 411.379... Physicians and Entities Furnishing Designated Health Services § 411.379 When CMS accepts a request. (a) Upon receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether the...

  5. 42 CFR 405.1834 - CMS reviewing official procedure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false CMS reviewing official procedure. 405.1834 Section... Determinations and Appeals § 405.1834 CMS reviewing official procedure. (a) Scope. A provider that is a party to... Administrator by a designated CMS reviewing official who considers whether the decision of the intermediary...

  6. 42 CFR 457.1003 - CMS review of waiver requests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false CMS review of waiver requests. 457.1003 Section 457.1003 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Waivers: General Provisions § 457.1003 CMS review of waiver requests. CMS will review the waiver requests...

  7. 45 CFR 150.301 - General rule regarding the imposition of civil money penalties.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... to CMS's enforcement authority under § 150.101(b)(2), or any non-Federal governmental plan (or employer that sponsors a non-Federal governmental plan) that is subject to CMS's enforcement authority...

  8. 42 CFR 421.114 - Assignment and reassignment of providers by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Assignment and reassignment of providers by CMS. 421.114 Section 421.114 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH... Assignment and reassignment of providers by CMS. CMS may assign or reassign any provider to any intermediary...

  9. 45 CFR 150.209 - Verification of exhaustion of remedies and contact with State officials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... § 150.209 Verification of exhaustion of remedies and contact with State officials. If CMS receives a complaint or other information indicating that a State is failing to enforce HIPAA requirements, CMS...

  10. Sleep disturbances in long-term immigrants with chronic mountain sickness: a comparison with healthy immigrants at high altitude.

    PubMed

    Guan, Wei; Ga, Qin; Li, Rong; Bai, Zhen-Zhong; Wuren, Tana; Wang, Jin; Yang, Ying-Zhong; Li, Yu-Hong; Ge, Ri-Li

    2015-01-15

    The aim of this study was to examine sleep disturbances in patients with chronic mountain sickness (CMS). The sleep of 14 patients with CMS and 11 healthy controls with or without sleep disorders (control N: without sleep disorders; control D: with sleep disorders) was studied by polysomnography. Hypopnea was the sleep disorder most commonly suffered by CMS patients and control D subjects. No major differences were observed in sleep structure between CMS and control groups, with the exception of shorter rapid eye movement latency in controls and increased deep non-rapid eye movement in the control N group. Periodic breathing was observed in only two study participants, one each in the CMS and control D groups. The level of saturated oxygen was significantly lower in the CMS group during sleep than the control groups (P<0.05). CMS scores were positively correlated with the apnea-hypopnea index, and negatively correlated with saturated oxygen levels. These results demonstrate that sleep disorders and nocturnal hypoxia are important in the development of CMS. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. CMS Analysis School Model

    NASA Astrophysics Data System (ADS)

    Malik, S.; Shipsey, I.; Cavanaugh, R.; Bloom, K.; Chan, Kai-Feng; D'Hondt, J.; Klima, B.; Narain, M.; Palla, F.; Rolandi, G.; Schörner-Sadenius, T.

    2014-06-01

    To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals of CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.

  12. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

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

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less

  13. Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

    PubMed

    Marchand, Sandrine; Bouchene, Salim; de Monte, Michèle; Guilleminault, Laurent; Montharu, Jérôme; Cabrera, Maria; Grégoire, Nicolas; Gobin, Patrice; Diot, Patrice; Couet, William; Vecellio, Laurent

    2015-10-01

    The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

  14. A Population WB-PBPK Model of Colistin and its Prodrug CMS in Pigs: Focus on the Renal Distribution and Excretion.

    PubMed

    Viel, Alexis; Henri, Jérôme; Bouchène, Salim; Laroche, Julian; Rolland, Jean-Guy; Manceau, Jacqueline; Laurentie, Michel; Couet, William; Grégoire, Nicolas

    2018-03-12

    The objective was the development of a whole-body physiologically-based pharmacokinetic (WB-PBPK) model for colistin, and its prodrug colistimethate sodium (CMS), in pigs to explore their tissue distribution, especially in kidneys. Plasma and tissue concentrations of CMS and colistin were measured after systemic administrations of different dosing regimens of CMS in pigs. The WB-PBPK model was developed based on these data according to a non-linear mixed effect approach and using NONMEM software. A detailed sub-model was implemented for kidneys to handle the complex disposition of CMS and colistin within this organ. The WB-PBPK model well captured the kinetic profiles of CMS and colistin in plasma. In kidneys, an accumulation and slow elimination of colistin were observed and well described by the model. Kidneys seemed to have a major role in the elimination processes, through tubular secretion of CMS and intracellular degradation of colistin. Lastly, to illustrate the usefulness of the PBPK model, an estimation of the withdrawal periods after veterinary use of CMS in pigs was made. The WB-PBPK model gives an insight into the renal distribution and elimination of CMS and colistin in pigs; it may be further developed to explore the colistin induced-nephrotoxicity in humans.

  15. The Particle Physics Playground website: tutorials and activities using real experimental data

    NASA Astrophysics Data System (ADS)

    Bellis, Matthew; CMS Collaboration

    2016-03-01

    The CERN Open Data Portal provides access to data from the LHC experiments to anyone with the time and inclination to learn the analysis procedures. The CMS experiment has made a significant amount of data availible in basically the same format the collaboration itself uses, along with software tools and a virtual enviroment in which to run those tools. These same data have also been mined for educational exercises that range from very simple .csv files that can be analyzed in a spreadsheet to more sophisticated formats that use ROOT, a dominant software package in experimental particle physics but not used as much in the general computing community. This talk will present the Particle Physics Playground website (http://particle-physics-playground.github.io/), a project that uses data from the CMS experiment, as well as the older CLEO experiment, in tutorials and exercises aimed at high school and undergraduate students and other science enthusiasts. The data are stored as text files and the users are provided with starter Python/Jupyter notebook programs and accessor functions which can be modified to perform fairly high-level analyses. The status of the project, success stories, and future plans for the website will be presented. This work was supported in part by NSF Grant PHY-1307562.

  16. Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

    PubMed

    Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

    2018-01-01

    Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

  17. Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

    PubMed

    Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

    2018-04-20

    To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

  18. Stability of colistin methanesulfonate in pharmaceutical products and solutions for administration to patients.

    PubMed

    Wallace, Stephanie J; Li, Jian; Rayner, Craig R; Coulthard, Kingsley; Nation, Roger L

    2008-09-01

    Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations. Two commercial CMS formulations were investigated for stability with respect to colistin content, which was measured by a specific high-performance liquid chromatography method. Coly-Mycin M Parenteral (colistimethate lyophilized powder) was stable (<0.1% of CMS present as colistin) for at least 20 weeks at 4 degrees C and 25 degrees C at 60% relative humidity. When Coly-Mycin M was reconstituted with 2 ml of water to a CMS concentration of 200 mg/ml for injection, Coly-Mycin M was stable (<0.1% colistin formed) for at least 7 days at both 4 degrees C and 25 degrees C. When further diluted to 4 mg/ml in a glucose (5%) or saline (0.9%) infusion solution as directed, CMS hydrolyzed faster at 25 degrees C (<4% colistin formed after 48 h) than at 4 degrees C (0.3% colistin formed). The second formulation, CMS Solution for Inhalation (77.5 mg/ml), was stable at 4 degrees C and 25 degrees C for at least 12 months, as determined based on colistin content (<0.1%). This study demonstrated the concentration- and temperature-dependent hydrolysis of CMS. The information provided by this study has important implications for the formulation and clinical use of CMS products.

  19. Evaluation of Flagging Criteria of United States Kidney Transplant Center Performance: How to Best Define Outliers?

    PubMed

    Schold, Jesse D; Miller, Charles M; Henry, Mitchell L; Buccini, Laura D; Flechner, Stuart M; Goldfarb, David A; Poggio, Emilio D; Andreoni, Kenneth A

    2017-06-01

    Scientific Registry of Transplant Recipients report cards of US organ transplant center performance are publicly available and used for quality oversight. Low center performance (LP) evaluations are associated with changes in practice including reduced transplant rates and increased waitlist removals. In 2014, Scientific Registry of Transplant Recipients implemented new Bayesian methodology to evaluate performance which was not adopted by Center for Medicare and Medicaid Services (CMS). In May 2016, CMS altered their performance criteria, reducing the likelihood of LP evaluations. Our aims were to evaluate incidence, survival rates, and volume of LP centers with Bayesian, historical (old-CMS) and new-CMS criteria using 6 consecutive program-specific reports (PSR), January 2013 to July 2015 among adult kidney transplant centers. Bayesian, old-CMS and new-CMS criteria identified 13.4%, 8.3%, and 6.1% LP PSRs, respectively. Over the 3-year period, 31.9% (Bayesian), 23.4% (old-CMS), and 19.8% (new-CMS) of centers had 1 or more LP evaluation. For small centers (<83 transplants/PSR), there were 4-fold additional LP evaluations (52 vs 13 PSRs) for 1-year mortality with Bayesian versus new-CMS criteria. For large centers (>183 transplants/PSR), there were 3-fold additional LP evaluations for 1-year mortality with Bayesian versus new-CMS criteria with median differences in observed and expected patient survival of -1.6% and -2.2%, respectively. A significant proportion of kidney transplant centers are identified as low performing with relatively small survival differences compared with expected. Bayesian criteria have significantly higher flagging rates and new-CMS criteria modestly reduce flagging. Critical appraisal of performance criteria is needed to assess whether quality oversight is meeting intended goals and whether further modifications could reduce risk aversion, more efficiently allocate resources, and increase transplant opportunities.

  20. Substantial Targeting Advantage Achieved by Pulmonary Administration of Colistin Methanesulfonate in a Large-Animal Model

    PubMed Central

    Nguyen, Tri-Hung; Lieu, Linh Thuy; Nguyen, Gary; Bischof, Robert J.; Meeusen, Els N.; Li, Jian; Nation, Roger L.

    2016-01-01

    ABSTRACT Colistin, administered as its inactive prodrug colistin methanesulfonate (CMS), is often used in multidrug-resistant Gram-negative pulmonary infections. The CMS and colistin pharmacokinetics in plasma and epithelial lining fluid (ELF) following intravenous and pulmonary dosing have not been evaluated in a large-animal model with pulmonary architecture similar to that of humans. Six merino sheep (34 to 43 kg body weight) received an intravenous or pulmonary dose of 4 to 8 mg/kg CMS (sodium) or 2 to 3 mg/kg colistin (sulfate) in a 4-way crossover study. Pulmonary dosing was achieved via jet nebulization through an endotracheal tube cuff. CMS and colistin were quantified in plasma and bronchoalveolar lavage fluid (BALF) samples by high-performance liquid chromatography (HPLC). ELF concentrations were calculated via the urea method. CMS and colistin were comodeled in S-ADAPT. Following intravenous CMS or colistin administration, no concentrations were quantifiable in BALF samples. Elimination clearance was 1.97 liters/h (4% interindividual variability) for CMS (other than conversion to colistin) and 1.08 liters/h (25%) for colistin. On average, 18% of a CMS dose was converted to colistin. Following pulmonary delivery, colistin was not quantifiable in plasma and CMS was detected in only one sheep. Average ELF concentrations (standard deviations [SD]) of formed colistin were 400 (243), 384 (187), and 184 (190) mg/liter at 1, 4, and 24 h after pulmonary CMS administration. The population pharmacokinetic model described well CMS and colistin in plasma and ELF following intravenous and pulmonary administration. Pulmonary dosing provided high ELF and low plasma colistin concentrations, representing a substantial targeting advantage over intravenous administration. Predictions from the pharmacokinetic model indicate that sheep are an advantageous model for translational research. PMID:27821445

  1. Underreporting of nursing home utilization on the CMS-2728 in older incident dialysis patients and implications for assessing mortality risk.

    PubMed

    Bowling, C Barrett; Zhang, Rebecca; Franch, Harold; Huang, Yijian; Mirk, Anna; McClellan, William M; Johnson, Theodore M; Kutner, Nancy G

    2015-03-21

    The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported. There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement. The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46 - 1.64) for MDS/2728, 1.48 (1.42 - 1.54) for MDS/No 2728, and 1.38 (1.25 - 1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model. The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.

  2. Characterization and classification of one new cytoplasmic male sterility (CMS) line based on morphological, cytological and molecular markers in non-heading Chinese cabbage (Brassica rapa L.).

    PubMed

    Heng, Shuangping; Shi, Dianyi; Hu, Zhenhua; Huang, Tao; Li, Jinping; Liu, Liyan; Xia, Chunxiu; Yuan, Zhenzhen; Xu, Yuejin; Fu, Tingdong; Wan, Zhengjie

    2015-09-01

    A new non-heading Chinese cabbage CMS line M119A was characterized and specific molecular markers were developed to classify different CMS types. One new non-heading Chinese cabbage (Brassica rapa L.) cytoplasmic male sterile (CMS) line M119A was obtained by interspecific crosses between the recently discovered hau CMS line of Brassica juncea and B. rapa. Furthermore, the line was characterized and compared with other five isonuclear-alloplasmic CMS lines. The M119A line produced six stamens without pollen and only two stamen fused together in fewer flowers. Tissue section indicated that anther abortion in M119A may have occurred during differentiation of the archesporial cells without pollen sac. All the six CMS lines were grouped into three types based on the presence of three PCR fragments of 825, 465 and 772 bp amplified with different mitochondrial genes specific primers. The 825-bp fragment was amplified both in 09-10A and H201A using the specific primer pair P-orf224-atp6, and showed 100 % identity with the mitochondrial gene of pol CMS. The 465-bp fragment was amplified in 30A and 105A using the primer pair P-orf138 and shared 100 % identity with the mitochondrial gene of ogu CMS. The 772-bp fragment was amplified in M119A and H203A using the primer pair P-orf288 and showed 100 % identity with the mitochondrial gene of hau CMS. Therefore, these markers could efficiently distinguish different types of isonuclear-alloplasmic CMS lines of non-heading Chinese cabbage, which were useful for improving the efficiency of cross-breeding and heterosis utilization in cruciferous vegetables.

  3. Stability of Colistin Methanesulfonate in Pharmaceutical Products and Solutions for Administration to Patients▿

    PubMed Central

    Wallace, Stephanie J.; Li, Jian; Rayner, Craig. R.; Coulthard, Kingsley; Nation, Roger L.

    2008-01-01

    Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations. Two commercial CMS formulations were investigated for stability with respect to colistin content, which was measured by a specific high-performance liquid chromatography method. Coly-Mycin M Parenteral (colistimethate lyophilized powder) was stable (<0.1% of CMS present as colistin) for at least 20 weeks at 4°C and 25°C at 60% relative humidity. When Coly-Mycin M was reconstituted with 2 ml of water to a CMS concentration of 200 mg/ml for injection, Coly-Mycin M was stable (<0.1% colistin formed) for at least 7 days at both 4°C and 25°C. When further diluted to 4 mg/ml in a glucose (5%) or saline (0.9%) infusion solution as directed, CMS hydrolyzed faster at 25°C (<4% colistin formed after 48 h) than at 4°C (0.3% colistin formed). The second formulation, CMS Solution for Inhalation (77.5 mg/ml), was stable at 4°C and 25°C for at least 12 months, as determined based on colistin content (<0.1%). This study demonstrated the concentration- and temperature-dependent hydrolysis of CMS. The information provided by this study has important implications for the formulation and clinical use of CMS products. PMID:18606838

  4. Factors affecting pharmacists’ recommendation of complementary medicines – a qualitative pilot study of Australian pharmacists

    PubMed Central

    2012-01-01

    Background Complementary medicines (CMs) are widely used by the Australian public, and pharmacies are major suppliers of these medicines. The integration of CMs into pharmacy practice is well documented, but the behaviours of pharmacists in recommending CMs to customers are less well studied. This study reports on factors that influence whether or not pharmacists in Australia recommend CMs to their customers. Methods Data were collected from semi-structured interviews with twelve practicing pharmacists based in Brisbane, Australia. The qualitative data were analysed by thematic analysis. Results The primary driver of the recommendation of CMs was a desire to provide a health benefit to the customer. Other important drivers were an awareness of evidence of efficacy, customer feedback and pharmacy protocols to recommend a CM alongside a particular pharmaceutical medication. The primary barrier to the recommendation of CMs was safety concerns around patients on multiple medications or with complex health issues. Also, a lack of knowledge of CMs, a perceived lack of evidence or a lack of time to counsel patients were identified as barriers. There was a desire to see a greater integration of CM into formal pharmacy education. Additionally, the provision of good quality educational materials was seen as important to allow pharmacists to assess levels of evidence for CMs and educate them on their safe and appropriate use. Conclusions Pharmacists who frequently recommend CMs identify many potential benefits for patients and see it as an important part of providing a ‘healthcare solution’. To encourage the informed use of CMs in pharmacy there is a need for the development of accessible, quality resources on CMs. In addition, incorporation of CM education into pharmacy curricula would better prepare graduate pharmacists for community practice. Ultimately, such moves would contribute to the safe and effective use of CMs to the benefit of consumers. PMID:23051066

  5. Pharmacokinetics of Chinese medicines: strategies and perspectives.

    PubMed

    Yan, Ru; Yang, Ying; Chen, Yijia

    2018-01-01

    The modernization and internationalization of Chinese medicines (CMs) are hampered by increasing concerns on the safety and the efficacy. Pharmacokinetic (PK) study is indispensable to establish concentration-activity/toxicity relationship and facilitate target identification and new drug discovery from CMs. To cope with tremendous challenges rooted from chemical complexity of CMs, the classic PK strategies have evolved rapidly from PK study focusing on marker/main drug components to PK-PD correlation study adopting metabolomics approaches to characterize associations between disposition of global drug-related components and host metabolic network shifts. However, the majority of PK studies of CMs have adopted the approaches tailored for western medicines and focused on the systemic exposures of drug-related components, most of which were found to be too low to account for the holistic benefits of CMs. With an area under concentration-time curve- or activity-weighted approach, integral PK attempts to understand the PK-PD relevance with the integrated PK profile of multiple co-existing structural analogs (prototyes/metabolites). Cellular PK-PD complements traditional PK-PD when drug targets localize inside the cells, instead of at the surface of cell membrane or extracellular space. Considering the validated clinical benefits of CMs, reverse pharmacology-based reverse PK strategy was proposed to facilitate target identification and new drug discovery. Recently, gut microbiota have demonstrated multifaceted roles in drug efficacy/toxicity. In traditional oral intake, the presystemic interactions of CMs with gut microbiota seem inevitable, which can contribute to the holistic benefits of CMs through biotransforming CMs components, acting as the peripheral target, and regulating host drug disposition. Hence, we propose a global PK-PD approach which includes the presystemic interaction of CMs with gut microbiota and combines omics with physiologically based pharmacokinetic modeling to offer a comprehensive understanding of the PK-PD relationship of CMs. Moreover, validated clinical benefits of CMs and poor translational potential of animal PK data urge more research efforts in human PK study.

  6. Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet

    PubMed Central

    2012-01-01

    Background In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population. Methods We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated. Results Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs. Conclusion The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases. PMID:22672510

  7. Phenomenology of 2HDM with vectorlike quarks

    NASA Astrophysics Data System (ADS)

    Arhrib, A.; Benbrik, R.; King, S. J. D.; Manaut, B.; Moretti, S.; Un, C. S.

    2018-05-01

    In this paper, we examine the consistency of the Large Hadron Collider (LHC) data collected during Runs 1 and 2 by the ATLAS and CMS experiments with the predictions of a 2-Higgs doublet model embedding vectorlike quarks (VLQs) for p p →H , A production and H , A →γ γ decay mechanisms, respectively, of (nearly) degenerate C P -even (H ) and C P -odd (A ) Higgs bosons. We show that a scenario containing one single VLQ with electromagnetic charge 2 /3 can explain the above ATLAS and CMS data for masses in the region 350 GeV ≤mVLQ≤1.5 TeV or so, depending on tan β , and for several values of the mixing angle between the top quark (t ) and its VLQ counterpart (T ). We then perform a global fit onto the model by including all relevant experimental as well as theoretical constraints. The surviving samples of our analysis are discussed within 2 σ of the LHC measurements. Additionally, we also comment on the recent anomalous result reported by CMS using Run 2 data on the associated Standard Model Higgs boson production with top quark pairs p p →t t ¯ h with an observed significance of 3.3 σ . Other than these specific examples, we also present a phenomenological analysis of the main features of the model, including the most promising T decay channels.

  8. A review on III-V core-multishell nanowires: growth, properties, and applications

    NASA Astrophysics Data System (ADS)

    Royo, Miquel; De Luca, Marta; Rurali, Riccardo; Zardo, Ilaria

    2017-04-01

    This review focuses on the emerging field of core-multishell (CMS) semiconductor nanowires (NWs). In these kinds of wires, a NW grown vertically on a substrate acts as a template for the coaxial growth of two or more layers wrapped around it. Thanks to the peculiar geometry, the strain is partially released along the radial direction, thus allowing the creation of fascinating heterostructures, even based on lattice mismatched materials that would hardly grow in a planar geometry. Enabling the unique bridging of the 1D nature of NWs with the exciting properties of 2D heterostructures, these novel systems are becoming attractive for material science, as well as fundamental and applied physics. We will focus on NWs made of III-V and III-V-based alloys as they represent a model system in which present growth techniques have reached a high degree of control on the material structural properties, and many physical properties have been assessed, from both the theoretical and experimental points of view. In particular, we provide an overview on the growth methods and structural properties of CMS NWs, on the modulation doping mechanisms enabled by these heterostructures, on the effects of a magnetic field, and on the phononic and optical properties typical of CMS NWs. Moreover, we review the main technological applications based on these systems, such as optoelectronic and photovoltaic devices.

  9. Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO4 crystals

    NASA Astrophysics Data System (ADS)

    Adams, T.; Adzic, P.; Ahuja, S.; Anderson, D.; Andrews, M. B.; Antropov, I.; Antunovic, Z.; Arcidiacono, R.; Arenton, M. W.; Argirò, S.; Askew, A.; Attikis, A.; Auffray, E.; Baccaro, S.; Baffioni, S.; Bailleux, D.; Baillon, P.; Barney, D.; Barone, L.; Bartoloni, A.; Bartosik, N.; Becheva, E.; Bein, S.; Silva, C. Beirāo Da Cruz E.; Bell, K. W.; Benaglia, A.; Bendavid, J.; Berry, D.; Besancon, M.; Betev, B.; Bialas, W.; Bianchini, L.; Biino, C.; Bitioukov, S.; Bornheim, A.; Brianza, L.; Brinkerhoff, A.; Brown, R. M.; Brummitt, A.; Busson, P.; Candelise, V.; Carrillo Montoya, C. A.; Cartiglia, N.; Cavallari, F.; Chang, Y. W.; Chen, K. F.; Chevenier, G.; Chipaux, R.; Clement, E.; Cockerill, D. J. A.; Corpe, L.; Couderc, F.; Courbon, B.; Cox, B.; Cucciati, G.; Cussans, D.; D'imperio, G.; Da Silva Di Calafiori, D. R.; Dafinei, I.; Daguin, J.; Daskalakis, G.; Tinoco Mendes, A. D.; De Guio, F.; Degano, A.; Dejardin, M.; Del Re, D.; Della Ricca, G.; Denegri, D.; Depasse, P.; Dev, N.; Deyrail, D.; Di Marco, E.; Diamond, B.; Diemoz, M.; Dissertori, G.; Dittmar, M.; Djambazov, L.; Doan, T. H.; Dobrzynski, L.; Dolgopolov, A.; Donegà, M.; Dordevic, M.; Dröge, M.; Durkin, T.; Dutta, D.; El Mamouni, H.; Elliott-Peisert, A.; Elmalis, E.; Fabbro, B.; Fasanella, G.; Faure, J.; Fay, J.; Fedorov, A.; Ferri, F.; Francis, B.; Frank, N.; Franzoni, G.; Funk, W.; Ganjour, S.; Gascon, S.; Gastal, M.; Geerebaert, Y.; Gelli, S.; Gerosa, R.; Ghezzi, A.; Giakoumopoulou, V. A.; Givernaud, A.; Gninenko, S.; Godinovic, N.; Goeckner-Wald, N.; Golubev, N.; Govoni, P.; Gras, P.; Guilloux, F.; Haller, C.; Hamel de Monchenault, G.; Hansen, M.; Hansen, P.; Hardenbrook, J.; Heath, H. F.; Hill, J.; Hirosky, R.; Hobson, P. R.; Holme, O.; Honma, A.; Hou, W.-S.; Hsiung, Y.; Iiyama, Y.; Ille, B.; Ingram, Q.; Jain, S.; Jarry, P.; Jessop, C.; Jovanovic, D.; Kachanov, V.; Kalafut, S.; Kao, K. Y.; Kellams, N.; Kesisoglou, S.; Khatiwada, A.; Konoplyannikov, A.; Konstantinov, D.; Korzhik, M.; Kovac, M.; Kubota, Y.; Kucher, I.; Kumar, A.; Kumar, A.; Kuo, C.; Kyberd, P.; Kyriakis, A.; Latyshev, G.; Lecoq, P.; Ledovskoy, A.; Lei, Y. J.; Lelas, D.; Lethuillier, M.; Li, H.; Lin, W.; Liu, Y. F.; Locci, E.; Longo, E.; Loukas, D.; Lu, R.-S.; Lucchini, M. T.; Lustermann, W.; Mackay, C. K.; Magniette, F.; Malcles, J.; Malhotra, S.; Mandjavidze, I.; Maravin, Y.; Margaroli, F.; Marinelli, N.; Marini, A. C.; Martelli, A.; Marzocchi, B.; Massironi, A.; Matveev, V.; Mechinsky, V.; Meng, F.; Meridiani, P.; Micheli, F.; Milosevic, J.; Mousa, J.; Musella, P.; Nessi-Tedaldi, F.; Neu, C.; Newman, H.; Nicolaou, C.; Nourbakhsh, S.; Obertino, M. M.; Organtini, G.; Orimoto, T.; Paganini, P.; Paganis, E.; Paganoni, M.; Pandolfi, F.; Panov, V.; Paramatti, R.; Parracho, P.; Pastrone, N.; Paulini, M.; Pauss, F.; Pauwels, K.; Pellegrino, F.; Pena, C.; Perniè, L.; Peruzzi, M.; Petrakou, E.; Petyt, D.; Pigazzini, S.; Piroué, P.; Planer, M.; Plestina, R.; Polic, D.; Prosper, H.; Ptochos, F.; Puljak, I.; Quittnat, M.; Ragazzi, S.; Rahatlou, S.; Rander, J.; Ranjan, K.; Rasteiro Da Silva, J.; Razis, P. A.; Romanteau, T.; Rosowsky, A.; Rovelli, C.; Rusack, R.; Salerno, R.; Santanastasio, F.; Santra, A.; Schönenberger, M.; Seez, C.; Sharma, V.; Shepherd-Themistocleous, C.; Shiu, J. G.; Shivpuri, R. K.; Singovsky, A.; Sinthuprasith, T.; Sirois, Y.; Smiljkovic, N.; Soffi, L.; Sun, M.; Symonds, P.; Tabarelli de Fatis, T.; Tambe, N.; Tarasov, I.; Taroni, S.; Teixeira De Lima, R.; Thea, A.; Theofilatos, K.; Thiant, F.; Titov, M.; Torbet, M.; Trapani, P. P.; Tropea, P.; Tsai, J. f.; Tsirou, A.; Turkewitz, J.; Tyurin, N.; Tzeng, Y. M.; Uzunian, A.; Valls, N.; Varela, J.; Veeraraghavan, V.; Verdini, P. G.; Vichoudis, P.; Vlassov, E.; Wang, J.; Wang, T.; Weinberg, M.; Wolfe, E.; Wood, J.; Zabi, A.; Zahid, S.; Zelepoukine, S.; Zghiche, A.; Zhang, L.; Zhu, K.; Zhu, R.; Zuyeuski, R.

    2016-04-01

    The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1× 1013 and 1.3× 1014 cm-2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb-1 and 3000 fb-1 respectively, corresponding to the end of the LHC and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. The experimental results obtained can be used to estimate the long term performance of the CMS ECAL.

  10. 42 CFR 423.509 - Termination of contract by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan in writing 90 days before the... difficulties so severe that its ability to make necessary health services available is impaired to the point of... writing that its contract will be terminated on a date specified by CMS. If a termination in is effective...

  11. 42 CFR 423.509 - Termination of contract by CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan in writing 90 days before the... difficulties so severe that its ability to make necessary health services available is impaired to the point of... writing that its contract will be terminated on a date specified by CMS. If a termination in is effective...

  12. 42 CFR 423.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Collection of civil money penalties imposed by CMS... BENEFIT Intermediate Sanctions § 423.758 Collection of civil money penalties imposed by CMS. (a) When a Part D plan sponsor does not request a hearing CMS initiates collection of the civil money penalty...

  13. 42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Collection of civil money penalties imposed by CMS... Sanctions § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

  14. 42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Collection of civil money penalties imposed by CMS... § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

  15. 42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Collection of civil money penalties imposed by CMS... Sanctions § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

  16. 45 CFR 150.303 - Basis for initiating an investigation of a potential violation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... may be failing to meet an applicable HIPAA requirement, may warrant an investigation. CMS may consider... acting on that individual's behalf, may file a complaint with CMS if he or she believes that a right to...

  17. 42 CFR 433.320 - Procedures for refunds to CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for refunds to CMS. 433.320 Section 433... Overpayments to Providers § 433.320 Procedures for refunds to CMS. (a) Basic requirements. (1) The agency must refund the Federal share of overpayments that are subject to recovery to CMS through a credit on its...

  18. 42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Collection of civil money penalties imposed by CMS... § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

  19. 42 CFR 447.256 - Procedures for CMS action on assurances and State plan amendments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for CMS action on assurances and State... for Inpatient Hospital and Long-Term Care Facility Services Payment Rates § 447.256 Procedures for CMS action on assurances and State plan amendments. (a) Criteria for approval. (1) CMS approval action on...

  20. 42 CFR 438.730 - Sanction by CMS: Special rules for MCOs

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Sanction by CMS: Special rules for MCOs 438.730... SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Sanctions § 438.730 Sanction by CMS: Special rules for MCOs (a) Basis for sanction. (1) A State agency may recommend that CMS impose the denial of...

  1. 42 CFR 411.380 - When CMS issues a formal advisory opinion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS issues a formal advisory opinion. 411.380... Relationships Between Physicians and Entities Furnishing Designated Health Services § 411.380 When CMS issues a formal advisory opinion. (a) CMS considers an advisory opinion to be issued once it has received payment...

  2. 42 CFR 426.515 - CMS' role in making the NCD record available.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' role in making the NCD record available. 426.515 Section 426.515 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND... COVERAGE DETERMINATIONS Review of an NCD § 426.515 CMS' role in making the NCD record available. CMS will...

  3. 42 CFR 423.758 - Collection of civil money penalties imposed by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Collection of civil money penalties imposed by CMS... Intermediate Sanctions § 423.758 Collection of civil money penalties imposed by CMS. (a) When a Part D plan sponsor does not request a hearing CMS initiates collection of the civil money penalty following the...

  4. 40 CFR Appendix A to Subpart Ll of... - Applicability of General Provisions

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... not require CMS or CMS performance evaluation. 63.8(e) Performance evaluation for CMS No 63.9(b)(1)-(5... evaluations No Subpart LL does not require performance evaluation for CMS. 63.11(a)-(b) Control device... Appendix A to Subpart LL of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  5. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes.

    PubMed

    Veroniki, Areti Angeliki; Cogo, Elise; Rios, Patricia; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

    2017-05-05

    Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes). After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not. The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control. PROSPERO CRD42014008925.

  6. Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

    2017-06-15

    Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

  7. Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

    PubMed

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

    2014-12-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and Intravenous Administration of CMS in Critically Ill Patients

    PubMed Central

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Mimoz, Olivier

    2014-01-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. PMID:25267660

  9. Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness.

    PubMed

    Ge, R L; Shai, H R; Takeoka, M; Hanaoka, M; Koizumi, T; Matsuzawa, Y; Kubo, K; Kobayashi, T

    2001-01-01

    Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

  10. Treadmill exercise alleviates chronic mild stress-induced depression in rats.

    PubMed

    Lee, Taeck-Hyun; Kim, Kijeong; Shin, Mal-Soon; Kim, Chang-Ju; Lim, Baek-Vin

    2015-12-01

    Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2'-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression.

  11. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. 42 CFR 416.30 - Terms of agreement with CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Terms of agreement with CMS. 416.30 Section 416.30... of agreement with CMS. As part of the agreement under § 416.26 the ASC must agree to the following... in subpart C of this part and to report promptly to CMS any failure to do so. (b) Limitation on...

  13. Evaluation of Using Course-Management Software: Supplementing a Course that Requires a Group Research Project

    ERIC Educational Resources Information Center

    Korchmaros, Josephine D.; Gump, Nathaniel W.

    2009-01-01

    The benefits of course-management software (CMS) will not be realized if it is underused. The authors investigated one possible barrier to CMS use, students' perceptions of using CMS. After taking a course requiring a group research project, college students reported their perceptions of the use of CMS for the course. Overall, students did not…

  14. Recent Highlights of Metabolomics in Chinese Medicine Syndrome Research

    PubMed Central

    Zhang, Ai-hua; Sun, Hui; Qiu, Shi; Wang, Xi-jun

    2013-01-01

    Chinese medicine syndrome (CMS, “ZHENG” in Chinese) is an understanding of the regularity of disease occurrence and development as well as a certain stage of a comprehensive response of patients with body condition. However, because of the complexity of CMS and the limitation of present investigation method, the research for deciphering the scientific basis and systematic features of CMS is difficult to go further. Metabolomics enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers. Moreover, its method and design resemble those of traditional Chinese medicine (TCM) which focuses on human disease via the integrity of close relationship between body and syndromes. In the systemic context, metabolomics has a convergence with TCM syndrome; therefore it could provide useful tools for exploring essence of CMS disease, facilitating personalized TCM, and will help to in-depth understand CMS. The integration of the metabolomics and CMS aspects will give promise to bridge the gap between Chinese and Western medicine and help catch the traditional features of CMS. In this paper, particular attention will be paid to the past successes in applications of robust metabolomic approaches to contribute to low-molecular-weight metabolites (biomarkers) discovery in CMS research and development. PMID:24302964

  15. IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes

    PubMed Central

    Vaidyanathan, Ravi; Markandeya, Yogananda S.; Kamp, Timothy J.; Makielski, Jonathan C.; January, Craig T.

    2016-01-01

    Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately −80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms. PMID:27059077

  16. CMS Analysis School Model

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

    Malik, S.; Shipsey, I.; Cavanaugh, R.

    To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals ofmore » CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.« less

  17. Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes.

    PubMed

    Horváth, András; Lemoine, Marc D; Löser, Alexandra; Mannhardt, Ingra; Flenner, Frederik; Uzun, Ahmet Umur; Neuber, Christiane; Breckwoldt, Kaja; Hansen, Arne; Girdauskas, Evaldas; Reichenspurner, Hermann; Willems, Stephan; Jost, Norbert; Wettwer, Erich; Eschenhagen, Thomas; Christ, Torsten

    2018-03-13

    Human induced pluripotent stem cell (hiPSC) cardiomyocytes (CMs) show less negative resting membrane potential (RMP), which is attributed to small inward rectifier currents (I K1 ). Here, I K1 was measured in hiPSC-CMs (proprietary and commercial cell line) cultured as monolayer (ML) or 3D engineered heart tissue (EHT) and, for direct comparison, in CMs from human right atrial (RA) and left ventricular (LV) tissue. RMP was measured in isolated cells and intact tissues. I K1 density in ML- and EHT-CMs from the proprietary line was similar to LV and RA, respectively. I K1 density in EHT-CMs from the commercial line was 2-fold smaller than in the proprietary line. RMP in EHT of both lines was similar to RA and LV. Repolarization fraction and I K,ACh response discriminated best between RA and LV and indicated predominantly ventricular phenotype in hiPSC-CMs/EHT. The data indicate that I K1 is not necessarily low in hiPSC-CMs, and technical issues may underlie low RMP in hiPSC-CMs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Cerebral cavernous malformations: natural history and clinical management.

    PubMed

    Gross, Bradley A; Du, Rose

    2015-01-01

    Cavernous malformations (CMs) are angiographically-occult clusters of dilated sinusoidal channels that may present clinically with seizures, focal neurological deficits and/or hemorrhage. Across natural history studies, the annual hemorrhage rate ranged from 1.6-3.1% per patient-year, decreasing to 0.08-0.2% per patient-year for incidental CMs and to 0.3-0.6% for the collective group of unruptured CMs. Prior hemorrhage is a significant risk factor for subsequent CM hemorrhage. Hemorrhage clustering, particularly within the first 2 years, is an established phenomenon that may confound results of natural history studies evaluating the rate of rehemorrhage. Indeed, rehemorrhage rates for hemorrhagic CMs range from 4.5-22.9% in the literature. Surgical resection is the gold standard treatment for surgically-accessible, symptomatic CMs. Incidental CMs or minimally symptomatic, surgically inaccessible eloquent lesions may be considered for observation. Stereotactic radiosurgery is a controversial treatment approach of consideration only for cases of highly aggressive, surgically inaccessible CMs.

  19. The CMS dataset bookkeeping service

    NASA Astrophysics Data System (ADS)

    Afaq, A.; Dolgert, A.; Guo, Y.; Jones, C.; Kosyakov, S.; Kuznetsov, V.; Lueking, L.; Riley, D.; Sekhri, V.

    2008-07-01

    The CMS Dataset Bookkeeping Service (DBS) has been developed to catalog all CMS event data from Monte Carlo and Detector sources. It provides the ability to identify MC or trigger source, track data provenance, construct datasets for analysis, and discover interesting data. CMS requires processing and analysis activities at various service levels and the DBS system provides support for localized processing or private analysis, as well as global access for CMS users at large. Catalog entries can be moved among the various service levels with a simple set of migration tools, thus forming a loose federation of databases. DBS is available to CMS users via a Python API, Command Line, and a Discovery web page interfaces. The system is built as a multi-tier web application with Java servlets running under Tomcat, with connections via JDBC to Oracle or MySQL database backends. Clients connect to the service through HTTP or HTTPS with authentication provided by GRID certificates and authorization through VOMS. DBS is an integral part of the overall CMS Data Management and Workflow Management systems.

  20. Influence of off-stoichiometry on magnetoresistance characteristics of Co2MnSi/Ag-based current-perpendicular-to-plane spin valves

    NASA Astrophysics Data System (ADS)

    Inoue, Masaki; Hu, Bing; Moges, Kidist; Inubushi, Kazuumi; Nakada, Katsuyuki; Yamamoto, Masafumi; Uemura, Tetsuya

    2017-08-01

    The influence of off-stoichiometry of Co2MnSi (CMS) spin sources on giant magnetoresistance characteristics was investigated for CMS/Ag-based current-perpendicular-to-plane spin valves prepared with various Mn compositions α in Co2MnαSi0.82 electrodes. The magnetoresistance ratio of the prepared CMS/Co50Fe50 (CoFe) (1.1 nm)/Ag/CoFe (1.1)/CMS spin valves systematically increased with α from 11.4% for Mn-deficient α = 0.62 to 20.7% for Mn-rich α = 1.45 at 290 K. This result suggests that increasing α from a Mn-deficient to Mn-rich value increases the spin polarization by suppressing CoMn antisites harmful to the half-metallicity. Thus, our results demonstrate that appropriately controlling the film composition toward a Mn-rich one is highly effective for enhancing the half-metallicity of CMS in CMS-based spin valves, as it is in CMS-based magnetic tunnel junctions.

  1. Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers.

    PubMed

    Li, Junjun; Minami, Itsunari; Yu, Leqian; Tsuji, Kiyotaka; Nakajima, Minako; Qiao, Jing; Suzuki, Masato; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Liu, Li; Chen, Yong

    2016-01-01

    Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays.

  2. Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers

    PubMed Central

    Minami, Itsunari; Yu, Leqian; Nakajima, Minako; Qiao, Jing; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Chen, Yong

    2016-01-01

    Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays. PMID:27446217

  3. Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

    PubMed

    Yan, Junjie; Tian, Han; Wang, Shuzhen; Shao, Jinzhen; Zheng, Yinzhen; Zhang, Hongyuan; Guo, Lin; Ding, Yi

    2014-08-28

    Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as carbohydrate metabolism, stress response, protein synthesis. To our knowledge, this is the first report using the iTRAQ-labeled quantitative proteomic to study the protein expression variation during the abortion processes between a CMS line and its maintainer line. These results provide new insights on the CMS mechanisms of ZD-CMS rice line. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Physics Goals and Experimental Challenges of the Proton-Proton High-Luminosity Operation of the LHC

    NASA Astrophysics Data System (ADS)

    Campana, P.; Klute, M.; Wells, P. S.

    2016-10-01

    The completion of Run 1 of the Large Hadron Collider (LHC) at CERN has seen the discovery of the Higgs boson and an unprecedented number of precise measurements of the Standard Model, and Run 2 has begun to provide the first data at higher energy. The high-luminosity upgrade of the LHC (HL-LHC) and the four experiments (ATLAS, CMS, ALICE, and LHCb) will exploit the full potential of the collider to discover and explore new physics beyond the Standard Model. We review the experimental challenges and the physics opportunities in proton-proton collisions at the HL-LHC.

  5. 42 CFR 405.1010 - When CMS or its contractors may participate in an ALJ hearing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS or its contractors may participate in an... Hearings § 405.1010 When CMS or its contractors may participate in an ALJ hearing. (a) An ALJ may request, but may not require, CMS and/or one or more of its contractors to participate in any proceedings...

  6. Particle Tracking Model (PTM) with Coastal Modeling System (CMS)

    DTIC Science & Technology

    2015-11-04

    Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The Particle Tracking Model (PTM) is a Lagrangian...currents and waves. The Coastal Inlets Research Program (CIRP) supports the PTM with the Coastal Modeling System ( CMS ), which provides coupled wave...and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a GUI environment for input development

  7. Challenges to Software/Computing for Experimentation at the LHC

    NASA Astrophysics Data System (ADS)

    Banerjee, Sunanda

    The demands of future high energy physics experiments towards software and computing have led the experiments to plan the related activities as a full-fledged project and to investigate new methodologies and languages to meet the challenges. The paths taken by the four LHC experiments ALICE, ATLAS, CMS and LHCb are coherently put together in an LHC-wide framework based on Grid technology. The current status and understandings have been broadly outlined.

  8. Identification of mitochondrial DNA sequence variation and development of single nucleotide polymorphic markers for CMS-D8 in cotton.

    PubMed

    Suzuki, Hideaki; Yu, Jiwen; Wang, Fei; Zhang, Jinfa

    2013-06-01

    Cytoplasmic male sterility (CMS), which is a maternally inherited trait and controlled by novel chimeric genes in the mitochondrial genome, plays a pivotal role in the production of hybrid seed. In cotton, no PCR-based marker has been developed to discriminate CMS-D8 (from Gossypium trilobum) from its normal Upland cotton (AD1, Gossypium hirsutum) cytoplasm. The objective of the current study was to develop PCR-based single nucleotide polymorphic (SNP) markers from mitochondrial genes for the CMS-D8 cytoplasm. DNA sequence variation in mitochondrial genes involved in the oxidative phosphorylation chain including ATP synthase subunit 1, 4, 6, 8 and 9, and cytochrome c oxidase 1, 2 and 3 subunits were identified by comparing CMS-D8, its isogenic maintainer and restorer lines on the same nuclear genetic background. An allelic specific PCR (AS-PCR) was utilized for SNP typing by incorporating artificial mismatched nucleotides into the third or fourth base from the 3' terminus in both the specific and nonspecific primers. The result indicated that the method modifying allele-specific primers was successful in obtaining eight SNP markers out of eight SNPs using eight primer pairs to discriminate two alleles between AD1 and CMS-D8 cytoplasms. Two of the SNPs for atp1 and cox1 could also be used in combination to discriminate between CMS-D8 and CMS-D2 cytoplasms. Additionally, a PCR-based marker from a nine nucleotide insertion-deletion (InDel) sequence (AATTGTTTT) at the 59-67 bp positions from the start codon of atp6, which is present in the CMS and restorer lines with the D8 cytoplasm but absent in the maintainer line with the AD1 cytoplasm, was also developed. A SNP marker for two nucleotide substitutions (AA in AD1 cytoplasm to CT in CMS-D8 cytoplasm) in the intron (1,506 bp) of cox2 gene was also developed. These PCR-based SNP markers should be useful in discriminating CMS-D8 and AD1 cytoplasms, or those with CMS-D2 cytoplasm as a rapid, simple, inexpensive, and reliable genotyping tool to assist hybrid cotton breeding.

  9. CMS-dependent prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer.

    PubMed

    Smeby, J; Sveen, A; Merok, M A; Danielsen, S A; Eilertsen, I A; Guren, M G; Dienstmann, R; Nesbakken, A; Lothe, R A

    2018-05-01

    The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMSs) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600). A subset was analyzed for gene expression and confident CMS classification was obtained for 317 samples. This cohort was expanded with clinical and molecular data, including CMS classification, from 514 patients in the publically available dataset GSE39582. Gene expression signatures associated with KRAS and BRAFV600E mutations were used to evaluate differential impact of mutations on gene expression among the CMS groups. BRAFV600E and KRAS mutations were both associated with inferior 5-year overall survival (OS) exclusively in MSS tumors (BRAFV600E mutation versus KRAS/BRAF wild-type: Hazard ratio (HR) 2.85, P < 0.001; KRAS mutation versus KRAS/BRAF wild-type: HR 1.30, P = 0.013). BRAFV600E-mutated MSS tumors were strongly enriched and associated with metastatic disease in CMS1, leading to negative prognostic impact in this subtype (OS: BRAFV600E mutation versus wild-type: HR 7.73, P = 0.001). In contrast, the poor prognosis of KRAS mutations was limited to MSS tumors with CMS2/CMS3 epithelial-like gene expression profiles (OS: KRAS mutation versus wild-type: HR 1.51, P = 0.011). The subtype-specific prognostic associations were substantiated by differential effects of BRAFV600E and KRAS mutations on gene expression signatures according to the MSI status and CMS group. BRAFV600E mutations are enriched and associated with metastatic disease in CMS1 MSS tumors, leading to poor prognosis in this subtype. KRAS mutations are associated with adverse outcome in epithelial (CMS2/CMS3) MSS tumors.

  10. Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing

    PubMed Central

    Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A.; Alves, Paula M.

    2016-01-01

    To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. Significance The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. PMID:27025693

  11. Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing.

    PubMed

    Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A; Serra, Margarida; Alves, Paula M

    2016-05-01

    To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. ©AlphaMed Press.

  12. 45 CFR 150.213 - Form and content of notice.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

  13. 45 CFR 150.213 - Form and content of notice.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

  14. Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats.

    PubMed

    Martín-Hernández, David; Tendilla-Beltrán, Hiram; Madrigal, José L M; García-Bueno, Borja; Leza, Juan C; Caso, Javier R

    2018-05-03

    Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs. The expression of elements of the IDO pathway, including kynurenine metabolites, and their possible modulation by ADs was studied in the frontal cortex (FC). CMS increased IDO expression in FC compared to control group, and ADs restored the IDO expression levels to control values. CMS-induced IDO expression led to increased levels of the excitotoxic quinolinic acid (QUINA) compared to control, and ADs prevented the rise in such levels. Neither CMS nor ADs changed significantly the antiexcitotoxic kynurenic acid (KYNA) levels. The QUINA/KYNA ratio, calculated as excitotoxicity risk indicator, increased after CMS and ADs prevented this increase. CMS lowered excitatory amino acid transporter (EAAT)-1 and EAAT-4 expression, and some ADs restored their expression levels. Furthermore, CMS decreased N-methyl-D-aspartate receptor (NMDAR)-2A and 2B protein expression, and ADs mitigated this decrease. Our research examines the link between CMS-induced pro-inflammatory cytokines and the kynurenine pathway; it shows that CMS alters the kynurenine pathway in rat FC. Importantly, it also reveals the ability of classic ADs to prevent potentially harmful situations related to the brain scenario caused by CMS.

  15. Post-operative paediatric cerebellar mutism syndrome: time to move beyond structural MRI.

    PubMed

    Toescu, Sebastian M; Hettige, Samantha; Phipps, Kim; Smith, R J Paul; Haffenden, Verity; Clark, Chris; Hayward, Richard; Mankad, Kshitij; Aquilina, Kristian

    2018-06-20

    To determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma. Retrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Great Ormond Street Hospital between 2003 and 2013. The diagnosis of pCMS was established through a scoring system incorporating mutism, ataxia, behavioural disturbance and cranial nerve deficits. MRI scans performed at three time points were assessed by neuroradiologists blinded to the diagnosis of pCMS. Of 56 children included, 12 (21.4%) developed pCMS as judged by a core symptom of mutism. pCMS was more common in those aged 5 or younger. There was no statistically significant difference in pre-operative distortion or signal change of the dentate or red nuclei or superior cerebellar peduncles (SCPs) between those who did and did not develop pCMS. In both early (median 5 days) and late (median 31 months) post-operative scans, T2-weighted signal change in SCPs was more common in the pCMS group (p = 0.040 and 0.046 respectively). Late scans also showed statistically significant signal change in the dentate nuclei (p = 0.024). The development of pCMS could not be linked to any observable changes on pre-operative structural MRI scans. Post-operative T2-weighted signal change in the SCPs and dentate nuclei underlines the role of cerebellar efferent injury in pCMS. Further research using advanced quantitative MRI sequences is warranted given the inability of conventional pre-surgical MRI to predict pCMS.

  16. Transcriptome analysis of cytoplasmic male sterility and restoration in CMS-D8 cotton.

    PubMed

    Suzuki, Hideaki; Rodriguez-Uribe, Laura; Xu, Jiannong; Zhang, Jinfa

    2013-10-01

    A global view of differential expression of genes in CMS-D8 of cotton was presented in this study which will facilitate the understanding of cytoplasmic male sterility in cotton. Cytoplasmic male sterility (CMS) is a maternally inherited trait in higher plants which is incapable of producing functional pollen. However, the male fertility can be restored by one or more nuclear-encoded restorer genes. A genome-wide transcriptome analysis of CMS and restoration in cotton is currently lacking. In this study, Affymetrix GeneChips© Cotton Genome Array containing 24,132 transcripts was used to compare differentially expressed (DE) genes of flower buds at the meiosis stage between CMS and its restorer cotton plants conditioned by the D8 cytoplasm. A total of 458 (1.9 %) of DE genes including 127 up-regulated and 331 down-regulated ones were identified in the CMS-D8 line. Quantitative RT-PCR was used to validate 10 DE genes selected from seven functional categories. The most frequent DE gene group was found to encode putative proteins involved in cell wall expansion, such as pectinesterase, pectate lyase, pectin methylesterase, glyoxal oxidase, polygalacturonase, indole-3-acetic acid-amino synthetase, and xyloglucan endo-transglycosylase. Genes in cytoskeleton category including actin, which plays a key role in cell wall expansion, cell elongation and cell division, were also highly differentially expressed between the fertile and CMS plants. This work represents the first study in utilizing microarray to identify CMS-related genes by comparing overall DE genes between fertile and CMS plants in cotton. The results provide evidence that many CMS-associated genes are mainly involved in cell wall expansion. Further analysis will be required to elucidate the molecular mechanisms of male sterility which will facilitate the development of new hybrid cultivars in cotton.

  17. Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.

    PubMed

    Durmus, Hacer; Shen, Xin-Ming; Serdaroglu-Oflazer, Piraye; Kara, Bulent; Parman-Gulsen, Yesim; Ozdemir, Coskun; Brengman, Joan; Deymeer, Feza; Engel, Andrew G

    2018-04-01

    Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Median follow-up time was 9.8 years (range 1-22 years). The most common CMS was primary acetylcholine receptor (AChR) deficiency (31/51) and the most common mutations in AChR were c.1219 + 2T > G (12/51) and c.1327delG (6/51) in CHRNE. Four of our 5 kinships with AChE deficiency carried p.W148X that truncates the collagen domain of COLQ, and was previously reported only in patients from Turkey. These were followed by GFPT1 deficiency (4/51), DOK7 deficiency (3/51), slow channel CMS (3/51), fast channel CMS (3/51), choline acetyltransferase deficiency (1/51) and a CMS associated with desmin deficiency (1/51). Distribution of muscle weakness was sometimes useful in giving a clue to the CMS subtype. Presence of repetitive compound muscle action potentials pointed to AChE deficiency or slow channel CMS. Our experience confirms that one needs to be cautious using pyridostigmine, since it can worsen some types of CMS. Ephedrine/salbutamol were very effective in AChE and DOK7 deficiencies and were useful as adjuncts in other types of CMS. Long follow-up gave us a chance to assess progression of the disease, and to witness 12 mainly uneventful pregnancies in 8 patients. In this study, we describe some new phenotypes and detail the clinical features of the well-known CMS. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Purification of Cardiomyocytes from Differentiating Pluripotent Stem Cells using Molecular Beacons Targeting Cardiomyocyte-Specific mRNA

    PubMed Central

    Kim, Sangsung; Park, Hun-Jun; Byun, Jaemin; Cho, Kyu-Won; Saafir, Talib; Song, Ming-Ke; Yu, Shan Ping; Wagner, Mary; Bao, Gang; Yoon, Young-Sup

    2013-01-01

    Background While methods for generating cardiomyocytes (CMs) from pluripotent stem cells (PSCs) have been reported, current methods produce heterogeneous mixtures of CMs and non-CM cells. Here, we report an entirely novel system in which PSC-derived CMs are purified by CM-specific molecular beacons (MBs). MBs are nano-scale probes that emit a fluorescence signal when hybridized to target mRNAs. Method and Results Five MBs targeting mRNAs of either cardiac troponin T or myosin heavy chain 6/7 were generated. Among five MBs, a MB targeting myosin heavy chain 6/7 mRNA (MHC1-MB) identified up to 99% of HL-1 CMs, a mouse CM cell line, but < 3% of four non-CM cell types in flow cytometry analysis, indicating that MHC1-MB is specific for identifying CMs. We delivered MHC1-MB into cardiomyogenically differentiated PSCs through nucleofection. The detection rate of CMs was similar to the percentages of cardiac troponin T (TNNT2) or cardiac troponin I (TNNI3)-positive CMs, supporting the specificity of MBs. Finally, MHC1-MB-positive cells were FACS-sorted from mouse and human PSC differentiating cultures and ~97% cells expressed TNNT2- or TNNI3 determined by flow cytometry. These MB-based sorted cells maintained their CM characteristics verified by spontaneous beating, electrophysiologic studies, and expression of cardiac proteins. When transplanted in a myocardial infarction model, MB-based purified CMs improved cardiac function and demonstrated significant engraftment for 4 weeks without forming tumors. Conclusions We developed a novel CM selection system that allows production of highly purified CMs. These purified CMs and this system can be valuable for cell therapy and drug discovery. PMID:23995537

  19. Reporting trends and outcomes in ST-segment-elevation myocardial infarction national hospital quality assessment programs.

    PubMed

    McCabe, James M; Kennedy, Kevin F; Eisenhauer, Andrew C; Waldman, Howard M; Mort, Elizabeth A; Pomerantsev, Eugene; Resnic, Frederic S; Yeh, Robert W

    2014-01-14

    For patients who undergo primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction, the door-to-balloon time is an important performance measure reported to the Centers for Medicare & Medicaid Services (CMS) and tied to hospital quality assessment and reimbursement. We sought to assess the use and impact of exclusion criteria associated with the CMS measure of door-to-balloon time in primary PCI. All primary PCI-eligible patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) were evaluated for CMS reporting status. Rates of CMS reporting exclusion were the primary end points of interest. Key secondary end points were between-group differences in patient characteristics, door-to-balloon times, and 1-year mortality rates. From 2005 to 2011, 26% (408) of the 1548 primary PCI cases were excluded from CMS reporting. This percentage increased over the study period from 13.9% in 2005 to 36.7% in the first 3 quarters of 2011 (P<0.001). The most frequent cause of exclusion was for a diagnostic dilemma such as a nondiagnostic initial ECG, accounting for 31.2% of excluded patients. Although 95% of CMS-reported cases met door-to-balloon time goals in 2011, this was true of only 61% of CMS-excluded cases and consequently 82.6% of all primary PCI cases performed that year. The 1-year mortality for CMS-excluded patients was double that of CMS-included patients (13.5% versus 6.6%; P<0.001). More than a quarter of patients who underwent primary PCI were excluded from hospital quality reports collected by CMS, and this percentage has grown substantially over time. These findings may have significant implications for our understanding of process improvement in primary PCI and mechanisms for reimbursement through Medicare.

  20. Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa

    PubMed Central

    Bergen, Phillip J.; Li, Jian; Rayner, Craig R.; Nation, Roger L.

    2006-01-01

    There is a dearth of information on the pharmacodynamics of “colistin,” despite its increasing use as a last line of defense for treatment of infections caused by multidrug-resistant gram-negative organisms. The antimicrobial activities of colistin and colistin methanesulfonate (CMS) were investigated by studying the time-kill kinetics of each against a type culture of Pseudomonas aeruginosa in cation-adjusted Mueller-Hinton broth. The appearance of colistin from CMS spiked at 8.0 and 32 mg/liter was measured by high-performance liquid chromatography, which generated colistin concentration-time profiles. These concentration-time profiles were subsequently mimicked in other incubations, independent of CMS, by incrementally spiking colistin. When the cultures were spiked with CMS at either concentration, there was a substantial delay in the onset of the killing effect which was not evident until the concentrations of colistin generated from the hydrolysis of CMS had reached approximately 0.5 to 1 mg/liter (i.e., ∼0.5 to 1 times the MIC for colistin). The time course of the killing effect was similar when colistin was added incrementally to achieve the same colistin concentration-time course observed from the hydrolysis of CMS. Given that the killing kinetics of CMS can be accounted for by the appearance of colistin, CMS is an inactive prodrug of colistin with activity against P. aeruginosa. This is the first study to demonstrate the formation of colistin in microbiological media containing CMS and to demonstrate that CMS is an inactive prodrug of colistin. These findings have important implications for susceptibility testing involving “colistin,” in particular, for MIC measurement and for microbiological assays and pharmacokinetic and pharmacodynamic studies. PMID:16723551

  1. The discovery and measurements of a Higgs boson.

    PubMed

    Gianotti, F; Virdee, T S

    2015-01-13

    In July 2012, the ATLAS and CMS collaborations at CERN's Large Hadron Collider announced the discovery of a Higgs-like boson, a new heavy particle at a mass more than 130 times the mass of a proton. Since then, further data have revealed its properties to be strikingly similar to those of the Standard Model Higgs boson, a particle expected from the mechanism introduced almost 50 years ago by six theoreticians including British physicists Peter Higgs from Edinburgh University and Tom Kibble from Imperial College London. The discovery is the culmination of a truly remarkable scientific journey and undoubtedly the most significant scientific discovery of the twenty-first century so far. Its experimental confirmation turned out to be a monumental task requiring the creation of an accelerator and experiments of unprecedented capability and complexity, designed to discern the signatures that correspond to the Higgs boson. Thousands of scientists and engineers, in each of the ATLAS and CMS teams, came together from all four corners of the world to make this massive discovery possible.

  2. Advanced strategies for quality control of Chinese medicines.

    PubMed

    Zhao, Jing; Ma, Shuang-Cheng; Li, Shao-Ping

    2018-01-05

    Quality control is always the critical issue for Chinese medicines (CMs) with their worldwide increasing use. Different from western medicine, CMs are usually considered that multiple constituents are responsible for the therapeutic effects. Therefore, quality control of CMs is a challenge. In 2011, the strategies for quantification, related to the markers, reference compounds and approaches, in quality control of CMs were reviewed (Li, et al., J. Pharm. Biomed. Anal., 2011, 55, 802-809). Since then, some new strategies have been proposed in these fields. Therefore, the review on the strategies for quality control of CMs should be updated to improve the safety and efficacy of CMs. Herein, novel strategies related to quality marker discovery, reference compound development and advanced approaches (focused on glyco-analysis) for quality control, during 2011-2016, were summarized and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Partial characterization of chayotextle starch-based films added with ascorbic acid encapsulated in resistant starch.

    PubMed

    Martínez-Ortiz, Miguel A; Vargas-Torres, Apolonio; Román-Gutiérrez, Alma D; Chavarría-Hernández, Norberto; Zamudio-Flores, Paul B; Meza-Nieto, Martín; Palma-Rodríguez, Heidi M

    2017-05-01

    Chayotextle starch was modified by subjecting it to a dual treatment with acid and heating-cooling cycles. This caused a decrease in the content of amylose, which showed values of 30.22%, 4.80%, 3.27% and 3.57% for native chayotextle starch (NCS), starch modified by acid hydrolysis (CMS), and CMS with one (CMS1AC) and three autoclave cycles (CMS3AC), respectively. The percentage of crystallinity showed an increase of 36.9%-62% for NCS and CMS3AC. The highest content of resistant starch (RS) was observed in CMS3AC (37.05%). The microcapsules were made with CMS3AC due to its higher RS content; the total content of ascorbic acid of the microcapsules was 82.3%. The addition of different concentrations of CMS3AC microcapsules (0%, 2.5%, 6.255% and 12.5%) to chayotextle starch-based films (CSF) increased their tensile strength and elastic modulus. The content of ascorbic acid and RS in CSF was ranged from 0% to 59.4% and from 4.84% to 37.05% in the control film and in the film mixed with CMS3AC microcapsules, respectively. Water vapor permeability (WVP) values decreased with increasing concentrations of microcapsules in the films. Microscopy observations showed that higher concentrations of microcapsules caused agglomerations due their poor distribution in the matrix of the films. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Human cardiomyocyte generation from pluripotent stem cells: A state-of-art.

    PubMed

    Talkhabi, Mahmood; Aghdami, Nasser; Baharvand, Hossein

    2016-01-15

    The human heart is considered a non-regenerative organ. Worldwide, cardiovascular diseases continue to be the leading cause of death. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate human CMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular-, and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large-scale suspension culture differentiation, and development of chemically defined culture conditions. These hCMs could be useful particularly in the context of in vitro disease modeling, pharmaceutical screening and in cellular replacement therapies once the safety issues are overcome. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and current limitations. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

    PubMed

    Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

    2010-06-15

    CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation. 2010 Elsevier Ltd. All rights reserved.

  6. Origin of the CMS gene locus in rapeseed cybrid mitochondria: active and inactive recombination produces the complex CMS gene region in the mitochondrial genomes of Brassicaceae.

    PubMed

    Oshima, Masao; Kikuchi, Rie; Imamura, Jun; Handa, Hirokazu

    2010-01-01

    CMS (cytoplasmic male sterile) rapeseed is produced by asymmetrical somatic cell fusion between the Brassica napus cv. Westar and the Raphanus sativus Kosena CMS line (Kosena radish). The CMS rapeseed contains a CMS gene, orf125, which is derived from Kosena radish. Our sequence analyses revealed that the orf125 region in CMS rapeseed originated from recombination between the orf125/orfB region and the nad1C/ccmFN1 region by way of a 63 bp repeat. A precise sequence comparison among the related sequences in CMS rapeseed, Kosena radish and normal rapeseed showed that the orf125 region in CMS rapeseed consisted of the Kosena orf125/orfB region and the rapeseed nad1C/ccmFN1 region, even though Kosena radish had both the orf125/orfB region and the nad1C/ccmFN1 region in its mitochondrial genome. We also identified three tandem repeat sequences in the regions surrounding orf125, including a 63 bp repeat, which were involved in several recombination events. Interestingly, differences in the recombination activity for each repeat sequence were observed, even though these sequences were located adjacent to each other in the mitochondrial genome. We report results indicating that recombination events within the mitochondrial genomes are regulated at the level of specific repeat sequences depending on the cellular environment.

  7. Risk factors for cardiomyopathy syndrome (CMS) in Norwegian salmon farming.

    PubMed

    Bang Jensen, Britt; Brun, Edgar; Fineid, Birgitte; Larssen, Rolf Bjerke; Kristoffersen, Anja B

    2013-12-12

    Cardiomyopathy syndrome (CMS) has been an economically important disease in Norwegian aquaculture since the 1990s. In this study, data on monthly production characteristics and case registrations were combined in a cohort study and supplemented with a questionnaire-based case-control survey on management factors in order to identify risk factors for CMS. The cohort study included cases and controls from 2005 to 2012. From this dataset differences between all cases and controls were analyzed by a mixed effect multivariate logistic regression. From this we found that the probability of CMS increased with increasing time in the sea, infection pressure, and cohort size, and that cohorts which had previously been diagnosed with heart and skeletal muscle inflammation or which were in farms with a history of CMS in previous cohorts had double the odds of developing CMS. The model was then used to calculate the predicted value for each cohort from which additional data were obtained via the questionnaire-based survey and used as offset for calculating the probability of CMS in a semi-univariate analysis of additional risk factors. Finally, the model was used to calculate the probability of developing CMS in 100 different scenarios in which the cohorts were subject to increasingly worse conditions with regards to the risk factors from the dataset. We believe that this exercise is a good way of communicating the findings to farmers, so they can make informed decisions when trying to avoid CMS in their fish cohorts.

  8. The CMS Journey to LHC Physics

    ScienceCinema

    Virdee, Tejinder

    2018-04-27

    An overview of the design, the construction and physics of CMS will be given. A history of construction, encompassing the R&D; and challenges faced over the last decade and a half, will be recalled using selected examples. CMS is currently in the final stages of installation and commissioning is gathering pace. After a short status report of where CMS stands today some of the expected (great) physics to come will be outlined.

  9. The Development of Educational Environment Suited to the Japan-Specific Educational Service Using Requirements Engineering Techniques: Case Study of Running Sakai with PostgreSQL

    ERIC Educational Resources Information Center

    Terawaki, Yuki; Takahashi, Yuichi; Kodama, Yasushi; Yana, Kazuo

    2011-01-01

    This paper describes an integration of different Relational Database Management System (RDBMS) of two Course Management Systems (CMS) called Sakai and the Common Factory for Inspiration and Value in Education (CFIVE). First, when the service of CMS is provided campus-wide, the problems of user support, CMS operation and customization of CMS are…

  10. Effect of vitamin E on reversibility of renal function following discontinuation of colistin in rats: Histological and biochemical investigations.

    PubMed

    Ghlissi, Zohra; Hakim, Ahmed; Mnif, Hela; Kallel, Rim; Zeghal, Khaled; Boudawara, Tahiya; Sahnoun, Zouheir

    2018-01-01

    This study was carried out to evaluate spontaneous renal regeneration after stopping colistin methanesulfonate (CMS), which induces tubular damage, and the curative effect of Vitamin E (vit E) in rats. Animals were given the following: sterile saline (n = 6), 300,000 IU/kg/ day of CMS (n = 24), or 450,000 IU/kg/day of CMS (n = 24) for seven days. Each CMS group was subdivided into four subgroups (n = 6) and sacrificed as follows: (i) 12 h after stopping CMS, (ii) two weeks after stopping CMS, (iii) two weeks after stopping treatment with vit E, and (iv) two weeks after stopping treatment with olive oil. Subsequently, plasma creatinine (pCr), urine N-acetyl-b-D-glucosaminidase (NAG), renal tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), and renal histology were tested. CMS-induced tubular damage increased the NAG and MDA levels and decreased the SOD and GSH activities. After two weeks of stopping CMS, there was no significant renal recovery. However, treatment with vit E improved tubular regeneration and reduced the biochemical impairments. Two weeks might not be long enough for significant spontaneous renal regeneration. Improvement of renal parameters by vit E could be explained by the reduction of oxidative stress damage.

  11. Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

    PubMed

    Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

    2013-04-01

    To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

  12. Congenital abnormalities in Japanese patients with Menkes disease.

    PubMed

    Gu, Yan-Hong; Kodama, Hiroko; Kato, Tadaaki

    2012-10-01

    Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born infants with MNK is 2.8 per million live births in Japan. The aim of this study was to observe congenital malformations (CMs) in MNK patients. Subjects comprised 35 Japanese male patients with classical MNK who received copper histidine treatment. Patient clinical data were obtained anonymously from medical records or medical record summaries by pediatrician's retrospective review through a survey. We observed 21 different CMs in 14 patients. Eight of these had a single CM, while six had multiple CMs. The most frequent CM was higher arched palate with other CMs found in five patients. There was no relationship between CMs and mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also significantly lower in MNK patients with CMs (P<0.05), compared to those without CMs, even though there was no significant difference of age onset, age at diagnosis and age at start of treatment with copper histidine between both groups of patients. Sudden death occurred in three MNK patients with CMs only: two with congenital heart disease, and one with microphallus. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. SiteDB: Marshalling people and resources available to CMS

    NASA Astrophysics Data System (ADS)

    Metson, S.; Bonacorsi, D.; Dias Ferreira, M.; Egeland, R.

    2010-04-01

    In a collaboration the size of CMS (approx. 3000 users, and almost 100 computing centres of varying size) communication and accurate information about the sites it has access to is vital in co-ordinating the multitude of computing tasks required for smooth running. SiteDB is a tool developed by CMS to track sites available to the collaboration, the allocation to CMS of resources available at those sites and the associations between CMS members and the sites (as either a manager/operator of the site or a member of a group associated to the site). It is used to track the roles a person has for an associated site or group. SiteDB eases the coordination load for the operations teams by providing a consistent interface to manage communication with the people working at a site, by identifying who is responsible for a given task or service at a site and by offering a uniform interface to information on CMS contacts and sites. SiteDB provides api's and reports for other CMS tools to use to access the information it contains, for instance enabling CRAB to use "user friendly" names when black/white listing CE's, providing role based authentication and authorisation for other web based services and populating various troubleshooting squads in external ticketing systems in use daily by CMS Computing operations.

  14. Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions

    PubMed Central

    Nicole, Sophie; Azuma, Yoshiteru; Bauché, Stéphanie; Eymard, Bruno; Lochmüller, Hanns; Slater, Clarke

    2017-01-01

    Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS. PMID:29125502

  15. Impact of Psychological Screening on Routine Outpatient Care of Hematopoietic Cell Transplantation Survivors

    PubMed Central

    Hoodin, Flora; Zhao, Lili; Carey, Jillian; Levine, John E.; Kitko, Carrie

    2017-01-01

    Hematopoietic cell transplantation (HCT) recipients are at high risk for psychological distress with reported prevalence rates as high as 40%. Although published guidelines advocate periodic routine screening, it is unclear how screening affects management of psychological symptoms at routine post-HCT outpatient clinic visits. We hypothesized that providers will be more likely to act on patients’ psychological symptoms if a screening survey is completed and reviewed prior to a clinic visit. We used a brief, diagnostically focused Patient Health Questionnaire (PHQ), to assess for depressive disorders, anxiety, substance abuse, and problems in occupational or interpersonal functioning (functional disruption). Adult HCT survivors were randomized to complete the PHQ prior to meeting with their medical provider (n = 50; experimental group) or afterwards (n = 51; control group). Providers used the experimental group PHQ results at their discretion during the visits. Both providers and patients rated their satisfaction with management of psychological concerns after the visit. The prevalence of clinically significant depression (21%), anxiety (14%), or suicidal ideation (8%) did not differ between the two groups. Patients in the experimental group were significantly more likely to have discussion of psychological symptoms than the control group (68% versus 49%, P = 0.05). Medical providers were significantly more satisfied with the management of psychological issues for the experimental group (P < 0.001). Patients with depression or anxiety were significantly more likely to prefer the PHQ be used at future visits (P = 0.02 and P = 0.001 respectively). These findings suggest an informative yet brief self-report psychological screen can be easily integrated into routine care of HCT survivors, stimulates discussion of psychological symptoms, and improves provider satisfaction with psychological symptom management. Future research will evaluate whether serial prospective administration improves patient outcomes. PMID:23892043

  16. 42 CFR 425.602 - Establishing the benchmark.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

  17. 42 CFR 425.602 - Establishing the benchmark.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

  18. 42 CFR 425.602 - Establishing the benchmark.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

  19. 45 CFR 150.345 - Appeal of proposed penalty.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and... against which CMS has assessed a penalty may appeal that penalty in accordance with § 150.401 et seq. ...

  20. Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

    NASA Astrophysics Data System (ADS)

    Guo, Zhen; Du, Yu; Liu, Xianbin; Ng, Siu-Choon; Chen, Yuan; Yang, Yanhui

    2010-04-01

    Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

  1. Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model.

    PubMed

    Ghlissi, Zohra; Hakim, Ahmed; Sila, Assaad; Mnif, Hela; Zeghal, Khaled; Rebai, Tarek; Bougatef, Ali; Sahnoun, Zouheir

    2014-05-01

    We evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats. Animals were treated with sterile saline, 300000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed. CMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage. Nephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Baicalin maintains late-stage functional cardiomyocytes in embryoid bodies derived from murine embryonic stem cells.

    PubMed

    Tang, Meilin; Yin, Mengmeng; Tang, Ming; Liang, Huamin; Yu, Chong; Hu, Xinwu; Luo, Hongyan; Baudis, Birte; Haustein, Moritz; Khalil, Markus; Sarić, Tomo; Hescheler, Jürgen; Xi, Jiaoya

    2013-01-01

    Low efficiency of cardiomyocyte (CM) differentiation from embryonic stem (ES) cells limits their therapeutic use. The objective of this study was to investigate the effect of baicalin, a natural flavonoid compound, on the in vitro cardiac differentiation of murine ES cells. The induction of ES cells into cardiac-like cells was performed by embryoid body (EB)-based differentiation method. The electrophysiological properties of the ES cell-derived CMs (ES-CMs) were measured by patch-clamp. The biomarkers of ES-CMs were determined by quantitative RT-PCR and immunofluorescence. Continuous baicalin treatment decreased the size of EBs, and increased the proportion of α-actinin-positive CMs and transcript level of cardiac specific markers in beating EBs by inducing cell death of non-CMs. Baicalin increased the percentage of working ES-CMs which had typical responses to β-adrenergic and muscarinic stimulations. Baicalin maintains the late-stage functional CMs in EBs derived from murine ES cells. This study describes a new insight into the various biological effects of baicalin on cardiac differentiation of pluripotent stem cells. Copyright © 2013 S. Karger AG, Basel.

  3. The CMS dataset bookkeeping service

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

    Afaq, Anzar,; /Fermilab; Dolgert, Andrew

    2007-10-01

    The CMS Dataset Bookkeeping Service (DBS) has been developed to catalog all CMS event data from Monte Carlo and Detector sources. It provides the ability to identify MC or trigger source, track data provenance, construct datasets for analysis, and discover interesting data. CMS requires processing and analysis activities at various service levels and the DBS system provides support for localized processing or private analysis, as well as global access for CMS users at large. Catalog entries can be moved among the various service levels with a simple set of migration tools, thus forming a loose federation of databases. DBS ismore » available to CMS users via a Python API, Command Line, and a Discovery web page interfaces. The system is built as a multi-tier web application with Java servlets running under Tomcat, with connections via JDBC to Oracle or MySQL database backends. Clients connect to the service through HTTP or HTTPS with authentication provided by GRID certificates and authorization through VOMS. DBS is an integral part of the overall CMS Data Management and Workflow Management systems.« less

  4. Open access to high-level data and analysis tools in the CMS experiment at the LHC

    DOE PAGES

    Calderon, A.; Colling, D.; Huffman, A.; ...

    2015-12-23

    The CMS experiment, in recognition of its commitment to data preservation and open access as well as to education and outreach, has made its first public release of high-level data under the CC0 waiver: up to half of the proton-proton collision data (by volume) at 7 TeV from 2010 in CMS Analysis Object Data format. CMS has prepared, in collaboration with CERN and the other LHC experiments, an open-data web portal based on Invenio. The portal provides access to CMS public data as well as to analysis tools and documentation for the public. The tools include an event display andmore » histogram application that run in the browser. In addition a virtual machine containing a CMS software environment along with XRootD access to the data is available. Within the virtual machine the public can analyse CMS data, example code is provided. As a result, we describe the accompanying tools and documentation and discuss the first experiences of data use.« less

  5. Starch-based nanocapsules fabricated through layer-by-layer assembly for oral delivery of protein to lower gastrointestinal tract.

    PubMed

    Zhang, Yiping; Chi, Chengdeng; Huang, Xiaoyi; Zou, Qin; Li, Xiaoxi; Chen, Ling

    2017-09-01

    Anionic carboxymethyl starch (CMS) and cationic quaternary ammonium starch (QAS), were used to fabricate nanocapsules through electrostatic layer by layer (LbL) alternate deposition onto colloidal BSA particles. An ideal starch-based colloidal nanocapsule was achieved by adjusting the degree of substitution (DS) and weight average molecular molar mass (M w ) of CMS. The nanocapsules fabricated by CMS with lower DS or M w possessed more compact and stable core-shell structure, which favoured the BSA delivery from the upper gastrointestinal tract (GIT) to the colon. In particular, CMS/QAS nanocapsules constructed by CMS with lower DS and M w showed better colon-specific delivery and release performance in simulated GIT fluid after 7days' storage in different kinds of beverage (33.04%-46.35% in upper GIT, 52.70%-64.97% in colon, respectively). These findings demonstrated that CMS/QAS nanocapsules constructed by CMS with lower DS and M w can be further exploited as a potential oral delivery system for protein to colon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers.

    PubMed

    Couet, W; Grégoire, N; Gobin, P; Saulnier, P J; Frasca, D; Marchand, S; Mimoz, O

    2011-06-01

    Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.

  7. Exploiting analytics techniques in CMS computing monitoring

    NASA Astrophysics Data System (ADS)

    Bonacorsi, D.; Kuznetsov, V.; Magini, N.; Repečka, A.; Vaandering, E.

    2017-10-01

    The CMS experiment has collected an enormous volume of metadata about its computing operations in its monitoring systems, describing its experience in operating all of the CMS workflows on all of the Worldwide LHC Computing Grid Tiers. Data mining efforts into all these information have rarely been done, but are of crucial importance for a better understanding of how CMS did successful operations, and to reach an adequate and adaptive modelling of the CMS operations, in order to allow detailed optimizations and eventually a prediction of system behaviours. These data are now streamed into the CERN Hadoop data cluster for further analysis. Specific sets of information (e.g. data on how many replicas of datasets CMS wrote on disks at WLCG Tiers, data on which datasets were primarily requested for analysis, etc) were collected on Hadoop and processed with MapReduce applications profiting of the parallelization on the Hadoop cluster. We present the implementation of new monitoring applications on Hadoop, and discuss the new possibilities in CMS computing monitoring introduced with the ability to quickly process big data sets from mulltiple sources, looking forward to a predictive modeling of the system.

  8. Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

    PubMed

    Pols, San Y C V; van Veelen, Marie Lise C; Aarsen, Femke K; Gonzalez Candel, Antonia; Catsman-Berrevoets, Coriene E

    2017-07-01

    OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group, significantly more reported incidents of severe bleeding in the tumor bed during surgery in the pCMS group, preoperative hydrocephalus, and a mean body temperature rise of 0.5°C in the first 4 days after surgery in the pCMS group. Multiple regression analysis revealed that tumor size, tumor infiltration into or compression of the brainstem, and higher mean body temperature in the first 4 postoperative days were independent and highly significant predictors for pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated preoperative conditions, such as a maximum tumor diameter ≥ 5 cm and infiltration into or compression of the brainstem, are associated with a higher risk for the development of pCMS. Most importantly, the authors found that a 0.5°C higher mean body temperature in the first 4 postoperative days increased the odds ratio for the development of pCMS almost 5-fold. These data suggest that an important focus for the prevention of pCMS in children who have undergone medulloblastoma surgery might be rigorous maintenance of normothermia as standard care after surgery.

  9. The Consensus Molecular Subtypes of Colorectal Cancer

    PubMed Central

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-01-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759

  10. Care management service and falls prevention: a case-control study in a Chinese population.

    PubMed

    Leung, Angela Y M; Lou, Vivian W Q; Chan, Kin Sun; Yung, Alison; Chi, Iris

    2010-04-01

    This study evaluates the effect of a care management service (CMS) on falls in older adults. This is a retrospective case-control study with 78 CMS recipients as the case group who received CMS and another 312 community-dwelling frail elders as the control group.The groups were matched by age, gender, activity of daily living, cognitive impairment, and unsteady gait. Thus they were comparable in characteristics and frailty. Among the 390 participants, 89 older adults (23.0%) had falls in the 90 days prior to the survey. After controlling for the identified risk factors for falls, the odds ratio of CMS was 0.27 (95% confidence interval = 0.110-0.663, p < .01). These findings indicate that CMS recipients have a lower chance for falls compared to their counterparts. The two features of CMS (comprehensive assessment and multidisciplinary actions to reduce fall risks) are discussed.

  11. Selective depression of titanaugite in the ilmenite flotation with carboxymethyl starch

    NASA Astrophysics Data System (ADS)

    Meng, Qingyou; Yuan, Zhitao; Yu, Li; Xu, Yuankai; Du, Yusheng; Zhang, Chen

    2018-05-01

    In order to intensify the flotation separation of ilmenite from titanaugite, surface modification of mineral particles was carried out using carboxymethyl starch (CMS) by microflotation experiments, zeta potential measurements, Fourier transform infrared (FTIR) and atomic force microscopy (AFM) analysis. Microflotation results showed that CMS was a selective depressant, and it effectively enhanced the floatability difference between ilmenite and titanaugite in the pH range from 6.0 to 10.0. As it was revealed by the zeta potential, FTIR and AFM analysis, the CMS adsorption occurred onto mineral surfaces through chemisorption and hydrogen bonding, while CMS exhibited a stronger interaction with titanaugite than ilmenite. After that, the CMS adsorption impeded the adsorption of sodium oleate collector on titanaugite surfaces, giving rise to a concomitant decrease in the floatability of titanaugite. These findings exhibit great potential for CMS application in the selective flotation of ilmenite.

  12. Moving beyond the comprehensive in vitro proarrhythmia assay: Use of human-induced pluripotent stem cell-derived cardiomyocytes to assess contractile effects associated with drug-induced structural cardiotoxicity.

    PubMed

    Yang, Xi; Papoian, Thomas

    2018-02-27

    Drug-induced cardiotoxicity is a potentially severe side effect that can adversely affect myocardial contractility through structural or electrophysiological changes in cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising human cardiac in vitro model system to assess both proarrhythmic and non-proarrhythmic cardiotoxicity of new drug candidates. The scalable differentiation of hiPSCs into cardiomyocytes provides a renewable cell source that overcomes species differences present in current animal models of drug toxicity testing. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative represents a paradigm shift for proarrhythmic risk assessment, and hiPSC-CMs are an integral component of that paradigm. The recent advancements in hiPSC-CMs will not only impact safety decisions for possible drug-induced proarrhythmia, but should also facilitate risk assessment for non-proarrhythmic cardiotoxicity, where current non-clinical approaches are limited in detecting this risk before initiation of clinical trials. Importantly, emerging evidence strongly suggests that the use of hiPSC-CMs with cardiac physiological relevant measurements in vitro improves the detection of structural cardiotoxicity. Here we review high-throughput drug screening using the hiPSC-CM model as an experimentally feasible approach to assess potential contractile and structural cardiotoxicity in early phase drug development. We also suggest that the assessment of structural cardiotoxicity can be added to electrophysiological tests in the same platform to complement the Comprehensive in vitro Proarrhythmia Assay for regulatory use. Ideally, application of these novel tools in early drug development will allow for more reliable risk assessment and lead to more informed regulatory decisions in making safe and effective drugs available to the public. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  13. Comparative transcript profiling of alloplasmic male-sterile lines revealed altered gene expression related to pollen development in rice (Oryza sativa L.).

    PubMed

    Hu, Jihong; Chen, Guanglong; Zhang, Hongyuan; Qian, Qian; Ding, Yi

    2016-08-05

    Cytoplasmic male sterility (CMS) is an ideal model for investigating the mitochondrial-nuclear interaction and down-regulated genes in CMS lines which might be the candidate genes for pollen development in rice. In this study, a set of rice alloplasmic sporophytic CMS lines was obtained by successive backcrossing of Meixiang B, with three different cytoplasmic types: D62A (D type), ZS97A (WA type) and XQZ-A (DA type). Using microarray, the anther transcript profiles of the three indica rice CMS lines revealed 622 differentially expressed genes (DEGs) in each of the three CMS lines compared with the maintainer line Meixiang B. GO and MapMan analysis indicated that these DEGs were mainly involved in lipid metabolism and cell wall organization. Compared with the gene expression of sporophytic and gametophytic CMS lines, 303 DEGs were identified and 56 of them were down-regulated in all the CMS lines of rice. These down-regulated DEGs in the CMS lines were found to be involved in tapetum or cell wall formation and their suppressed expression might be related to male sterility. Weighted gene co-expression network analysis (WGCNA) revealed that two modules were significantly associated with male sterility and many hub genes that were differentially expressed in the CMS lines. A large set of putative genes involved in anther development was identified in the present study. The results will give some information for the nuclear gene regulation by different cytoplasmic genotypes and provide a rich resource for further functional research on the pollen development in rice.

  14. Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue.

    PubMed

    Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E A; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad; Khalil, Markus

    2014-03-15

    Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium.

  15. Mesenchymal Stem Cells and Their Conditioned Medium Improve Integration of Purified Induced Pluripotent Stem Cell–Derived Cardiomyocyte Clusters into Myocardial Tissue

    PubMed Central

    Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E.A.; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad

    2014-01-01

    Induced pluripotent stem cell–derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium. PMID:24219308

  16. A Novel Cytoplasmic Male Sterility in Brassica napus (inap CMS) with Carpelloid Stamens via Protoplast Fusion with Chinese Woad.

    PubMed

    Kang, Lei; Li, Pengfei; Wang, Aifan; Ge, Xianhong; Li, Zaiyun

    2017-01-01

    A novel cytoplasmic male sterility (CMS) in Brassica napus (inap CMS) was selected from the somatic hybrid with Isatis indigotica (Chinese woad) by recurrent backcrossing. The male sterility was caused by the conversion of tetradynamous stamens into carpelloid structures with stigmatoid tissues at their tips and ovule-like tissues in the margins, and the two shorter stamens into filaments without anthers. The feminized development of the stamens resulted in the complete lack of pollen grains, which was stable in different years and environments. The pistils of inap CMS displayed normal morphology and good seed-set after pollinated by B. napus . Histological sections showed that the developmental alteration of the stamens initiated at the stage of stamen primordium differentiation. AFLP analysis of the nuclear genomic composition with 23 pairs of selective primers detected no woad DNA bands in inap CMS. Twenty out of 25 mitochondrial genes originated from I. indigotica , except for cox2-2 which was the recombinant between cox2 from woad and cox2-2 from rapeseed. The novel cox2-2 was transcribed in flower buds of inap CMS weakly and comparatively with the fertile B. napus addition line Me harboring one particular woad chromosome. The restorers of other autoplasmic and alloplasmic CMS systems in rapeseed failed to restore the fertility of inap CMS and the screening of B. napus wide resources found no fertility restoration variety, showing its distinct origin and the related mechanism of sterility. The reasons for the mitochondrial rearrangements and the breeding of the restorer for the novel CMS system were discussed.

  17. Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability.

    PubMed

    Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Azimi, Mandana; Valizadeh, Hadi

    2009-09-01

    The solubility and dissolution rate of active ingredients are of major importance in preformulation studies of pharmaceutical dosage forms. In the present study, passively absorbed drugs are classified based on their intrinsic dissolution rate (IDR) and their intestinal permeabilities. IDR was determined by measuring the dissolution of a non-disintegrating disk of drug, and effective intestinal permeability of tested drugs in rat jejunum was determined using single perfusion technique. The obtained intrinsic dissolution rate values were in the range of 0.035-56.8 mg/min/cm(2) for tested drugs. The minimum and maximum intestinal permeabilities in rat intestine were determined to be 1.6 x 10(-5) and 2 x 10(-4)cm/s, respectively. Four classes of drugs were defined: Category I: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR>1(mg/min/cm(2)), Category II: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)), Category III: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR>1 (mg/min/cm(2)) and Category IV: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)). According to the results obtained and proposed classification of drugs, it is concluded that drugs could be categorized correctly based on their IDR and intestinal permeability values.

  18. Comparison of American Academy of Sleep Medicine (AASM) versus Center for Medicare and Medicaid Services (CMS) polysomnography (PSG) scoring rules on AHI and eligibility for continuous positive airway pressure (CPAP) treatment.

    PubMed

    Korotinsky, Arkady; Assefa, Samson Z; Diaz-Abad, Montserrat; Wickwire, Emerson M; Scharf, Steven M

    2016-12-01

    Obstructive sleep apnea (OSA) is an important clinical condition. Eligibility for treatment usually depends on disease severity, measured as the apnea-hypopnea index (AHI), equal to the sum of apneas plus hypopneas per hour of sleep. There is divergence on scoring rules for hypopneas between the recommendations of the American Academy of Sleep Medicine (AASM) and the Center for Medicare Services (CMS), the latter being more restrictive. Thus, patients could be eligible for treatment under AASM rules, but not under CMS rules. Sleep laboratory records of 112 consecutive patients were reviewed (85 < 65, 27 ≥ 65 years old). AHI was calculated both by AASM and by CMS criteria. Information on demographics, and important comorbidities, was also reviewed. AHI was lower in younger patients using CMS criteria. However, differences in AHI using the two sets of criteria were not significantly different in the older patients. Incorporating all criteria for eligibility (severity, presence of certain comorbid conditions) for treatment, we found that fewer younger patients would be eligible using CMS criteria, but among the older patients, eligibility for treatment was the same whether AASM or CMS criteria were used. Use of CMS criteria for scoring hypopneas results in lower estimates of OSA severity, with fewer younger patients eligible for treatment. However, among Medicare age patients, the rate of treatment eligibility was the same whether AASM or CMS scoring rules were used.

  19. The use of herbs by california midwives.

    PubMed

    Dennehy, Cathi; Tsourounis, Candy; Bui, Lindsey; King, Tekoa L

    2010-01-01

    To characterize herbal product use (prevalence, types, indications) among Certified Nurse Midwives/Certified Midwives (CNMs/CMs) and Licensed Midwives (LMs) practicing in the state of California and to describe formal education related to herbal products received by midwives during midwifery education. Cross-sectional survey/California/Practicing midwives. A list of LMs and CNMs/CMs practicing in California was obtained through the California Medical Board (CMB) and the American College of Nurse Midwives (ACNM), respectively. The survey was mailed to 343 CNMs/CMs (one third of the ACNM mailing list) and 157 LMs (the complete CMB mailing list). Of the 500 surveys mailed, 40 were undeliverable, 146 were returned, and 7 were excluded (30% response rate). Of the 139 completed surveys, 58/102 (57%) of CNMs/CMs and 35/37 (95%) of LMs used herbs, and LMs were more comfortable than CNMs/CMs in recommending herbs to their patients. A majority of LMs had >20 hours of midwifery education on herbs whereas a majority of CNMs/CMs received 0 to 5 hours. Some CNMs/CMs indicated that their practice site limited their ability to use herbs. Common conditions in which LMs and CNMs/CMs used herbs were nausea/vomiting (86% vs. 83%), labor induction (89% vs. 58%), and lactation (86% vs. 65%). Specific herbs for all indications are described. Licensed midwives were more likely than CNMs/CMs to use herbs in clinical practice. This trend was likely a reflection of the amount of education devoted to herbs as well as herbal use limitations that may be encountered in institutional facilities. © 2010 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  20. 45 CFR 150.323 - Determining the amount of penalty-other matters as justice may require.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... Determining the amount of penalty—other matters as justice may require. CMS may take into account other...

  1. Extensive structural variations between mitochondrial genomes of CMS and normal peppers (Capsicum annuum L.) revealed by complete nucleotide sequencing.

    PubMed

    Jo, Yeong Deuk; Choi, Yoomi; Kim, Dong-Hwan; Kim, Byung-Dong; Kang, Byoung-Cheorl

    2014-07-04

    Cytoplasmic male sterility (CMS) is an inability to produce functional pollen that is caused by mutation of the mitochondrial genome. Comparative analyses of mitochondrial genomes of lines with and without CMS in several species have revealed structural differences between genomes, including extensive rearrangements caused by recombination. However, the mitochondrial genome structure and the DNA rearrangements that may be related to CMS have not been characterized in Capsicum spp. We obtained the complete mitochondrial genome sequences of the pepper CMS line FS4401 (507,452 bp) and the fertile line Jeju (511,530 bp). Comparative analysis between mitochondrial genomes of peppers and tobacco that are included in Solanaceae revealed extensive DNA rearrangements and poor conservation in non-coding DNA. In comparison between pepper lines, FS4401 and Jeju mitochondrial DNAs contained the same complement of protein coding genes except for one additional copy of an atp6 gene (ψatp6-2) in FS4401. In terms of genome structure, we found eighteen syntenic blocks in the two mitochondrial genomes, which have been rearranged in each genome. By contrast, sequences between syntenic blocks, which were specific to each line, accounted for 30,380 and 17,847 bp in FS4401 and Jeju, respectively. The previously-reported CMS candidate genes, orf507 and ψatp6-2, were located on the edges of the largest sequence segments that were specific to FS4401. In this region, large number of small sequence segments which were absent or found on different locations in Jeju mitochondrial genome were combined together. The incorporation of repeats and overlapping of connected sequence segments by a few nucleotides implied that extensive rearrangements by homologous recombination might be involved in evolution of this region. Further analysis using mtDNA pairs from other plant species revealed common features of DNA regions around CMS-associated genes. Although large portion of sequence context was shared by mitochondrial genomes of CMS and male-fertile pepper lines, extensive genome rearrangements were detected. CMS candidate genes located on the edges of highly-rearranged CMS-specific DNA regions and near to repeat sequences. These characteristics were detected among CMS-associated genes in other species, implying a common mechanism might be involved in the evolution of CMS-associated genes.

  2. Final Technical Report for ARRA Funding

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

    Rusack, Roger; Mans, Jeremiah; Poling, Ronald

    Final technical report of the University of Minnesota experimental high energy physics group for ARRA support. The Cryogenic Dark Matter Experiment (CDMS) used the funds received to construct a new passive shield to protect a high-purity germanium detector located in the Soudan mine in Northern Minnesota from cosmic rays. The BESIII and the CMS groups purchased computing hardware to assemble computer farms for data analysis and to generate large volumes of simulated data for comparison with the data collected.

  3. Content management systems and E-commerce: a comparative case study

    NASA Astrophysics Data System (ADS)

    Al Rasheed, Amal A.; El-Masri, Samir D.

    2011-12-01

    The need for CMS's to create and edit e-commerce websites has increased with the growing importance of e-commerce. In this paper, the various features essential for e-commerce CMS's are explored. The aim of the paper was to find the best CMS solution for e-commerce which includes the best of both CMS and store management. Accordingly, we conducted a study on three popular open source CMS's for e-commerce: VirtueMart from Joomla!, Ubercart from Drupal, and Magento. We took into account features like hosting and installation, performance, support/community, content management, add on modules and functional features. We concluded with improvements that could be made in order to alleviate problems.

  4. Using the CMS threaded framework in a production environment

    DOE PAGES

    Jones, C. D.; Contreras, L.; Gartung, P.; ...

    2015-12-23

    During 2014, the CMS Offline and Computing Organization completed the necessary changes to use the CMS threaded framework in the full production environment. We will briefly discuss the design of the CMS Threaded Framework, in particular how the design affects scaling performance. We will then cover the effort involved in getting both the CMSSW application software and the workflow management system ready for using multiple threads for production. Finally, we will present metrics on the performance of the application and workflow system as well as the difficulties which were uncovered. As a result, we will end with CMS' plans formore » using the threaded framework to do production for LHC Run 2.« less

  5. Development of an expert system prototype for determining software functional requirements for command management activities at NASA Goddard

    NASA Technical Reports Server (NTRS)

    Liebowitz, J.

    1985-01-01

    The development of an expert system prototype for determining software functional requirements for NASA Goddard's Command Management System (CMS) is described. The role of the CMS is to transform general requests into specific spacecraft commands with command execution conditions. The CMS is part of the NASA Data System which entails the downlink of science and engineering data from NASA near-earth satellites to the user, and the uplink of command and control data to the spacecraft. Subjects covered include: the problem environment of determining CMS software functional requirements; the expert system approach for handling CMS requirements development; validation and evaluation procedures for the expert system.

  6. Triggering on New Physics with the CMS Detector

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

    Bose, Tulika

    The BU CMS group led by PI Tulika Bose has made several significant contributions to the CMS trigger and to the analysis of the data collected by the CMS experiment. Group members have played a leading role in the optimization of trigger algorithms, the development of trigger menus, and the online operation of the CMS High-Level Trigger. The group’s data analysis projects have concentrated on a broad spectrum of topics that take full advantage of their strengths in jets and calorimetry, trigger, lepton identification as well as their considerable experience in hadron collider physics. Their publications cover several searches formore » new heavy gauge bosons, vector-like quarks as well as diboson resonances.« less

  7. Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

    DOE PAGES

    Adams, T.; Adzic, P.; Ahuja, S.; ...

    2016-04-11

    The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

  8. Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.

    PubMed

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2016-10-10

    To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

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

    Adams, T.; Adzic, P.; Ahuja, S.

    The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

  10. Concurrent Flame Growth, Spread and Extinction over Composite Fabric Samples in Low Speed Purely Forced Flow in Microgravity

    NASA Technical Reports Server (NTRS)

    Zhao, Xiaoyang; T'ien, James S.; Ferkul, Paul V.; Olson, Sandra L.

    2015-01-01

    As a part of the NASA BASS and BASS-II experimental projects aboard the International Space Station, flame growth, spread and extinction over a composite cotton-fiberglass fabric blend (referred to as the SIBAL fabric) were studied in low-speed concurrent forced flows. The tests were conducted in a small flow duct within the Microgravity Science Glovebox. The fuel samples measured 1.2 and 2.2 cm wide and 10 cm long. Ambient oxygen was varied from 21% down to 16% and flow speed from 40 cm/s down to 1 cm/s. A small flame resulted at low flow, enabling us to observe the entire history of flame development including ignition, flame growth, steady spread (in some cases) and decay at the end of the sample. In addition, by decreasing flow velocity during some of the tests, low-speed flame quenching extinction limits were found as a function of oxygen percentage. The quenching speeds were found to be between 1 and 5 cm/s with higher speed in lower oxygen atmosphere. The shape of the quenching boundary supports the prediction by earlier theoretical models. These long duration microgravity experiments provide a rare opportunity for solid fuel combustion since microgravity time in ground-based facilities is generally not sufficient. This is the first time that a low-speed quenching boundary in concurrent spread is determined in a clean and unambiguous manner.

  11. Epidemiological study of chronic mountain sickness in natives of Spiti Valley in the Greater Himalayas.

    PubMed

    Negi, Prakash Chand; Asotra, Sanjeev; V, Ravi Kumar; Marwah, Rajeev; Kandoria, Arvind; Ganju, Neeraj Kumar; Sharma, Rajesh; Bhardwaj, Rajeev

    2013-09-01

    This study determined the prevalence of chronic mountain sickness (CMS) and its predisposing factors among natives of Spiti Valley in the northern state of Indian Himalayas. A cross-sectional survey study was conducted in natives of Spiti Valley aged ≥ 20 years residing at altitudes of 3000 to 4200 meters. CMS was diagnosed using Qinghai criteria. Demographics, behavioral characteristics, specified symptoms of CMS were recorded, including BP, anthropometrics, evidence of RHF, PAH, and severe cyanosis. ECG, echocardiography, PFT, and Sao2 were recorded, and Hb level was estimated with the cyanmethhemoglobin method. 694 subjects free of cardiorespiratory diseases were analyzed. Prevalence of CMS was 28.7%, (95% C.I. of 25.9%-32.8%) and was higher in women than in men (36.6% vs. 15.7%, p<0.001). Erythrocythemia and hypoxemia were recorded in 10.5% and 7.5%, respectively. Age, truncal obesity, female gender, altitude of residence, and physical activity index were independent predictors of CMS with z statistics of 4.2, 2.29, -3.7, 2.8, and -2.8, respectively, and were statistically significant p<0.001. 6.2% of the surveyed population had HAPH. 28.7% (95% C.I. of 25.9%-32.8%) of the natives of the Spiti Valley in the Indian Himalayas are affected with CMS. Higher prevalence of CMS amongst women needs further studies. Westernized lifestyle appears to have predisposition to CMS.

  12. Quantitative proteomic analysis of CMS-related changes in Honglian CMS rice anther.

    PubMed

    Sun, Qingping; Hu, Chaofeng; Hu, Jun; Li, Shaoqing; Zhu, Yingguo

    2009-10-01

    Honglian (HL) cytoplasmic male sterility (CMS) is one of the rice CMS types and has been widely used in hybrid rice production in China. The CMS line (Yuetai A, YTA) has a Yuetai B (maintainer line, YTB) nuclear genome, but has a rearranged mitochondrial (mt) genome consisting of Yuetai B. The fertility of hybrid (HL-6) was restored by restorer gene in nuclear genome of restorer line (9311). We used isotope-code affinity tag (ICAT) technology to perform the protein profiling of uninucleate stage rice anther and identify the CMS-HL related proteins. Two separate ICAT analyses were performed in this study: (1) anthers from YTA versus anthers from YTB, and (2) anthers from YTA versus anthers from HL-6. Based on the two analyses, a total of 97 unique proteins were identified and quantified in uninucleate stage rice anther under the error rate of less than 10%, of which eight proteins showed abundance changes of at least twofold between YTA and YTB. Triosephosphate isomerase, fructokinase II, DNA-binding protein GBP16 and ribosomal protein L3B were over-expressed in YTB, while oligopeptide transporter, floral organ regulator 1, kinase and S-adenosyl-L: -methionine synthetase were over-expressed in YTA. Reduction of the proteins associated with energy production and lesser ATP equivalents detected in CMS anther indicated that the low level of energy production played an important role in inducing CMS-HL.

  13. Delayed expression of SAGs correlates with longevity in CMS wheat plants compared to its fertile plants.

    PubMed

    Semwal, Vimal Kumar; Singh, Bhupinder; Khanna-Chopra, Renu

    2014-04-01

    Reproductive sinks regulate monocarpic senescence in crop plants. Monocarpic senescence was studied in wheat fertile (cv. HW 2041) and its isonuclear cytoplasmic male sterile (CMS) line. CMS plants exhibited slower rate of senescence accompanied by longer green leaf area duration and slower deceleration in chlorophyll, protein content, PN and rubisco content coupled with lower protease activities than fertile (F) plants. CMS plants also exhibited lower ROS levels and less membrane damage than F plants. CMS plants maintained better antioxidant defense, less oxidative damage in chloroplast and higher transcript levels of both rbcL and rbcS genes during senescence than F plants. F plants exhibited early induction and higher expression of SAGs like serine and cysteine proteases, glutamine synthetases GS1 and GS2, WRKY53 transcription factor and decline in transcript levels of CAT1 and CAT2 genes than CMS plants. Hence, using genetically fertile and its CMS line of wheat it is confirmed that delayed senescence in the absence of reproductive sinks is linked with slower protein oxidation, rubisco degradation and delayed activation of SAGs. Better antioxidant defense in chloroplasts at later stages of senescence was able to mitigate the deleterious effects of ROS in CMS plants. We propose that delayed increase in ROS in cytoplasmic male sterile wheat plants resulted in delayed activation of WRKY53, SAGs and the associated biochemical changes than fertile plants.

  14. Does Nursing Facility Use of Habilitation Therapy Improve Performance on Quality Measures?

    PubMed

    Fitzler, Sandra; Raia, Paul; Buckley, Fredrick O; Wang, Mei

    2016-12-01

    The purpose of the project, Centers for Medicare & Medicaid Services (CMS) Innovation study, was to evaluate the impact on 12 quality measures including 10 Minimum Data Set (MDS) publicly reported measures and 2 nursing home process measures using habilitation therapy techniques and a behavior team to manage dementia-related behaviors. A prospective design was used to assess the changes in the measures. A total of 30 Massachusetts nursing homes participated in the project over a 12-month period. Project participation required the creation of an interdisciplinary behavior team, habilitation therapy training, facility visit by the program coordinator, attendance at bimonthly support and sharing calls, and monthly collection of process measure data. Participating facilities showed improvement in 9 of the 12 reported measures. Findings indicate potential quality improvement in having nursing homes learn habilitation therapy techniques and know how to use the interdisciplinary team to manage problem behaviors. © The Author(s) 2016.

  15. Prediction of three social cognitive-motivational structure types.

    PubMed

    Malerstein, A J; Ahern, M M; Pulos, S

    2001-10-01

    Previously, using interviews from Baumrind's longitudinal study, three cognitive-motivational structures (CMSs) were predicted in 68 adolescents from caregiving settings and from the CMS types of their mothers, based on the mothers' interviews elicited six years earlier. CMS theory proposes that during Piaget's Concrete Operational Period care-receiving influences the child's adoption of a social cognitive style, which corresponds to one of Piaget's stages of cognitive development. One who is classified as an Operational experiences the caregiving setting as tuned to the child's long-term interests, becomes focused on function and control of function and grasps the distinctions between and gradations of social attributes. One classified as future Intuitive experiences the caregiving as insufficient or unreliable and becomes focused on getting and having, and assesses social situations based on current striking dimensions. A person classified as being future Symbolic experiences the caregiving as out of tune with the self or the world, becomes focused on identity and emotional closeness, and may define self or object by a single attribute. This previous study did not distinguish between the influence of caregiving (including mothers' CMS) on the formation of adolescent CMS type and the possible constancy of CMS type from ages 9 to 15 years. The current study was designed to distinguish between these two possibilities, using data from 67 of the same mothers. Mothers' interviews were purged of descriptions of her child's behavior. Another interview was composed of the purged descriptions of child behavior. This was also done for interviews held when the child was 4 and 15 as well as at 9. From interviews with descriptions of child behavior purged, mother's CMS type at the child's age of 4 and 9 yr. agreed with her adolescent's previously assigned CMS type (p<.05), and caregiving setting at 9 years predicted the adolescent's CMS type (p<.05). From interviews composed of descriptions of only the child's behavior, adolescent CMS type agreed with previously assigned adolescent CMS type (p<.01). Findings were consonant with the idea that CMS type formation is influenced at about Age 9 and sufficiently established to be recognized at Age 15.

  16. Global transcriptomic analysis of induced cardiomyocytes predicts novel regulators for direct cardiac reprogramming.

    PubMed

    Talkhabi, Mahmood; Razavi, Seyed Morteza; Salari, Ali

    2017-06-01

    Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs. To this end, many different combinations of TFs (±microRNAs) have been reported for direct reprogramming of mouse or human fibroblasts to iCMs, although their efficiencies remain very low. It seems that the investigated TFs and microRNAs are not sufficient for efficient direct cardiac reprogramming and other cardiac specific factors may be required for increasing iCM production efficiency, as well as the quality of iCMs. Here, we analyzed gene expression data of cardiac fibroblast (CFs), iCMs and adult cardiomyocytes (aCMs). The up-regulated and down-regulated genes in CMs (aCMs and iCMs) were determined as CM and CF specific genes, respectively. Among CM specific genes, we found 153 transcriptional activators including some cardiac and non-cardiac TFs that potentially activate the expression of CM specific genes. We also identified that 85 protein kinases such as protein kinase D1 (PKD1), protein kinase A (PRKA), calcium/calmodulin-dependent protein kinase (CAMK), protein kinase C (PRKC), and insulin like growth factor 1 receptor (IGF1R) that are strongly involved in establishing CM identity. CM gene regulatory network constructed using protein kinases, transcriptional activators and intermediate proteins predicted some new transcriptional activators such as myocyte enhancer factor 2A (MEF2A) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), which may be required for qualitatively and quantitatively efficient direct cardiac reprogramming. Taken together, this study provides new insights into the complexity of cell fate conversion and better understanding of the roles of transcriptional activators, signaling pathways and protein kinases in increasing the efficiency of direct cardiac reprogramming and maturity of iCMs.

  17. Comparison of the performance of the CMS Hierarchical Condition Category (CMS-HCC) risk adjuster with the Charlson and Elixhauser comorbidity measures in predicting mortality.

    PubMed

    Li, Pengxiang; Kim, Michelle M; Doshi, Jalpa A

    2010-08-20

    The Centers for Medicare and Medicaid Services (CMS) has implemented the CMS-Hierarchical Condition Category (CMS-HCC) model to risk adjust Medicare capitation payments. This study intends to assess the performance of the CMS-HCC risk adjustment method and to compare it to the Charlson and Elixhauser comorbidity measures in predicting in-hospital and six-month mortality in Medicare beneficiaries. The study used the 2005-2006 Chronic Condition Data Warehouse (CCW) 5% Medicare files. The primary study sample included all community-dwelling fee-for-service Medicare beneficiaries with a hospital admission between January 1st, 2006 and June 30th, 2006. Additionally, four disease-specific samples consisting of subgroups of patients with principal diagnoses of congestive heart failure (CHF), stroke, diabetes mellitus (DM), and acute myocardial infarction (AMI) were also selected. Four analytic files were generated for each sample by extracting inpatient and/or outpatient claims for each patient. Logistic regressions were used to compare the methods. Model performance was assessed using the c-statistic, the Akaike's information criterion (AIC), the Bayesian information criterion (BIC) and their 95% confidence intervals estimated using bootstrapping. The CMS-HCC had statistically significant higher c-statistic and lower AIC and BIC values than the Charlson and Elixhauser methods in predicting in-hospital and six-month mortality across all samples in analytic files that included claims from the index hospitalization. Exclusion of claims for the index hospitalization generally led to drops in model performance across all methods with the highest drops for the CMS-HCC method. However, the CMS-HCC still performed as well or better than the other two methods. The CMS-HCC method demonstrated better performance relative to the Charlson and Elixhauser methods in predicting in-hospital and six-month mortality. The CMS-HCC model is preferred over the Charlson and Elixhauser methods if information about the patient's diagnoses prior to the index hospitalization is available and used to code the risk adjusters. However, caution should be exercised in studies evaluating inpatient processes of care and where data on pre-index admission diagnoses are unavailable.

  18. Getting Started with Drupal WebCMS

    EPA Pesticide Factsheets

    Drupal WebCMS is accessible to EPA employees, and to onsite and offsite contractors. There are several roles in Drupal WebCMS and each allows a certain set of actions in the system. Users can have different roles in different web areas.

  19. Sickle cell disease: reference values and interhemispheric differences of nonimaging transcranial Doppler blood flow parameters.

    PubMed

    Arkuszewski, M; Krejza, J; Chen, R; Kwiatkowski, J L; Ichord, R; Zimmerman, R; Ohene-Frempong, K; Desiderio, L; Melhem, E R

    2011-09-01

    TCD screening is widely used to identify children with SCD at high risk of stroke. Those with high mean flow velocities in major brain arteries have increased risk of stroke. Thus, our aim was to establish reference values of interhemispheric differences and ratios of blood flow Doppler parameters in the tICA, MCA, and ACA as determined by conventional TCD in children with sickle cell anemia. Reference limits of blood flow parameters were established on the basis of a consecutive cohort of 56 children (mean age, 100 ± 40 months; range, 29-180 months; 30 females) free of neurologic deficits and intracranial stenosis detectable by MRA, with blood flow velocities <170 cm/s by conventional TCD. Reference limits were estimated by using tolerance intervals, within which are included with a probability of .90 of all possible data values from 95% of a population. Average peak systolic velocities were significantly higher in the right hemisphere in the MCA and ACA (185 ± 28 cm/s versus 179 ± 27 and 152 ± 30 cm/s versus 143 ± 34 cm/s respectively). Reference limits for left-to-right differences in the mean flow velocities were the following: -43 to 33 cm/s for the MCA; -49 to 38 cm/s for the ACA, and -38 to 34 cm/s for the tICA, respectively. Respective reference limits for left-to-right velocity ratios were the following: 0.72 to 1.25 cm/s for the MCA; 0.62 to 1.39 cm/s for the ACA, and 0.69 to 1.27 cm/s for the tICA. Flow velocities in major arteries were inversely related to age and Hct or Hgb. The study provides reference intervals of TCD flow velocities and their interhemispheric differences and ratios that may be helpful in identification of intracranial arterial stenosis in children with SCD undergoing sonographic screening for stroke prevention.

  20. Transcriptome sequencing and de novo analysis of cytoplasmic male sterility and maintenance in JA-CMS cotton.

    PubMed

    Yang, Peng; Han, Jinfeng; Huang, Jinling

    2014-01-01

    Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS.

  1. Transcriptome Sequencing and De Novo Analysis of Cytoplasmic Male Sterility and Maintenance in JA-CMS Cotton

    PubMed Central

    Yang, Peng; Han, Jinfeng; Huang, Jinling

    2014-01-01

    Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS. PMID:25372034

  2. Buzz in Paris: flower production and plant-pollinator interactions in plants from contrasted urban and rural origins.

    PubMed

    Desaegher, James; Nadot, Sophie; Dajoz, Isabelle; Colas, Bruno

    2017-12-01

    Urbanisation, associated with habitat fragmentation, affects pollinator communities and insect foraging behaviour. These biotic changes are likely to select for modified traits in insect-pollinated plants from urban populations compared to rural populations. To test this hypothesis, we conducted an experiment involving four plant species commonly found in both urban and rural landscapes of the Île-de-France region (France): Cymbalaria muralis, Geranium robertianum, Geum urbanum and Prunella vulgaris. The four species were grown in four urban and four rural experimental sites in 2015. For each species and each experimental site, plants were grown from seeds collected in five urban and five rural locations. During flowering, we observed flower production and insect-flower interactions during 14 weeks and tested for the effects of experimental site location and plant origin on flower production and on the number of floral visits. The study species had various flower morphology and hence were visited by different floral visitors. The effect of experimental sites and seed origin also varied among study species. We found that (1) insect visits on P. vulgaris were more frequent in rural than in urban sites; (2) for C. muralis, the slope relating the number of pollinator visits to the number of flowers per individual was steeper in urban versus rural sites, suggesting a greater benefit in allocating resources to flower production in urban conditions; (3) as a likely consequence, C. muralis tended to produce more flowers in plants from urban versus rural origin.

  3. Genetic control of invasive plants species using selfish genetic elements

    PubMed Central

    Hodgins, Kathryn A; Rieseberg, Loren; Otto, Sarah P

    2009-01-01

    Invasive plants cause substantial environmental damage and economic loss. Here, we explore the possibility that a selfish genetic element found in plants called cytoplasmic male sterility (CMS) could be exploited for weed control. CMS is caused by mutations in the mitochondrial genome that sterilize male reproductive organs. We developed an analytical model and a spatial simulation to assess the use of CMS alleles to manage weed populations. Specifically, we examined how fertility, selfing, pollen limitation and dispersal influenced extinction rate and time until extinction in populations where CMS arises. We found that the introduction of a CMS allele can cause rapid population extinction, but only under a restricted set of conditions. Both models suggest that the CMS strategy will be appropriate for species where pollen limitation is negligible, inbreeding depression is high and the fertility advantage of females over hermaphrodites is substantial. In general, spatial structure did not have a strong influence on the simulation outcome, although low pollen dispersal and intermediate levels of seed dispersal tended to reduce population extinction rates. Given these results, the introduction of CMS alleles into a population of invasive plants probably represents an effective control method for only a select number of species. PMID:25567898

  4. A study on size effect of carboxymethyl starch nanogel crosslinked by electron beam radiation

    NASA Astrophysics Data System (ADS)

    Binh, Doan; Pham Thi Thu Hong; Nguyen Ngoc Duy; Nguyen Thanh Duoc; Nguyen Nguyet Dieu

    2012-07-01

    The formation of carboxymethyl starch (CMS) nanogel with 50 nm less particle size was carried out through a radiation crosslinked process on the electron beam (EB) linear accelerator. Changes of intrinsic viscosities and weight averaged molecular weight in the CMS concentration, which ranged from 3 to 10 mg ml-1 in absorbed doses were investigated. There were some new peaks in the 1H NMR spectra of CMS nanogel compared with those of CMS polymer. These results were anticipated that the predominant intramolecular crosslinking of dilute CMS aqueous solution occurred while being exposed to a short intense pulse of ionizing radiation. Hydrodynamic radius (often called particle size, Rh) and distribution of particle size were measured by a dynamic light scattering technique. The radiation yield of intermolecular crosslinking of CMS solution was calculated from the expression of Gx (Charlesby, 1960; Jung-Chul, 2010). The influence of the "size effect" was demonstrated by testing culture of Lactobacillus bacteria on MRS agar culture medium containing CMS nanogel and polymer. Results showed that the number of Lactobacillus bacteria growing on nanogel containing culture medium is about 170 cfu/ml and on polymer containing culture medium is only 6 cfu/ml.

  5. Exploiting Analytics Techniques in CMS Computing Monitoring

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

    Bonacorsi, D.; Kuznetsov, V.; Magini, N.

    The CMS experiment has collected an enormous volume of metadata about its computing operations in its monitoring systems, describing its experience in operating all of the CMS workflows on all of the Worldwide LHC Computing Grid Tiers. Data mining efforts into all these information have rarely been done, but are of crucial importance for a better understanding of how CMS did successful operations, and to reach an adequate and adaptive modelling of the CMS operations, in order to allow detailed optimizations and eventually a prediction of system behaviours. These data are now streamed into the CERN Hadoop data cluster formore » further analysis. Specific sets of information (e.g. data on how many replicas of datasets CMS wrote on disks at WLCG Tiers, data on which datasets were primarily requested for analysis, etc) were collected on Hadoop and processed with MapReduce applications profiting of the parallelization on the Hadoop cluster. We present the implementation of new monitoring applications on Hadoop, and discuss the new possibilities in CMS computing monitoring introduced with the ability to quickly process big data sets from mulltiple sources, looking forward to a predictive modeling of the system.« less

  6. Gender differences in CMS and the effects of antidepressant venlafaxine in rats.

    PubMed

    Xing, Yanli; He, Jie; Hou, Jian; Lin, Fei; Tian, Jingwei; Kurihara, Hiroshi

    2013-11-01

    Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

    PubMed

    Raschke, Robert A; Groves, Robert H; Khurana, Hargobind S; Nikhanj, Nidhi; Utter, Ethel; Hartling, Didi; Stoffer, Brenda; Nunn, Kristina; Tryon, Shona; Bruner, Michelle; Calleja, Maria; Curry, Steven C

    2017-01-01

    Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

  8. 76 FR 18766 - Early Retiree Reinsurance Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-9996-N] Early Retiree Reinsurance Program AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice. SUMMARY: This notice announces that CMS is exercising its authority under section 1102(f) of the...

  9. 42 CFR 417.142 - Requirements for qualification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....142 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... assurances specified in paragraphs (b) through (f) of this section, as appropriate. (2) CMS determines... entity, within 30 days of CMS's determination, provides written assurances, satisfactory to CMS, that it...

  10. Using a 1200 kHz workhorse ADCP with mode 12 to measure near bottom mean currents

    USGS Publications Warehouse

    Martini, M.; ,

    2003-01-01

    Using high frequency Acoustic Doppler Current (ADCP) profiling technology, it is possible to make high-resolution measurements of mean current profiles within a few meters of the seabed. In coastal applications, mean current speeds may be 10 cm/s or less, and oscillatory wave currents may exceed 100 cm/s during storm events. To resolve mean flows of 10 cm/s or less under these conditions, accuracies of 1 cm/s or better are desirable.

  11. Supporting of the Fathers to Visit Their Infants in Neonatal Intensive Care Unit Decreases Their Stress Level: A Pretest-Posttest Quasi-Experimental Study.

    PubMed

    Kardaş Özdemir, Funda; Küçük Alemdar, Dilek

    2017-05-01

    It is known that fathers whose infants are hospitalized in NICUs (Neonatal Intensive Care Units) are severely stressed. This study was conducted for the purpose of determining the effect of supporting and visiting infants in NICUs on stress levels of Turkish fathers. This was a pretest-posttest quasi-experimental study. The population of the study consisted of 47 fathers who had their infants receiving treatment in NICU at a state hospital in the eastern Turkey and agreed to participate in the study. The data were collected by using "Father-Infant Introductory Information Form" and "Parental Stressor Scale: Neonatal Intensive Care Unit, PSS:NICU". When comparing the PSS:NICU total mean scores of the fathers before and after interventions; it was determined that their mean scores were higher before visits compared to those obtained after interventions and the difference between them was significant at advanced level. It was found that the fathers visiting and supporting their infants in NICUs had the decreased stress levels. It is a useful nursing intervention to support fathers to visit their babies in NICUs and establish environments where they could spend time with their babies.

  12. Chronic mild stress in submissive mice: Marked polydipsia and social avoidance without hedonic deficit in the sucrose preference test.

    PubMed

    Gross, Moshe; Pinhasov, Albert

    2016-02-01

    In the Chronic Mild Stress (CMS) protocol, rodents are exposed to unpredictable stressors to induce anxiety-like behavior and hedonic deficit in the Sucrose Preference test (SPT). Since CMS-induced anxiety- and anhedonic-like behavior may depend upon individual vulnerability to stress, we hypothesized that selectively bred Submissive (Sub) mice would exhibit heightened anxiety- and anhedonic-like behavior, in response to CMS exposure. We anticipated that the testing of Sub mice alongside their Wt counterparts in a battery of behavioral assays would identify parameters most sensitive to CMS effects. To test these assumptions, Sub mice and their outbred Sabra (Wt) counterparts underwent a five-week CMS-SPT regimen. CMS exposure led to reduced preference for sucrose (sucrose-sweetened water as percent of total intake) among both mouse strains (p<0.01 Wt; p<0.05 Sub). However, this effect was attributed to CMS-induced polydipsia, indicated by mice's increased water consumption, (p<0.01 Wt and Sub), without changes in sucrose intake. Furthermore, CMS-exposed Sub mice, but not Wt, demonstrated impaired social exploration in the Three Chamber test (p<0.05) and anxiety-like effects in the Elevated Plus Maze (p<0.05). Moreover, in a separate experiment, social isolation alone was sufficient to induce polydipsia in Sub mice, without affecting Wt mice's drinking behavior. The present findings suggest that the EPM and Three Chamber tests may be valuable complementary measures of CMS effects, alongside the Sucrose Preference test, and introduce the Sub mouse strain for use in study of susceptibility to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Transcriptome dynamics of human pluripotent stem cell-derived contracting cardiomyocytes using an embryoid body model with fetal bovine serum.

    PubMed

    Jung, Kwang Bo; Son, Ye Seul; Lee, Hana; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

    2017-07-25

    Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation. To identify genes, biological processes, and pathways involved in the cardiac differentiation of hPSCs, integrative and comparative analyses of the transcriptome profiles of differentiated CMs from hPSCs and of control CMs of the adult human heart (CM-AHH) were performed using gene ontology, functional annotation clustering, and pathway analyses. Several genes commonly regulated in the differentiated CMs and CM-AHH were enriched in pathways related to cell cycle and nucleotide metabolism. Strikingly, we found that current differentiation protocols did not promote sufficient expression of genes involved in oxidative phosphorylation to differentiate CMs from hPSCs compared to the expression levels in CM-AHH. Therefore, to obtain mature CMs similar to CM-AHH, these deficient pathways in CM differentiation, such as energy-related pathways, must be augmented prior to use for in vitro and in vivo applications. This approach opens up new avenues for facilitating the utilization of hPSC-derived CMs in biomedical research, drug evaluation, and clinical applications for patients with cardiac failure.

  14. Pompe Disease Results in a Golgi-based Glycosylation Deficit in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes*

    PubMed Central

    Raval, Kunil K.; Tao, Ran; White, Brent E.; De Lange, Willem J.; Koonce, Chad H.; Yu, Junying; Kishnani, Priya S.; Thomson, James A.; Mosher, Deane F.; Ralphe, John C.; Kamp, Timothy J.

    2015-01-01

    Infantile-onset Pompe disease is an autosomal recessive disorder caused by the complete loss of lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) activity, which results in lysosomal glycogen accumulation and prominent cardiac and skeletal muscle pathology. The mechanism by which loss of GAA activity causes cardiomyopathy is poorly understood. We reprogrammed fibroblasts from patients with infantile-onset Pompe disease to generate induced pluripotent stem (iPS) cells that were differentiated to cardiomyocytes (iPSC-CM). Pompe iPSC-CMs had undetectable GAA activity and pathognomonic glycogen-filled lysosomes. Nonetheless, Pompe and control iPSC-CMs exhibited comparable contractile properties in engineered cardiac tissue. Impaired autophagy has been implicated in Pompe skeletal muscle; however, control and Pompe iPSC-CMs had comparable clearance rates of LC3-II-detected autophagosomes. Unexpectedly, the lysosome-associated membrane proteins, LAMP1 and LAMP2, from Pompe iPSC-CMs demonstrated higher electrophoretic mobility compared with control iPSC-CMs. Brefeldin A induced disruption of the Golgi in control iPSC-CMs reproduced the higher mobility forms of the LAMPs, suggesting that Pompe iPSC-CMs produce LAMPs lacking appropriate glycosylation. Isoelectric focusing studies revealed that LAMP2 has a more alkaline pI in Pompe compared with control iPSC-CMs due largely to hyposialylation. MALDI-TOF-MS analysis of N-linked glycans demonstrated reduced diversity of multiantennary structures and the major presence of a trimannose complex glycan precursor in Pompe iPSC-CMs. These data suggest that Pompe cardiomyopathy has a glycan processing abnormality and thus shares features with hypertrophic cardiomyopathies observed in the congenital disorders of glycosylation. PMID:25488666

  15. A Novel Cytoplasmic Male Sterility in Brassica napus (inap CMS) with Carpelloid Stamens via Protoplast Fusion with Chinese Woad

    PubMed Central

    Kang, Lei; Li, Pengfei; Wang, Aifan; Ge, Xianhong; Li, Zaiyun

    2017-01-01

    A novel cytoplasmic male sterility (CMS) in Brassica napus (inap CMS) was selected from the somatic hybrid with Isatis indigotica (Chinese woad) by recurrent backcrossing. The male sterility was caused by the conversion of tetradynamous stamens into carpelloid structures with stigmatoid tissues at their tips and ovule-like tissues in the margins, and the two shorter stamens into filaments without anthers. The feminized development of the stamens resulted in the complete lack of pollen grains, which was stable in different years and environments. The pistils of inap CMS displayed normal morphology and good seed-set after pollinated by B. napus. Histological sections showed that the developmental alteration of the stamens initiated at the stage of stamen primordium differentiation. AFLP analysis of the nuclear genomic composition with 23 pairs of selective primers detected no woad DNA bands in inap CMS. Twenty out of 25 mitochondrial genes originated from I. indigotica, except for cox2-2 which was the recombinant between cox2 from woad and cox2-2 from rapeseed. The novel cox2-2 was transcribed in flower buds of inap CMS weakly and comparatively with the fertile B. napus addition line Me harboring one particular woad chromosome. The restorers of other autoplasmic and alloplasmic CMS systems in rapeseed failed to restore the fertility of inap CMS and the screening of B. napus wide resources found no fertility restoration variety, showing its distinct origin and the related mechanism of sterility. The reasons for the mitochondrial rearrangements and the breeding of the restorer for the novel CMS system were discussed. PMID:28428799

  16. Neurodegenerative evidences during early onset of depression in CMS rats as detected by proton magnetic resonance spectroscopy at 7 T.

    PubMed

    Hemanth Kumar, B S; Mishra, Sushanta Kumar; Rana, Poonam; Singh, Sadhana; Khushu, Subash

    2012-06-15

    Depression is a complex psychiatric disorder characterized by anhedonia and feeling of sadness and chronic mild stress (CMS) seems to be a valuable animal model of depression. CMS animal model was induced and validated using behavioral studies. In the present study we investigated the neuro-metabolite changes occurring in prefrontal cortex and hippocampus during the onset of depression, in CMS rat model using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at field strength of 7 T. Results showed that CMS caused depression-like behavior in rats, as indicated by the decrease in sucrose consumption and locomotor activity. (1)H MRS was performed in both control and CMS rats (n=10, in each group) and the quantitative assessment of the neurometabolites was done using LC model. Relative concentrations of all the metabolites along with the macromolecules were calculated for analysis. The results revealed a significant decrease of glutamate (Glu), glutamine (Gln), NAA+NAAG, Glx and GABA levels in both hippocampus and prefrontal cortex of CMS animals and an elevated level of myo-ionisitol (mI) and taurine (Tau) was observed only in hippocampus. These metabolite fluctuations revealed by proton MRS indicate that there might be change in the neuronal integrity of the glial cells and neurons within prefrontal cortex and hippocampus in CMS model of depression. The present study also suggests that there may be a degenerative process concerning the brain morphology in the CMS rats. The overall finding using (1)H MRS suggests that, there might be a major role of the glia and neuron in the onset of depression. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Effect of priming cooperation or individualism on a collective and interdependent task: changeover speed in the 4 x 100-meter relay race.

    PubMed

    Bry, Clémentine; Meyer, Thierry; Oberlé, Dominique; Gherson, Thibault

    2009-06-01

    Priming effects of cooperation vs. individualism were investigated on changeover speed within a 4 x 100-m relay race. Ten teams of four adult beginner athletes ran two relays, a pretest race and an experimental race 3 weeks later. Just before the experimental race, athletes were primed with either cooperation or individualism through a scrambled-sentence task. Comparing to the pretest performance, cooperation priming improved baton speed in the exchange zone (+30 cm/s). Individualism priming did not impair changeover performance. The boundary conditions of priming effects applied to collective and interdependent tasks are discussed within the implicit coordination framework.

  18. Hospitals push back against reimbursement cuts due to Two-Midnight rule.

    PubMed

    2016-04-01

    The American Hospital Association (AHA) and other hospitals are suing CMS, challenging the 0.2% cut in Medicare reimbursement that CMS instituted to compensate for the financial effect of the Two-Midnight rule. CMS' actuaries reported that inpatient claims are likely to increase under the rule, resulting in $220 million additional reimbursement for hospitals. Hospitals disagree and a study commissioned by the AHA concluded that the CMS study was based on data not available to the public and that data from the Medicare Provider and Analysis Review (MedPAR) would lead to a different conclusion. The AHA suit asks CMS to rescind the cut, restore the base rate for Medicare payments to its previous level, and reimburse hospitals retroactively for the reductions.

  19. User and group storage management the CMS CERN T2 centre

    NASA Astrophysics Data System (ADS)

    Cerminara, G.; Franzoni, G.; Pfeiffer, A.

    2015-12-01

    A wide range of detector commissioning, calibration and data analysis tasks is carried out by CMS using dedicated storage resources available at the CMS CERN Tier-2 centre. Relying on the functionalities of the EOS disk-only storage technology, the optimal exploitation of the CMS user/group resources has required the introduction of policies for data access management, data protection, cleanup campaigns based on access pattern, and long term tape archival. The resource management has been organised around the definition of working groups and the delegation to an identified responsible of each group composition. In this paper we illustrate the user/group storage management, and the development and operational experience at the CMS CERN Tier-2 centre in the 2012-2015 period.

  20. 45 CFR 150.219 - Final determination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States... substantially enforce, CMS finds that the failure to substantially enforce has not been corrected, it will send...

  1. 45 CFR 150.215 - Extension for good cause.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.215 Extension for good cause. CMS may...

  2. 45 CFR 150.217 - Preliminary determination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States... the end of the 30-day period (and any extension), the State has not established to CMS's satisfaction...

  3. The anti-CMS technique for genome-wide mapping of 5-hydroxymethylcytosine.

    PubMed

    Huang, Yun; Pastor, William A; Zepeda-Martínez, Jorge A; Rao, Anjana

    2012-10-01

    5-Hydroxymethylcytosine (5hmC) is a recently discovered base in the mammalian genome, produced upon oxidation of 5-methylcytosine (5mC) in a process catalyzed by TET proteins. The biological functions of 5hmC and further oxidation products of 5mC are under intense investigation, as they are likely intermediates in DNA demethylation pathways. Here we describe a novel protocol to profile 5hmC at a genome-wide scale. This approach is based on sodium bisulfite-mediated conversion of 5hmC to cytosine-5-methylenesulfonate (CMS); CMS-containing DNA fragments are then immunoprecipitated using a CMS-specific antiserum. The anti-CMS technique is highly specific with a low background, and is much less dependent on 5hmC density than anti-5hmC immunoprecipitation (IP). Moreover, it does not enrich for CA and CT repeats, as noted for 5hmC DNA IP using antibodies to 5hmC. The anti-CMS protocol takes 3 d to complete.

  4. The chronic mild stress (CMS) model of depression: History, evaluation and usage.

    PubMed

    Willner, Paul

    2017-02-01

    Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

  5. Leveraging the big-data revolution: CMS is expanding capabilities to spur health system transformation.

    PubMed

    Brennan, Niall; Oelschlaeger, Allison; Cox, Christine; Tavenner, Marilyn

    2014-07-01

    As the largest single payer for health care in the United States, the Centers for Medicare and Medicaid Services (CMS) generates enormous amounts of data. Historically, CMS has faced technological challenges in storing, analyzing, and disseminating this information because of its volume and privacy concerns. However, rapid progress in the fields of data architecture, storage, and analysis--the big-data revolution--over the past several years has given CMS the capabilities to use data in new and innovative ways. We describe the different types of CMS data being used both internally and externally, and we highlight a selection of innovative ways in which big-data techniques are being used to generate actionable information from CMS data more effectively. These include the use of real-time analytics for program monitoring and detecting fraud and abuse and the increased provision of data to providers, researchers, beneficiaries, and other stakeholders. Project HOPE—The People-to-People Health Foundation, Inc.

  6. Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy.

    PubMed

    Cho, Gun-Sik; Lee, Dong I; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Chen, Huei-Sheng Vincent; Chen, Xiongwen; Basso, Cristina; Houser, Steven R; Tomaselli, Gordon F; O'Rourke, Brian; Judge, Daniel P; Kass, David A; Kwon, Chulan

    2017-01-10

    Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

    PubMed Central

    Cho, Gun-Sik; Lee, Dong I.; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Vincent Chen, Huei-Sheng; Chen, Xiongwen; Basso, Cristina; Houser, Steven R.; Tomaselli, Gordon F.; O’Rourke, Brian; Judge, Daniel P.; Kass, David A.; Kwon, Chulan

    2016-01-01

    SUMMARY Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of the transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which predominantly manifests in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. PMID:28076798

  8. China's Rural Cooperative Medical Scheme: a type of health insurance or a type of health cooperative?

    PubMed

    Wang, Fang; Liang, Yuan

    2017-03-01

    The Cooperative Medical Scheme (CMS) was popular in rural China in the 1960s and 1970s, having garnered praise from the World Bank and World Health Organization as an unprecedented example of a successful health care model in a low-income developing country. However, the CMS almost collapsed in the 1980s. Based on its historical origins and main activities, we think the CMS functioned as a health cooperative rather than a health insurance scheme. Perhaps, however, the importance to the CMS of cooperation between institutions has been overestimated. Overlooked, yet equally important, has been the cooperation between health workers and farmers to target health-related risk factors associated with agricultural work and ways of life. The 'cooperative' character of the CMS includes two aspects: cooperative institutions and cooperative behaviour. Although the CMS collapsed in China, similar schemes are flourishing elsewhere in the world. In the future, in-depth analysis of these schemes is required.

  9. Simulation of strong ground motion parameters of the 1 June 2013 Gulf of Suez earthquake, Egypt

    NASA Astrophysics Data System (ADS)

    Toni, Mostafa

    2017-06-01

    This article aims to simulate the ground motion parameters of the moderate magnitude (ML 5.1) June 1, 2013 Gulf of Suez earthquake, which represents the largest instrumental earthquake to be recorded in the middle part of the Gulf of Suez up to now. This event was felt in all cities located on both sides of the Gulf of Suez, with minor damage to property near the epicenter; however, no casualties were observed. The stochastic technique with the site-dependent spectral model is used to simulate the strong ground motion parameters of this earthquake in the cities located at the western side of the Gulf of Suez and north Red Sea namely: Suez, Ain Sokhna, Zafarana, Ras Gharib, and Hurghada. The presence of many tourist resorts and the increase in land use planning in the considered cities represent the motivation of the current study. The simulated parameters comprise the Peak Ground Acceleration (PGA), Peak Ground Velocity (PGV), and Peak Ground Displacement (PGD), in addition to Pseudo Spectral Acceleration (PSA). The model developed for ground motion simulation is validated by using the recordings of three accelerographs installed around the epicenter of the investigated earthquake. Depending on the site effect that has been determined in the investigated areas by using geotechnical data (e.g., shear wave velocities and microtremor recordings), the investigated areas are classified into two zones (A and B). Zone A is characterized by higher site amplification than Zone B. The ground motion parameters are simulated at each zone in the considered areas. The results reveal that the highest values of PGA, PGV, and PGD are observed at Ras Gharib city (epicentral distance ∼ 11 km) as 67 cm/s2, 2.53 cm/s, and 0.45 cm respectively for Zone A, and as 26.5 cm/s2, 1.0 cm/s, and 0.2 cm respectively for Zone B, while the lowest values of PGA, PGV, and PGD are observed at Suez city (epicentral distance ∼ 190 km) as 3.0 cm/s2, 0.2 cm/s, and 0.05 cm/s respectively for Zone A, and as 1.3 cm/s2, 0.1 cm/s, and 0.024 cm respectively for Zone B. Also the highest PSA values are observed in Ras Gharib city as 200 cm/s2 and 78 cm/s2 for Zone A and Zone B respectively, while the lowest PSA values are observed in Suez city as 7 cm/s2 and 3 cm/s2 for Zone A and Zone B respectively. These results show a good agreement with the earthquake magnitude, epicentral distances, and site characterizations as well.

  10. Effect of investigator disturbance in experimental forensic entomology: succession and community composition.

    PubMed

    De Jong, G D; Hoback, W W

    2006-06-01

    Carrion insect succession studies have historically used repeated sampling of single or a few carcasses to produce data, either weighing the carcasses, removing a qualitative subsample of the fauna present, or both, on every visit over the course of decomposition and succession. This study, conducted in a set of related experimental hypotheses with two trials in a single season, investigated the effect that repeated sampling has on insect succession, determined by the number of taxa collected on each visit and by community composition. Each trial lasted at least 21 days, with daily visits on the first 14 days. Rat carcasses used in this study were all placed in the field on the same day, but then either sampled qualitatively on every visit (similar to most succession studies) or ignored until a given day of succession, when they were sampled qualitatively (a subsample) and then destructively sampled in their entirety. Carcasses sampled on every visit were in two groups: those from which only a sample of the fauna was taken and those from which a sample of fauna was taken and the carcass was weighed for biomass determination. Of the carcasses visited only once, the number of taxa in subsamples was compared to the actual number of taxa present when the carcass was destructively sampled to determine if the subsamples adequately represented the total carcass fauna. Data from the qualitative subsamples of those carcasses visited only once were also compared to data collected from carcasses that were sampled on every visit to investigate the effect of the repeated sampling. A total of 39 taxa were collected from carcasses during the study and the component taxa are discussed individually in relation to their role in succession. Number of taxa differed on only one visit between the qualitative subsamples and the actual number of taxa present, primarily because the organisms missed by the qualitative sampling were cryptic (hidden deep within body cavities) or rare (only represented by very few specimens). There were no differences discovered between number of taxa in qualitative subsamples from carcasses sampled repeatedly (with or without biomass determinations) and those sampled only a single time. Community composition differed considerably in later stages of decomposition, with disparate communities due primarily to small numbers of rare taxa. These results indicate that the methods used historically for community composition determination in experimental forensic entomology are generally adequate.

  11. Proarrhythmia risk prediction using human induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Yamazaki, Daiju; Kitaguchi, Takashi; Ishimura, Masakazu; Taniguchi, Tomohiko; Yamanishi, Atsuhiro; Saji, Daisuke; Takahashi, Etsushi; Oguchi, Masao; Moriyama, Yuta; Maeda, Sanae; Miyamoto, Kaori; Morimura, Kaoru; Ohnaka, Hiroki; Tashibu, Hiroyuki; Sekino, Yuko; Miyamoto, Norimasa; Kanda, Yasunari

    2018-04-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and drug responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs and Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays in iCell-CMs, it has not been fully understood an availability of Cor.4U-CMs for proarrhythmia risk. Here, we evaluated the predictivity of proarrhythmia risk using Cor.4U-CMs. MEA assay revealed linear regression between inter-spike interval and field potential duration (FPD). The hERG inhibitor E-4031 induced reverse-use dependent FPD prolongation. We next evaluated the proarrhythmia risk prediction by a two-dimensional map, which we have previously proposed. We determined the relative torsade de pointes risk score, based on the extent of FPD with Fridericia's correction (FPDcF) change and early afterdepolarization occurrence, and calculated the margins normalized to free effective therapeutic plasma concentrations. The drugs were classified into three risk groups using the two-dimensional map. This risk-categorization system showed high concordance with the torsadogenic information obtained by a public database CredibleMeds. Taken together, these results indicate that Cor.4U-CMs can be used for drug-induced proarrhythmia risk prediction. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  12. Risk factors for covered metallic stent migration in patients with distal malignant biliary obstruction due to pancreatic cancer.

    PubMed

    Nakai, Yousuke; Isayama, Hiroyuki; Kogure, Hirofumi; Hamada, Tsuyoshi; Togawa, Osamu; Ito, Yukiko; Matsubara, Saburo; Arizumi, Toshihiko; Yagioka, Hiroshi; Mizuno, Suguru; Sasaki, Takashi; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

    2014-09-01

    Covered metallic stents (CMSs) were developed to overcome tumor ingrowth in uncovered metallic stents (UMSs) for malignant biliary obstruction, but superiority of CMSs over UMSs is still controversial due to the high migration rate in CMS. Therefore, we conducted this retrospective analysis to clarify risk factors for stent migration, including mechanical properties of CMSs. Patients with unresectable pancreatic cancer, receiving CMS for distal malignant biliary obstruction in five tertiary care centers, were retrospectively studied. Univariate and multivariate analyses to identify prognostic factors for early (< 6 months) stent migration were performed using a proportional hazards model with death or stent occlusion without stent migration as a competing risk. Two mechanical properties were included in the analysis: axial force, the recovery force that leads to a CMS straightening, and radial force (RF), the expansion force against the stricture. Among 290 patients who received CMS placement for distal malignant biliary obstruction, stent migration rate was 15.2%. CMS migrated early (< 6 months) in 10.0% and distally in 11.7%, respectively. In the multivariate analysis, significant risk factors for early stent migration were chemotherapy (subdistribution hazard ratios [SHR] 4.46, P = 0.01), CMS with low RF (SHR 2.23, P = 0.03), and duodenal invasion (SHR 2.25, P = 0.02). CMS with low RF, chemotherapy, and duodenal invasion were associated with CMS migration from our study. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. Neuropsychological function in children with primary complex motor stereotypies.

    PubMed

    Mahone, E Mark; Ryan, Matthew; Ferenc, Lisa; Morris-Berry, Christina; Singer, Harvey S

    2014-10-01

    Complex motor stereotypies (CMS) are patterned, repetitive, rhythmic, and involuntary movements that persist over time. They are divided into two subgroups dependent on the presence of other developmental problems: 'primary' (development is otherwise typical) or 'secondary' (associated with autism, intellectual disability, or sensory deficits). There are no currently published studies that examine neuropsychological function in children with primary CMS. This case-control study examines whether children with primary CMS manifest neurobehavioral deficits. Fifty-seven children with primary CMS (32 males, 25 females; mean age 6y 8mo, SD 2y 4mo, range 4-12y) with negative screens for autism and 57 comparison participants (32 males, 25 females; mean age 6y 6mo, SD 2y 1mo) completed neuropsychological assessments of IQ, reading ability, attention, language, and motor and executive functions. Parents completed ratings of their child's repetitive movement severity. The CMS group performed significantly less well than comparison participants on motor skills and IQ tests (both p<0.01), although IQ was consistently in the average range. One-third of the CMS group showed signs of developmental motor coordination difficulties. Parent report of stereotypy severity was significantly associated with parent report of inattention and executive dysfunction. Children with primary CMS were found to have largely intact neuropsychological profiles. Stereotypy severity appears to be associated with executive dysfunction. Although motor difficulties were observed in children with CMS, these were not correlated with parent report of symptom severity. © 2014 Mac Keith Press.

  14. Large scale commissioning and operational experience with tier-2 to tier-2 data transfer links in CMS

    NASA Astrophysics Data System (ADS)

    Letts, J.; Magini, N.

    2011-12-01

    Tier-2 to Tier-2 data transfers have been identified as a necessary extension of the CMS computing model. The Debugging Data Transfers (DDT) Task Force in CMS was charged with commissioning Tier-2 to Tier-2 PhEDEx transfer links beginning in late 2009, originally to serve the needs of physics analysis groups for the transfer of their results between the storage elements of the Tier-2 sites associated with the groups. PhEDEx is the data transfer middleware of the CMS experiment. For analysis jobs using CRAB, the CMS Remote Analysis Builder, the challenges of remote stage out of job output at the end of the analysis jobs led to the introduction of a local fallback stage out, and will eventually require the asynchronous transfer of user data over essentially all of the Tier-2 to Tier-2 network using the same PhEDEx infrastructure. In addition, direct file sharing of physics and Monte Carlo simulated data between Tier-2 sites can relieve the operational load of the Tier-1 sites in the original CMS Computing Model, and already represents an important component of CMS PhEDEx data transfer volume. The experience, challenges and methods used to debug and commission the thousands of data transfers links between CMS Tier-2 sites world-wide are explained and summarized. The resulting operational experience with Tier-2 to Tier-2 transfers is also presented.

  15. Development of a Sensitive and Specific Polyclonal Antibody for Serological Detection of Clavibacter michiganensis subsp. sepedonicus

    PubMed Central

    Przewodowska, Agnieszka

    2017-01-01

    The quarantine bacterium Clavibacter michiganensis subsp. sepedonicus (Cms) causes bacterial ring rot (BRR) in potato but is difficult to detect, hampering the diagnosis of this disease. ELISA immunoassays have not been widely used to detect Cms because commercially available anti-Cms antibodies detect mainly EPS-producing bacteria and can fail to detect strains that do not produce EPS. In the current study, we developed a new type of polyclonal antibody that specifically detects Clavibacter michiganensis subsp. sepedonicus bacteria irrespective of their EPS level. We first found that the presence of bacterial EPS precluded quantitative measurement of bacteria by currently available immunoenzymatic methods, but that washing Cms cells with acidic and basic buffers to remove EPS before analysis successfully standardized ELISA results. We used a mix of three strains of Cms with diverse EPS levels to generate antigen for production of antibodies recognizing Cms cells with and without an EPS layer (IgG-EPS and IgG-N-EPS, respectively). The resulting IgG-N-EPS recognized almost all Cms strains tested in this work regardless of their mucoidal level. The availability of this new antibody renders immunological diagnostics of Cms more sensitive and reliable, as our newly developed antibodies can be used in many type of immunoassays. This work represents an important step forward in efforts to diagnose and prevent the spread of BRR, and the methods and solutions developed in this work are covered by six Polish, one European and one US patents. PMID:28068400

  16. 78 FR 62636 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... the following transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk... Identifiers: CMS-10486] Agency Information Collection Activities: Submission for OMB Review; Comment Request... for the public to comment on CMS' intention to collect information from the public. Under the...

  17. 23 CFR 970.214 - Federal lands congestion management system (CMS).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Federal lands congestion management system (CMS). 970... LANDS HIGHWAYS NATIONAL PARK SERVICE MANAGEMENT SYSTEMS National Park Service Management Systems § 970.214 Federal lands congestion management system (CMS). (a) For purposes of this section, congestion...

  18. 42 CFR 422.210 - Assurances to CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Assurances to CMS. 422.210 Section 422.210 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Relationships With Providers § 422.210 Assurances to CMS. (a...

  19. Proteomic Analysis of Male-Fertility Restoration in CMS Onion

    USDA-ARS?s Scientific Manuscript database

    The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using proteomics ...

  20. 78 FR 78970 - Emergency Clearance: Public Information Collection Requirements Submitted to the Office of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... Identifier: CMS-10510] Emergency Clearance: Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS..., Federal Register notice (document identifier: CMS-10510) entitled ``Basic Health Program Report for Health...

  1. 45 CFR 150.459 - Judicial review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS...) Simultaneously sending a copy of the notice of appeal by registered mail to CMS. (b) Certification of administrative record. CMS promptly certifies and files with the court the record upon which the penalty was...

  2. 45 CFR 150.211 - Notice to the State.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.211 Notice to the State. If CMS is...

  3. 42 CFR 422.157 - Accreditation organizations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

  4. 42 CFR 422.157 - Accreditation organizations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

  5. 42 CFR 422.157 - Accreditation organizations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

  6. CompHEP: developments and applications

    NASA Astrophysics Data System (ADS)

    Boos, E. E.; Bunichev, V. E.; Dubinin, M. N.; Ilyin, V. A.; Savrin, V. I.; CompHEP Collaboration

    2017-11-01

    New developments of the CompHEP package and its applications to the top quark and the Higgs boson physics at the LHC collider are reviewed. These developments were motivated mainly by the needs of experimental searches of DO (Tevatron) and CMS (LHC) collaborations where identification of the top quark and the Higgs boson in the framework of the Standard Model (SM) or possible extensions of the SM played an important role. New useful features of the CompHEP Graphics User Interface (GUI) are described.

  7. Parent Involvement Affects Children's Cognitive Growth.

    ERIC Educational Resources Information Center

    Irvine, David J.; And Others

    As part of a longitudinal study of the New York State Experimental Prekindergarten Program, the effect of degree of parental involvement in the program on children's cognitive development was examined. Parent involvement included employment in the program, school visits, home visits by school personnel, group meetings, and incidental contacts such…

  8. 47 CFR 10.230 - New CMS providers participation in CMAS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false New CMS providers participation in CMAS. 10.230 Section 10.230 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Election to Participate in Commercial Mobile Alert System § 10.230 New CMS providers participation in CMAS...

  9. 76 FR 35444 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ... retrieval into the ASPEN system. The information needed to make certification decisions is available to CMS... Identifier CMS-1856 and CMS-1893] Agency Information Collection Activities: Submission for OMB Review... or any other aspect of this collection of information, including any of the following subjects: (1...

  10. 78 FR 42778 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-17

    ... transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk Officer, Fax Number: (202... Identifier: CMS-10494] Agency Information Collection Activities: Submission for OMB Review; Comment Request... for the public to comment on CMS' intention to collect information from the public. Under the...

  11. 78 FR 71617 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... the following transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk... Identifier: CMS-R-194] Agency Information Collection Activities: Submission for OMB Review; Comment Request... for the public to comment on CMS' intention to collect information from the public. Under the...

  12. 78 FR 40482 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk Officer, Fax Number: (202... Identifier: CMS-10316] Agency Information Collection Activities: Submission for OMB Review; Comment Request... for the public to comment on CMS' intention to collect information from the public. Under the...

  13. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) CMS notifies the MA organization in writing at least 45 calendar days before the intended date of the...; or (B) The MA organization experiences financial difficulties so severe that its ability to make...)(i) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

  14. 78 FR 39296 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... & Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect information from the public. Under the Paperwork Reduction Act of 1995 (PRA), federal agencies are required to... Identifier: CMS-10486] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY...

  15. 42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

  16. 77 FR 52035 - Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-28

    ... Identifier: CMS-10003] Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Correction of notice. SUMMARY: This document corrects a technical error in the notice [Document Identifier: CMS...

  17. 45 CFR 150.309 - Request for extension.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and Non-Federal... cannot prepare a response to CMS within the 30 days provided in the notice, the entity may make a written...

  18. 76 FR 33305 - Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... Identifier: CMS-10379] Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Correction of notice. SUMMARY: This document corrects the information provided for [Document Identifier: CMS...

  19. 42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

  20. 42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

  1. 42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

  2. 42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

  3. Ada (Tradename) Compiler Validation Summary Report. International Business Machines Corporation. IBM Development System for the Ada Language for VM/CMS, Version 1.0. IBM 4381 (IBM System/370) under VM/CMS.

    DTIC Science & Technology

    1986-04-29

    COMPILER VALIDATION SUMMARY REPORT: International Business Machines Corporation IBM Development System for the Ada Language for VM/CMS, Version 1.0 IBM 4381...tested using command scripts provided by International Business Machines Corporation. These scripts were reviewed by the validation team. Test.s were run...s): IBM 4381 (System/370) Operating System: VM/CMS, release 3.6 International Business Machines Corporation has made no deliberate extensions to the

  4. The CMS Data Analysis School Experience

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

    De Filippis, N.; Bauerdick, L.; Chen, J.

    The CMS Data Analysis School is an official event organized by the CMS Collaboration to teach students and post-docs how to perform a physics analysis. The school is coordinated by the CMS schools committee and was first implemented at the LHC Physics Center at Fermilab in 2010. As part of the training, there are a number of “short” exercises on physics object reconstruction and identification, Monte Carlo simulation, and statistical analysis, which are followed by “long” exercises based on physics analyses. Some of the long exercises go beyond the current state of the art of the corresponding CMS analyses. Thismore » paper describes the goals of the school, the preparations for a school, the structure of the training, and student satisfaction with the experience as measured by surveys.« less

  5. The CMS data analysis school experience

    NASA Astrophysics Data System (ADS)

    De Filippis, N.; Bauerdick, L.; Chen, J.; Gallo, E.; Klima, B.; Malik, S.; Mulders, M.; Palla, F.; Rolandi, G.

    2017-10-01

    The CMS Data Analysis School is an official event organized by the CMS Collaboration to teach students and post-docs how to perform a physics analysis. The school is coordinated by the CMS schools committee and was first implemented at the LHC Physics Center at Fermilab in 2010. As part of the training, there are a number of “short” exercises on physics object reconstruction and identification, Monte Carlo simulation, and statistical analysis, which are followed by “long” exercises based on physics analyses. Some of the long exercises go beyond the current state of the art of the corresponding CMS analyses. This paper describes the goals of the school, the preparations for a school, the structure of the training, and student satisfaction with the experience as measured by surveys.

  6. Cytoplasmic male sterility-associated chimeric open reading frames identified by mitochondrial genome sequencing of four Cajanus genotypes.

    PubMed

    Tuteja, Reetu; Saxena, Rachit K; Davila, Jaime; Shah, Trushar; Chen, Wenbin; Xiao, Yong-Li; Fan, Guangyi; Saxena, K B; Alverson, Andrew J; Spillane, Charles; Town, Christopher; Varshney, Rajeev K

    2013-10-01

    The hybrid pigeonpea (Cajanus cajan) breeding technology based on cytoplasmic male sterility (CMS) is currently unique among legumes and displays major potential for yield increase. CMS is defined as a condition in which a plant is unable to produce functional pollen grains. The novel chimeric open reading frames (ORFs) produced as a results of mitochondrial genome rearrangements are considered to be the main cause of CMS. To identify these CMS-related ORFs in pigeonpea, we sequenced the mitochondrial genomes of three C. cajan lines (the male-sterile line ICPA 2039, the maintainer line ICPB 2039, and the hybrid line ICPH 2433) and of the wild relative (Cajanus cajanifolius ICPW 29). A single, circular-mapping molecule of length 545.7 kb was assembled and annotated for the ICPA 2039 line. Sequence annotation predicted 51 genes, including 34 protein-coding and 17 RNA genes. Comparison of the mitochondrial genomes from different Cajanus genotypes identified 31 ORFs, which differ between lines within which CMS is present or absent. Among these chimeric ORFs, 13 were identified by comparison of the related male-sterile and maintainer lines. These ORFs display features that are known to trigger CMS in other plant species and to represent the most promising candidates for CMS-related mitochondrial rearrangements in pigeonpea.

  7. Validation and Application of a Real-time PCR Protocol for the Specific Detection and Quantification of Clavibacter michiganensis subsp. sepedonicus in Potato.

    PubMed

    Cho, Min Seok; Park, Duck Hwan; Namgung, Min; Ahn, Tae-Young; Park, Dong Suk

    2015-06-01

    Clavibacter michiganensis subsp. sepedonicus (Cms) multiplies very rapidly, passing through the vascular strands and into the stems and petioles of a diseased potato. Therefore, the rapid and specific detection of this pathogen is highly important for the effective control of the pathogen. Although several PCR assays have been developed for detection, they cannot afford specific detection of Cms. Therefore, in this study, a computational genome analysis was performed to compare the sequenced genomes of the C. michiganensis subspecies and to identify an appropriate gene for the development of a subspecies-specific PCR primer set (Cms89F/R). The specificity of the primer set based on the putative phage-related protein was evaluated using genomic DNA from seven isolates of Cms and 27 other reference strains. The Cms89F/R primer set was more specific and sensitive than the existing assays in detecting Cms in in vitro using Cms cells and its genomic DNA. This assay was also able to detect at least 1.47×10(2) copies/μl of cloned-amplified target DNA, 5 fg of DNA using genomic DNA or 10(-6) dilution point of 0.12 at OD600 units of cells per reaction using a calibrated cell suspension.

  8. Cytoplasmic Male Sterility-Associated Chimeric Open Reading Frames Identified by Mitochondrial Genome Sequencing of Four Cajanus Genotypes

    PubMed Central

    Tuteja, Reetu; Saxena, Rachit K.; Davila, Jaime; Shah, Trushar; Chen, Wenbin; Xiao, Yong-Li; Fan, Guangyi; Saxena, K. B.; Alverson, Andrew J.; Spillane, Charles; Town, Christopher; Varshney, Rajeev K.

    2013-01-01

    The hybrid pigeonpea (Cajanus cajan) breeding technology based on cytoplasmic male sterility (CMS) is currently unique among legumes and displays major potential for yield increase. CMS is defined as a condition in which a plant is unable to produce functional pollen grains. The novel chimeric open reading frames (ORFs) produced as a results of mitochondrial genome rearrangements are considered to be the main cause of CMS. To identify these CMS-related ORFs in pigeonpea, we sequenced the mitochondrial genomes of three C. cajan lines (the male-sterile line ICPA 2039, the maintainer line ICPB 2039, and the hybrid line ICPH 2433) and of the wild relative (Cajanus cajanifolius ICPW 29). A single, circular-mapping molecule of length 545.7 kb was assembled and annotated for the ICPA 2039 line. Sequence annotation predicted 51 genes, including 34 protein-coding and 17 RNA genes. Comparison of the mitochondrial genomes from different Cajanus genotypes identified 31 ORFs, which differ between lines within which CMS is present or absent. Among these chimeric ORFs, 13 were identified by comparison of the related male-sterile and maintainer lines. These ORFs display features that are known to trigger CMS in other plant species and to represent the most promising candidates for CMS-related mitochondrial rearrangements in pigeonpea. PMID:23792890

  9. Validation and Application of a Real-time PCR Protocol for the Specific Detection and Quantification of Clavibacter michiganensis subsp. sepedonicus in Potato

    PubMed Central

    Cho, Min Seok; Park, Duck Hwan; Namgung, Min; Ahn, Tae-Young; Park, Dong Suk

    2015-01-01

    Clavibacter michiganensis subsp. sepedonicus (Cms) multiplies very rapidly, passing through the vascular strands and into the stems and petioles of a diseased potato. Therefore, the rapid and specific detection of this pathogen is highly important for the effective control of the pathogen. Although several PCR assays have been developed for detection, they cannot afford specific detection of Cms. Therefore, in this study, a computational genome analysis was performed to compare the sequenced genomes of the C. michiganensis subspecies and to identify an appropriate gene for the development of a subspecies-specific PCR primer set (Cms89F/R). The specificity of the primer set based on the putative phage-related protein was evaluated using genomic DNA from seven isolates of Cms and 27 other reference strains. The Cms89F/R primer set was more specific and sensitive than the existing assays in detecting Cms in in vitro using Cms cells and its genomic DNA. This assay was also able to detect at least 1.47×102 copies/μl of cloned-amplified target DNA, 5 fg of DNA using genomic DNA or 10−6 dilution point of 0.12 at OD600 units of cells per reaction using a calibrated cell suspension. PMID:26060431

  10. Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells

    PubMed Central

    Han, Lu; Li, Yang; Tchao, Jason; Kaplan, Aaron D.; Lin, Bo; Li, You; Mich-Basso, Jocelyn; Lis, Agnieszka; Hassan, Narmeen; London, Barry; Bett, Glenna C.L.; Tobita, Kimimasa; Rasmusson, Randall L.; Yang, Lei

    2014-01-01

    Aims Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies. Methods and results To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for ‘Cell Proliferation’ was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments. Conclusion Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases. PMID:25209314

  11. Cardiomyopathy syndrome in Atlantic salmon Salmo salar L.: A review of the current state of knowledge.

    PubMed

    Garseth, Å H; Fritsvold, C; Svendsen, J C; Bang Jensen, B; Mikalsen, A B

    2018-01-01

    Cardiomyopathy syndrome (CMS) is a severe cardiac disease affecting Atlantic salmon Salmo salar L. The disease was first recognized in farmed Atlantic salmon in Norway in 1985 and subsequently in farmed salmon in the Faroe Islands, Scotland and Ireland. CMS has also been described in wild Atlantic salmon in Norway. The demonstration of CMS as a transmissible disease in 2009, and the subsequent detection and initial characterization of piscine myocarditis virus (PMCV) in 2010 and 2011 were significant discoveries that gave new impetus to the CMS research. In Norway, CMS usually causes mortality in large salmon in ongrowing and broodfish farms, resulting in reduced fish welfare, significant management-related challenges and substantial economic losses. The disease thus has a significant impact on the Atlantic salmon farming industry. There is a need to gain further basic knowledge about the virus, the disease and its epidemiology, but also applied knowledge from the industry to enable the generation and implementation of effective prevention and control measures. This review summarizes the currently available, scientific information on CMS and PMCV with special focus on epidemiology and factors influencing the development of CMS. © 2017 The Authors. Journal of Fish Diseases Published by John Wiley & Sons Ltd.

  12. Gas separation performance of carbon molecular sieve membranes based on 6FDA-mPDA/DABA (3:2) polyimide.

    PubMed

    Qiu, Wulin; Zhang, Kuang; Li, Fuyue Stephanie; Zhang, Ke; Koros, William J

    2014-04-01

    6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO2 /CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

    NASA Astrophysics Data System (ADS)

    Gao, Ziyang

    Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of cellular solids and make substantial contributions to the theoretical advance of impact dynamics.

  14. Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes

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

    Lee, Sujeong, E-mail: crystalee@gmail.com; Lee, Hyang-Ae, E-mail: hyangaelee@gmail.com; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799

    2016-04-01

    The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effectsmore » of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD{sub 90}) and 50% (APD{sub 50}) repolarization, reduced the maximum upstroke velocity (dV/dt{sub max}) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including I{sub Kr}, I{sub Ks}, I{sub Na}, and I{sub Ca}. Among them, I{sub Kr} and I{sub Na} showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K{sup +} channels. - Highlights: • Nefazodone prolonged APD and decreased upstroke velocity of APs in hiPSC-CMs. • Nefazodone inhibited cardiac ion channels, especially I{sub Kr} and I{sub Na}, in hiPSC-CMs. • Nefazodone-induced AP changes are mainly the result of I{sub Kr} and I{sub Na} inhibition. • hiPSC-CMs are sensitive model to validate nefazodone-induced cardiotoxicity. • hiPSC-CMs provide an integrated approach for evaluating mechanism of drug actions.« less

  15. Toward Personalized Medicine: Using Cardiomyocytes Differentiated From Urine-Derived Pluripotent Stem Cells to Recapitulate Electrophysiological Characteristics of Type 2 Long QT Syndrome.

    PubMed

    Jouni, Mariam; Si-Tayeb, Karim; Es-Salah-Lamoureux, Zeineb; Latypova, Xenia; Champon, Benoite; Caillaud, Amandine; Rungoat, Anais; Charpentier, Flavien; Loussouarn, Gildas; Baró, Isabelle; Zibara, Kazem; Lemarchand, Patricia; Gaborit, Nathalie

    2015-09-01

    Human genetically inherited cardiac diseases have been studied mainly in heterologous systems or animal models, independent of patients' genetic backgrounds. Because sources of human cardiomyocytes (CMs) are extremely limited, the use of urine samples to generate induced pluripotent stem cell-derived CMs would be a noninvasive method to identify cardiac dysfunctions that lead to pathologies within patients' specific genetic backgrounds. The objective was to validate the use of CMs differentiated from urine-derived human induced pluripotent stem (UhiPS) cells as a new cellular model for studying patients' specific arrhythmia mechanisms. Cells obtained from urine samples of a patient with long QT syndrome who harbored the HERG A561P gene mutation and his asymptomatic noncarrier mother were reprogrammed using the episomal-based method. UhiPS cells were then differentiated into CMs using the matrix sandwich method.UhiPS-CMs showed proper expression of atrial and ventricular myofilament proteins and ion channels. They were electrically functional, with nodal-, atrial- and ventricular-like action potentials recorded using high-throughput optical and patch-clamp techniques. Comparison of HERG expression from the patient's UhiPS-CMs to the mother's UhiPS-CMs showed that the mutation led to a trafficking defect that resulted in reduced delayed rectifier K(+) current (IKr). This phenotype gave rise to action potential prolongation and arrhythmias. UhiPS cells from patients carrying ion channel mutations can be used as novel tools to differentiate functional CMs that recapitulate cardiac arrhythmia phenotypes. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations.

    PubMed

    Guergueltcheva, Velina; Müller, Juliane S; Dusl, Marina; Senderek, Jan; Oldfors, Anders; Lindbergh, Christopher; Maxwell, Susan; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Vilchez, Juan J; Muelas, Nuria; Kirschner, Janbernd; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P; Schlotter, Beate; Schoser, Benedikt; Herrmann, Ralf; Voit, Thomas; Steinlein, Ortrud K; Najafi, Abdolhamid; Urtizberea, Andoni; Soler, Doriette M; Muntoni, Francesco; Hanna, Michael G; Chaouch, Amina; Straub, Volker; Bushby, Kate; Palace, Jacqueline; Beeson, David; Abicht, Angela; Lochmüller, Hanns

    2012-05-01

    Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).

  17. The Church Mountain Sturzstrom (Mega-Landslide), Glacier, Washington

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

    Carpenter, M.R.; Easterbrook, D.J.

    1993-04-01

    Detailed investigation of an ancient sturzstrom or mega-landslide near Glacier, Washington has revealed it areal extent, approximate volume, age, geomorphology, source area, and possible causes. Stratigraphic and lithologic investigations indicate Church Mountain as the source area; therefore, this mega-landslide has been named the Church Mountain Sturzstrom (CMS). The CMS deposit is approximately 9 km in length, averages about 1 km in width, and has an estimated volume of 3 [times] 10[sup 8] m[sup 3]. Characteristics of the morphology and stratigraphy of the CMS deposit are suggestive of a sturzstrom origin, and may be indicative of sturzstrom elsewhere in the world.more » The overall stratigraphy of the deposit mimics the stratigraphy of the source area. The deposit is very compact, poorly sorted, matrix supported, and composed of highly angular clasts. Over steepening of the mountain due to glacial erosion may have contributed to the cause of failure, although the age of the CMS is at least 7,000 years younger than deglaciation. Four trees were C[sup 14] dated, yielding ages of about 2,700 B.P. for the CMS. Several other mega-landslides have been identified within 5--30 km of the CMS. The close proximity of these mega-landslides to the CMS suggests the possibility that they may have been triggered by an earthquake, although the ages of the other slides are currently unknown. The age of the CMS correlates approximately with age ranges of co-seismic events occurring along the west coast of Washington, further suggesting the possibility of an earthquake triggering mechanism.« less

  18. Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

    PubMed

    Cadby, Gemma; Melton, Phillip E; McCarthy, Nina S; Almeida, Marcio; Williams-Blangero, Sarah; Curran, Joanne E; VandeBerg, John L; Hui, Jennie; Beilby, John; Musk, A W; James, Alan L; Hung, Joseph; Blangero, John; Moses, Eric K

    2018-01-01

    Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

  19. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

    PubMed Central

    Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

    2017-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

  20. Combinatorial Polymer Matrices Enhance In Vitro Maturation of Human Induced Pluripotent Cell Cell-Derived Cardiomyocytes

    PubMed Central

    Chun, Young Wook; Balikov, Daniel A.; Feaster, Tromondae K.; Williams, Charles H.; Sheng, Calvin C.; Lee, Jung-Bok; Boire, Timothy C.; Neely, M. Diana; Bellan, Leon M.; Ess, Kevin C.; Bowman, Aaron B.; Sung, Hak-Joon; Hong, Charles C.

    2015-01-01

    Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-ε-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each % indicates the corresponding molar ratio) exhibit the greatest contractility and mitochondrial function. These functional enhancements are associated with increased expression of cardiac myosin light chain-2v, cardiac troponin I and integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-95%PCL demonstrate troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the postnatal cardiac TnI (cTnI), the first report of such transition in vitro. Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased expression of genes encoding intermediate filaments known to transduce integrin-mediated mechanical signals to the myofilaments. In summary, our study demonstrates that synthetic culture matrices engineered from combinatorial polymers can be utilized to promote in vitro maturation of human iPSC-CMs through the engagement of critical matrix-integrin interactions. PMID:26204225

  1. Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

    PubMed Central

    W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

    2013-01-01

    Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

  2. Stability of Colistin and Colistin Methanesulfonate in Aqueous Media and Plasma as Determined by High-Performance Liquid Chromatography

    PubMed Central

    Li, Jian; Milne, Robert W.; Nation, Roger L.; Turnidge, John D.; Coulthard, Kingsley

    2003-01-01

    The stabilities of colistin and colistin methanesulfonate (CMS) in different aqueous media were studied by specific high-performance liquid chromatography (HPLC) methods. Colistin was stable in water at 4 and 37°C for up to 60 days and 120 h, respectively. However, degradation was observed when colistin was stored in isotonic phosphate buffer (0.067 M, pH 7.4) and human plasma at 37°C. The stability of CMS from three different sources in water was explored by strong-anion-exchange (SAX) HPLC for CMS and by measuring the concentrations of colistin formed from the hydrolysis of CMS. The peaks of CMS in SAX HPLC disappeared almost completely after 12 h at 37°C, but appeared to remain intact for up to 2 days at 4°C. Over the same period, there was no formation of colistin at 4°C. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37°C from the three sources of CMS. The hydrolysis products were assumed to be a complex mixture of many different sulfomethyl derivatives, including colistin. The stability of a fourth source of CMS in Mueller-Hinton broth examined during 30 min at 37°C revealed no formation of colistin. Along with previous microbiological studies, this suggested that different sulfomethyl CMSs possess intrinsic antibacterial activity. These results will be helpful for understanding the pharmacokinetics and pharmacodynamics of colistin and CMS in humans and animals. PMID:12654671

  3. Impact of psychological screening on routine outpatient care of hematopoietic cell transplantation survivors.

    PubMed

    Hoodin, Flora; Zhao, Lili; Carey, Jillian; Levine, John E; Kitko, Carrie

    2013-10-01

    Hematopoietic cell transplantation recipients are at high risk for psychological distress, with reported prevalence rates as high as 40%. Although published guidelines advocate periodic routine screening, it is unclear how screening affects management of psychological symptoms at routine post-HCT outpatient clinic visits. We hypothesized that providers will be more likely to act on patients' psychological symptoms if a screening survey is completed and reviewed before a clinic visit. We used a brief, diagnostically focused Patient Health Questionnaire (PHQ), to assess for depressive disorders, anxiety, substance abuse, and problems in occupational or interpersonal functioning (functional disruption). Adult HCT survivors were randomized to complete the PHQ before meeting with their medical provider (n = 50; experimental group) or afterwards (n = 51; control group). Providers used the experimental group PHQ results at their discretion during the visits. Both providers and patients rated their satisfaction with management of psychological concerns after the visit. The prevalence of clinically significant depression (21%), anxiety (14%), or suicidal ideation (8%) did not differ between the 2 groups. Patients in the experimental group were significantly more likely to have discussion of psychological symptoms than the control group (68% versus 49%, P = .05). Medical providers were significantly more satisfied with the management of psychological issues for the experimental group (P < .001). Patients with depression or anxiety were significantly more likely to prefer the PHQ be used at future visits (P = .02 and P = .001, respectively). These findings suggest an informative yet brief self-report psychological screen can be easily integrated into routine care of hematopoietic cell transplantation survivors, stimulates discussion of psychological symptoms, and improves provider satisfaction with psychological symptom management. Future research will evaluate whether serial prospective administration improves patient outcomes. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Contamination of liquid oxygen by pressurized gaseous nitrogen

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J.; King, Tracy K.; Ngo, Kim Chi

    1989-01-01

    The penetration of pressurized gaseous nitrogen (GN2) into liquid oxygen (LOX) was investigated experimentally in the 7-inch High Temperature Tunnel, the pilot tunnel for the 8-foot High Temperature Tunnel (8'HTT) at Langley Research Center. A preliminary test using a nuclear monitor revealed the extent of the liquid nitrogen (LN2) build-up at the LOX interface as a function of GN2 pressure. Then an adaptation of the differential flash vaporization technique was used to determine the binary diffusivity of the LOX-LN2 system at a temperature of 90.2 K. The measured value D equals 0.000086 sq cm/s + or - 25 percent together with two prior measurements at lower temperatures revealed an excellent fit to the Arrhenius equation, yielding a pre-exponential factor D sub 0 equals 0.0452 sq cm/s and an activation enthalpy H equals 1.08 kcal/mol. At a pressure of 1700 psi and holding time of 15 min, the penetration of LN2 into LOX (to a 1 percent contamination level) was found to be 0.9 cm, indicating but minimal impact upon 8'HTT operations.

  5. J/ψ production and nuclear effects in p-Pb collisions at $$ \\sqrt{{{{\\mathrm{s}}_{\\mathrm{NN}}}}} $$ = 5.02 TeV

    DOE PAGES

    Abelev, B.; Adam, J.; Adamová, D.; ...

    2014-02-18

    We studied inclusive J/ψ production with the ALICE detector in p-Pb collisions at the nucleon-nucleon center of mass energy √s NN = 5.02 TeV at the CERN LHC. The measurement is performed in the center of mass rapidity domains 2.03 < y cms < 3.53 and -4.46 < y cms < -2.96, down to zero transverse momentum, studying the μ + μ - decay mode. In this paper, the J/ψ production cross section and the nuclear modification factor R pPb for the rapidities under study are presented. Moreover, while at forward rapidity, corresponding to the proton direction, amore » suppression of the J/ψ yield with respect to binary-scaled pp collisions is observed, in the backward region no suppression is present. Finally, the ratio of the forward and backward yields is also measured differentially in rapidity and transverse momentum. Theoretical predictions based on nuclear shadowing, as well as on models including, in addition, a contribution from partonic energy loss, are in fair agreement with the experimental results.« less

  6. Experimental parametric study of a biomimetic fish robot actuated by piezoelectric actuators

    NASA Astrophysics Data System (ADS)

    Wiguna, T.; Park, Hoon C.; Heo, S.; Goo, Nam S.

    2007-04-01

    This paper presents an experiment and parametric study of a biomimetic fish robot actuated by the Lightweight Piezocomposite Actuator (LIPCA). The biomimetic aspects in this work are the oscillating tail beat motion and shape of caudal fin. Caudal fins that resemble fins of BCF (Body and Caudal Fin) mode fish were made in order to perform parametric study concerning the effect of caudal fin characteristics on thrust production at an operating frequency range. The observed caudal fin characteristics are the shape, stiffness, area, and aspect ratio. It is found that a high aspect ratio caudal fin contributes to high swimming speed. The robotic fish propelled by artificial caudal fins shaped after thunniform-fish and mackerel caudal fins, which have relatively high aspect ratio, produced swimming speed as high as 2.364 cm/s and 2.519 cm/s, respectively, for a 300 V p-p input voltage excited at 0.9 Hz. Thrust performance of the biomimetic fish robot is examined by calculating Strouhal number, Froude number, Reynolds number, and power consumption.

  7. Viscous Flow Causes Weakening in Calcite Nanogouges Sheared at Seismic Velocity

    NASA Astrophysics Data System (ADS)

    Pozzi, G.; De Paola, N.; Nielsen, S. B.; Holdsworth, R.

    2016-12-01

    Recent experimental studies have suggested that the activation of diffusion creep at high temperatures (T ≥ 800 °C) and strain rates in nanograin aggregates can weaken faults and facilitate earthquake propagation. However, the frictional properties of nanoscale aggregates at high strain rates and T are still poorly investigated and, in particular, their flow laws at these extreme conditions are poorly constrained due to lack of knowledge about the evolution of grain size and strain localization during seismic slip. Experiments performed in a rotary shear apparatus on micro- and nano-metric calcite gouges (d=63-90 µm and d 200nm, respectively) at seismic (up to 1.4 m/s) and subseismic (<10 cm/s) velocities, arrested at different amounts of slip, show that: (i) onset of dynamic weakening in the nanogouge is faster, with a significantly reduced initial phase of slip hardening, (ii) dynamic weakening of the nanogouge is achieved at velocities and temperatures as low as 1.4 cm/s and <300°C, respectively, compared to >10 cm/s and >500°C in the microgouge, (iii) shear strength shows a rate-dependent weakening. Microstructural analysis of samples shows a three stage evolution: (i) cataclastic comminution and development of Riedel shear bands during the pre-weakening slip-hardening stage, (ii) interconnection of Riedel shears to form a continuous horizontal, localised shear band at the onset of weakening and (iii) evolution of the latter into a thin discrete shear zone with thickness <200 µm composed by a low-porosity aggregate of equigranular recrystallized crystals displaying triple junctions, at the attainment of steady-state weakening stage. Microstructures up to stage (i) are achieved in samples that did not undergo weakening. Despite both gouges show the same microstructural evolution, the initial grainsize of nanoparticles allows a more efficient localisation as the development of a discrete slip zone requires smaller amounts of slip. Our experimental results and microstructural observations shed some light on the critical role that extreme comminution and localisation play on the onset of weakening dominated by viscous flow at high strain rate in carbonate gouges.

  8. 42 CFR 457.150 - CMS review of State plan material.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... State plan material. (a) Basis for action. CMS reviews each State plan and plan amendment to determine... on complete plan. CMS approves or disapproves the State plan or plan amendment only in its entirety... disapprove the State plan or plan amendment, or to determine that previously approved material no longer...

  9. Status and commissioning of the CMS experiment

    NASA Astrophysics Data System (ADS)

    Wulz, C.-E.

    2008-05-01

    The construction status of the CMS experiment at the Large Hadron Collider and strategies for commissioning the subdetectors, the magnet, the trigger and the data acquisition are described. The first operations of CMS as a unified system, using either cosmic rays or test data, and the planned activities until the startup of the LHC are presented.

  10. 42 CFR 457.150 - CMS review of State plan material.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction; State Plans for Child Health Insurance Programs and Outreach Strategies § 457.150 CMS review of... 42 Public Health 4 2010-10-01 2010-10-01 false CMS review of State plan material. 457.150 Section...

  11. 76 FR 24034 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ... discussed at workgroup meetings. In turn, CMS' HCPCS workgroup reaches a decision as to whether a change... Level II Codes. As a result, the National Panel was delineated and CMS continued with the decision-making process under its current structure, the CMS HCPCS Workgroup (herein referred to as ``the...

  12. 78 FR 41931 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ...). CMS-2746 End Stage Renal Disease Death Notification CMS-2728 End Stage Renal Disease Medical Evidence...: End Stage Renal Disease Death Notification; Use: The End Stage Renal Disease (ESRD) Death Notification (CMS-2746) is completed by all Medicare-approved ESRD facilities upon the death of an ESRD patient. Its...

  13. 42 CFR 422.308 - Adjustments to capitation rates, benchmarks, bids, and payments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... equivalence. CMS may add to, modify, or substitute for risk adjustment factors if those changes will improve... adjust for health status, CMS applies a risk factor based on data obtained in accordance with § 422.310. (ii) Implementation. CMS applies a risk factor that incorporates inpatient hospital and ambulatory...

  14. 76 FR 55917 - Medicare Program; Notification of Closure of St. Vincent's Medical Center; Extension of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-1587-N2... Submission of Applications AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice of... hospitals to apply to the Centers for Medicare & Medicaid Services (CMS) to receive St. Vincent's Medical...

  15. Interspecific amphiploid-derived alloplasmic male sterility with defective anthers, narrow disk florets, and small ray flowers in sunflower

    USDA-ARS?s Scientific Manuscript database

    The cytoplasmic male-sterility (CMS)/fertility-restoration system is important for hybrid sunflower (Helianthus annuus L.) seed production. Two novel alloplasmic CMSs, designated CMS GRO1 and CMS MAX3 with defective anthers, narrow disk florets with no swollen corolla, and short, narrow ray flowers,...

  16. 77 FR 59616 - Medicare and Medicaid Programs; Approval of the American Osteopathic Association/Healthcare...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-3264-FN... Accreditation Program (AOA/HFAP) Application for Continuing CMS-Approval of Its Ambulatory Surgical Center (ASC... 6 years or sooner as determined by CMS. AOA/HFAP's current term of approval for their ASC...

  17. 78 FR 57857 - Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ...] Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of its Rural... Compliance Team for initial recognition as a national accrediting organization for rural health clinics (RHCs... Compliance Team's request for initial CMS approval of its RHC accreditation program. This notice also...

  18. Training ELF Teachers to Create a Blended Learning Environment: Encouraging CMS Adoption and Implementation

    ERIC Educational Resources Information Center

    Cote, Travis; Milliner, Brett

    2015-01-01

    E-learning has become a crucial component of most tertiary institution's education initiatives (Park, Lee, & Cheong, 2007) and core to most e-learning strategies is the institution's Content Management System (CMS). A CMS has the potential to enhance language courses by facilitating engagement with class content, providing students with…

  19. Health economics perspective of the components of the cardiometabolic syndrome.

    PubMed

    Tamariz, Leonardo; Palacio, Ana; Yang, Yadong; Parris, Donald; Ben-Joseph, Rami; Florez, Hermes

    2010-07-01

    The components of the cardiometabolic syndrome (CMS) increase the risk of coronary artery disease (CAD). The authors compared 12-month costs of subjects with different number of components of the CMS. In claims data from a large health benefits company, 383,420 individuals with the first International Classification of Diseases, Ninth Revision codes for hypertension, diabetes, lipid abnormalities, and obesity were identified. Patients were stratified according to presence of CAD and the number of components of the CMS. Twelve-month costs were added after the identification of the risk factor. Mean annual costs increased with the number of components of CMS both in those with and without CAD, even after adjusting for age, sex, and comorbidities (P<.01). Similar trends were seen for medical and pharmacy costs. The adjusted total annual health care cost in those with an isolated component of the CMS was $5564 (95% confidence interval: $5491-$5631) while in those with 4 components was $12,287 (95% confidence interval: $11,987-$12,587). Individuals with accumulating components of the CMS have higher health care costs regardless of age, sex, and other comorbidities.

  20. Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives.

    PubMed

    Chow, Maggie; Boheler, Kenneth R; Li, Ronald A

    2013-08-14

    Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications.

  1. Challenging data and workload management in CMS Computing with network-aware systems

    NASA Astrophysics Data System (ADS)

    D, Bonacorsi; T, Wildish

    2014-06-01

    After a successful first run at the LHC, and during the Long Shutdown (LS1) of the accelerator, the workload and data management sectors of the CMS Computing Model are entering into an operational review phase in order to concretely assess area of possible improvements and paths to exploit new promising technology trends. In particular, since the preparation activities for the LHC start, the Networks have constantly been of paramount importance for the execution of CMS workflows, exceeding the original expectations - as from the MONARC model - in terms of performance, stability and reliability. The low-latency transfers of PetaBytes of CMS data among dozens of WLCG Tiers worldwide using the PhEDEx dataset replication system is an example of the importance of reliable Networks. Another example is the exploitation of WAN data access over data federations in CMS. A new emerging area of work is the exploitation of Intelligent Network Services, including also bandwidth on demand concepts. In this paper, we will review the work done in CMS on this, and the next steps.

  2. CMS issues updated rules for the Medicare claims appeal process.

    PubMed

    Davidson, Nancy J

    2003-01-01

    BIPA requires extensive changes to Medicare's appeal process. However, due to the lack of funding and adequate resources, CMS has been unable to immediately implement many of BIPA's far-reaching changes. CMS is committed to making a transition to the new process as quickly as possible and intends to implement as many key issues as feasible within budget and resource limits. Once Congress allocates funds for the new changes, CMS will be in a better position to implement all aspects of BIPA. [table: see text] The most significant change that BIPA presents is that Congress will require 12 new contractors to handle Part A and Part B appeals. These entities will be known as qualified independent contractors (QICs). CMS has completed development of the requests for proposals needed to solicit bids for the QIC contracts, including full statements of the scope of work (SOW) for these contracts. CMS released the draft SOW on Oct. 7, 2002. It is anticipated that the addition of the QICs will provide a more uniform and consistent handling of Medicare appeals on a national level.

  3. Self-assembly behaviour of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization

    PubMed Central

    Wallace, Stephanie J.; Li, Jian; Nation, Roger L.; Prankerd, Richard J.; Velkov, Tony; Boyd, Ben J.

    2010-01-01

    Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS) was investigated. Colistin and CMS reduced the air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 ± 0.3 nm aggregates above 1.5 mM for colistin, and of 1.98 ± 0.36 nm aggregates for CMS above 3.5 mM (mean ± SD). Above the respective critical micelle concentrations (CMC) the solubility of azithromycin, a hydrophobic antibiotic, increased approximately linearly with increasing surfactant concentration (5:1 mol ratio colistin:azithromycin), suggestive of hydrophobic domains within the micellar cores. Rapid conversion of CMS to colistin occurred below the CMC (60 % over 48 hr), while conversion above the CMC was less than 1 %. The formation of colistin and CMS micelles demonstrated in this study is the proposed mechanism for solubilization of azithromycin and the concentration-dependent stability of CMS. PMID:20302384

  4. The Archive Solution for Distributed Workflow Management Agents of the CMS Experiment at LHC

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

    Kuznetsov, Valentin; Fischer, Nils Leif; Guo, Yuyi

    The CMS experiment at the CERN LHC developed the Workflow Management Archive system to persistently store unstructured framework job report documents produced by distributed workflow management agents. In this paper we present its architecture, implementation, deployment, and integration with the CMS and CERN computing infrastructures, such as central HDFS and Hadoop Spark cluster. The system leverages modern technologies such as a document oriented database and the Hadoop eco-system to provide the necessary flexibility to reliably process, store, and aggregatemore » $$\\mathcal{O}$$(1M) documents on a daily basis. We describe the data transformation, the short and long term storage layers, the query language, along with the aggregation pipeline developed to visualize various performance metrics to assist CMS data operators in assessing the performance of the CMS computing system.« less

  5. The Archive Solution for Distributed Workflow Management Agents of the CMS Experiment at LHC

    DOE PAGES

    Kuznetsov, Valentin; Fischer, Nils Leif; Guo, Yuyi

    2018-03-19

    The CMS experiment at the CERN LHC developed the Workflow Management Archive system to persistently store unstructured framework job report documents produced by distributed workflow management agents. In this paper we present its architecture, implementation, deployment, and integration with the CMS and CERN computing infrastructures, such as central HDFS and Hadoop Spark cluster. The system leverages modern technologies such as a document oriented database and the Hadoop eco-system to provide the necessary flexibility to reliably process, store, and aggregatemore » $$\\mathcal{O}$$(1M) documents on a daily basis. We describe the data transformation, the short and long term storage layers, the query language, along with the aggregation pipeline developed to visualize various performance metrics to assist CMS data operators in assessing the performance of the CMS computing system.« less

  6. Carboxymethyl starch/montmorillonite composite microparticles: Properties and controlled release of isoproturon.

    PubMed

    Wilpiszewska, Katarzyna; Spychaj, Tadeusz; Paździoch, Waldemar

    2016-01-20

    Preparation of novel high substituted carboxymethyl starch-based microparticles containing sodium montmorillonite (MMT) by crosslinking with Al(3+) was described. For preparing nanocomposite granules carboxymethyl starch (CMS) from native potato starch as well as CMS from amylopectin has been used. The hydrophilic CMS/MMT composite systems were used for herbicide, i.e. isoproturon encapsulation (ca. 75% encapsulation efficiency). The herbicide release rate from CMS/MMT composites in water was significantly reduced when compared to commercial isoproturon: 95% released after ca. 700 h and ca. 24h, respectively. Leaching in soil from composite systems was relatively slower than release in water. After a series of eight irrigations leached about 10% of isoproturon loaded. The CMS/MMT carriers could reduce the potential leaching of herbicide and beneficially reduce pollution of the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. First study of the sensitivity of CMS detector to neutrinoless decay chanNel t?µ+µ+µ-

    NASA Astrophysics Data System (ADS)

    Santinelli, Roberto

    2002-01-01

    After the recent results coming from Super Kamiokande experiments, the problem of the lepton flavor violation is one of the most important channel of front end investigation. We made a preliminary study of the possibility to observe at CMS the Standard Model forbidden decay ‰̅w. The improvement of experimental sensitivity of the Branching Ratio would be of interest either in a discovery search, or in a study of the exclusion limit bringing information on the SUSY scenario potentially at work. We will focus now on one of the most promising source of tau lepton at LHC for our signal, the W's boson going in a tau lepton plus neutrino thus leading to three muons plus ETmiss as final state signature. The most challenging aspect on this type of analysis is to understand and then to isolate the background. A detailed study of the whole set of possible sources of muons at LHC, leads to consider the heavy quarks mesons decays with three muons in the final state from a single meson as the principal and the most dangerous source of background events. A fast simulation of the CMS detector based analysis shows that the background could be completely suppressed leading to an exclusion limit 50 times lower than the one set by CLEO II. The analysis has been limited for the time being to the barrel region m<0.9.

  8. A model of determining a fair market value for teaching residents: who profits?

    PubMed

    Cullen, Edward J; Lawless, Stephen T; Hertzog, James H; Penfil, Scott; Bradford, Kathleen K; Nadkarni, Vinay M; Corddry, David H; Costarino, Andrew T

    2003-07-01

    Centers for Medicare & Medicaid Services (CMS) Health Resources and Services Administration Children's Hospitals Graduate Medical Education (GME) Payment Program now supports freestanding children's teaching hospitals. To analyze the fair market value impact of GME payment on resident teaching efforts in our pediatric intensive care unit (PICU). Cost-accounting model, developed from a 1-year retrospective, descriptive, single-institution, longitudinal study, applied to physician teachers, residents, and CMS. Sixteen-bed PICU in a freestanding, university-affiliated children's teaching hospital. Pediatric critical care physicians, second-year residents. Cost of physician opportunity time; CMS investment return; the teaching physicians' investment return; residents' investment return; service balance between CMS and teaching service investment margins; economic balance points; fair market value. GME payments to our hospital increased 4.8-fold from 577 886 dollars to 2 772 606 dollars during a 1-year period. Critical care physicians' teaching opportunity cost rose from 250 097 dollars to 262 215 dollars to provide 1523 educational hours (6853 relative value units). Residents' net financial value for service provided to the PICU rose from 245 964 dollars to 317 299 dollars. There is an uneven return on investment in resident education for CMS, critical care physicians, and residents. Economic balance points are achievable for the present educational efforts of the CMS, critical care physicians, and residents if the present direct medical education payment increases from 29.38% to 36%. The current CMS Health Resources and Services Administration Children's Hospitals GME Payment Program produces uneven investment returns for CMS, critical care physicians, and residents. We propose a cost-accounting model, based on perceived production capability measured in relative value units and available GME funds, that would allow a clinical service to balance and obtain a fair market value for the resident education efforts of CMS, physician teachers, and residents.

  9. Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness.

    PubMed

    Villafuerte, Francisco C; Corante, Noemí; Anza-Ramírez, Cecilia; Figueroa-Mujíca, Rómulo; Vizcardo-Galindo, Gustavo; Mercado, Andy; Macarlupú, José Luis; León-Velarde, Fabiola

    2016-07-01

    Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia. Copyright © 2016 the American Physiological Society.

  10. Intelligent systems and advanced user interfaces for design, operation, and maintenance of command management systems

    NASA Technical Reports Server (NTRS)

    Potter, William J.; Mitchell, Christine M.

    1993-01-01

    Historically, command management systems (CMS) have been large and expensive spacecraft-specific software systems that were costly to build, operate, and maintain. Current and emerging hardware, software, and user interface technologies may offer an opportunity to facilitate the initial formulation and design of a spacecraft-specific CMS as well as to develop a more generic CMS system. New technologies, in addition to a core CMS common to a range of spacecraft, may facilitate the training and enhance the efficiency of CMS operations. Current mission operations center (MOC) hardware and software include Unix workstations, the C/C++ programming languages, and an X window interface. This configuration provides the power and flexibility to support sophisticated and intelligent user interfaces that exploit state-of-the-art technologies in human-machine interaction, artificial intelligence, and software engineering. One of the goals of this research is to explore the extent to which technologies developed in the research laboratory can be productively applied in a complex system such as spacecraft command management. Initial examination of some of these issues in CMS design and operation suggests that application of technologies such as intelligent planning, case-based reasoning, human-machine systems design and analysis tools (e.g., operator and designer models), and human-computer interaction tools (e.g., graphics, visualization, and animation) may provide significant savings in the design, operation, and maintenance of the CMS for a specific spacecraft as well as continuity for CMS design and development across spacecraft. The first six months of this research saw a broad investigation by Georgia Tech researchers into the function, design, and operation of current and planned command management systems at Goddard Space Flight Center. As the first step, the researchers attempted to understand the current and anticipated horizons of command management systems at Goddard. Preliminary results are given on CMS commonalities and causes of low re-use, and methods are proposed to facilitate increased re-use.

  11. The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

    PubMed

    Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

    Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

  12. Chinese version of the Constant-Murley questionnaire for shoulder pain and disability: a reliability and validation study.

    PubMed

    Yao, Min; Yang, Long; Cao, Zuo-Yuan; Cheng, Shao-Dan; Tian, Shuang-Lin; Sun, Yue-Li; Wang, Jing; Xu, Bao-Ping; Hu, Xiao-Chun; Wang, Yong-Jun; Zhang, Ying; Cui, Xue-Jun

    2017-09-18

    Shoulder pain is a common musculoskeletal disorder in Chinese population, which affects more than 1,3 billion individuals. To the best of our knowledge, there has been no available Chinese-language version of measurements of shoulder pain and disability so far. Moreover, the Constant-Murley score (CMS) questionnaire is a universally recognized patient-reported questionnaire for clinical practice and research. The present study was designed to evaluate a Chinese translational version of CMS and subsequently assess its reliability and validity. The Chinese translational version of CMS was formulated by means of forward-backward translation. Meanwhile, a final review was carried out by an expert committee, followed by conducting a test of the pre-final version. Therefore, the reliability and validity of the Chinese translational version of CMS could be assessed using the internal consistency, construct validity, factor analysis, reliability and floor and ceiling effects. Specifically, the reliability was assessed by testing the internal consistency (Cronbach's α) and test-retest reliability (intraclass coefficient correlation [ICC]), while the construct validity was evaluated via comparison between the Chinese translational version of CMS with visual analog scale (VAS) score and the 36-Item Short Form Health Survey (SF-36, Spearman correlation). The questionnaire was verified to be acceptable after distribution among 120 subjects with unilateral shoulder pain. Factor analysis had revealed a two-factor and 10-item solution. Moreover, the assessment results indicated that the Chinese translational version of CMS questionnaire harbored good internal consistency (Cronbach's α = 0.739) and test-retest reliability (ICC = 0.827). In addition, the Chinese translational version of CMS was moderately correlated with VAS score (r = 0.497) and SF-36 (r = 0.135). No obvious floor and ceiling effects were observed in the Chinese translational version of CMS questionnaire. Chinese translational version of CMS exhibited good reliability, which is relatively acceptable and is likely to be widely used in this population.

  13. Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

    PubMed Central

    Corante, Noemí; Anza-Ramírez, Cecilia; Figueroa-Mujíca, Rómulo; Vizcardo-Galindo, Gustavo; Mercado, Andy; Macarlupú, José Luis; León-Velarde, Fabiola

    2016-01-01

    Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia. PMID:27125843

  14. Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

    PubMed

    Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

    2017-01-01

    Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression-alcoholism relationship still deserves further investigation. Copyright © 2016. Published by Elsevier Inc.

  15. Development of BEM for ceramic composites

    NASA Technical Reports Server (NTRS)

    Henry, D. P.; Banerjee, P. K.; Dargush, G. F.; Hopkins, D. A.; Goldberg, R. K.

    1993-01-01

    BEST-CMS (boundary element solution technology - composite modeling system) is an advanced engineering system for the micro-analysis of fiber composite structures. BEST-CMS is based upon the boundary element program BEST3D which was developed for NASA by Pratt and Whitney Aircraft and the State University of New York at Buffalo under contract NAS3-23697. BEST-CMS presently has the capabilities for elastostatic analysis, steady-state and transient heat transfer analysis, steady-state and transient concurrent thermoelastic analysis, and elastoplastic and creep analysis. The fibers are assumed to be perfectly bonded to the composite matrix, or in the case of static or steady-state analysis, the fibers may be assumed to have spring connections, thermal resistance, and/or frictional sliding between the fibers and the composite matrix. The primary objective of this user's manual is to provide an overview of all BEST-CMS capabilities, along with detailed descriptions of the input data requirements. In the next chapter, a brief review of the theoretical background is presented for each analysis category. Then, chapter three discusses the key aspects of the numerical implementation, while chapter four provides a tutorial for the beginning BEST-CMS user. The heart of the manual, however, is in chapter five, where a complete description of all data input items is provided. Within this chapter, the individual entries are grouped on a functional basis for a more coherent presentation. Chapter six includes sample problems and should be of considerable assistance to the novice. Chapter seven includes capsules of a number of fiber-composite analysis problems that have been solved using BEST-CMS. This chapter is primarily descriptive in nature and is intended merely to illustrate the level of analysis that is possible within the present BEST-CMS system. Chapter eight contains a detail description of the BEST-CMS Neutral File which is helpful in writing an interface between BEST-CMS and any graphic post-processor program. Finally, all pertinent references are listed in chapter nine.

  16. Home Visiting for At-Risk Preschoolers: A Successful Model for Latino Families

    ERIC Educational Resources Information Center

    Nievar, M. Angela; Jacobson, A.; Dier, S.

    2008-01-01

    The Home Instruction for Parents of Preschool Youngsters (HIPPY) program promotes school readiness by providing services directly to parents through home visitation. This study describes the outcomes of the HIPPY program for Latino immigrant families in a large Southwestern city. A quasi-experimental design compared 48 families on the program…

  17. The effect of visiting surgical patients in the postanesthesia care unit on family members' anxiety: a prospective quasi-experimental study.

    PubMed

    Patelarou, Athina; Melidoniotis, Evangelos; Sgouraki, Maria; Karatzi, Maria; Souvatzis, Xenia

    2014-06-01

    Surgical procedures pose stressful events for patients and their family members. The main purpose of this study was to determine if visiting patients in the postanesthesia care unit (PACU) would reduce the anxiety levels of Greek patients' family members. A prospective study with a one-group quasi-experimental pretest/post-test design was used. Situational anxiety of surgical patients' relatives was assessed using the state subscale of the State-Trait Anxiety Inventory (STAI; Greek validation) at the beginning of the surgical procedure and again after their visitation of patients in the PACU. STAI scores were significantly higher preoperatively (57 [23-80]) than postoperatively (51 [21-77]; P=.000008). Clinically significant levels of anxiety were present in 76% and 58% of the participants, pre- and postoperatively, respectively. Although postoperative STAI scores were reduced, family visitation in the PACU did not sufficiently reduce the anxiety of Greek family members to clinically acceptable levels. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  18. Rheology of welding: experimental constraints

    NASA Astrophysics Data System (ADS)

    Quane, S. L.; Russell, J. K.; Kennedy, L. A.

    2003-04-01

    The rheological behavior of pyroclastic deposits during welding is incompletely understood and is based on a surprisingly small number of experimental studies. Previous pioneering experimental studies were done on small (1 cm thick) samples of ash/crystal mixtures under constant load. They established minimum welding temperatures between 600 and 700^oC under loads of 0.7 MPa (˜40 m of ignimbrite) to 3.6 MPa (˜250 m depth of ignimbrite). However, these data are neither sufficiently comprehensive nor coherent enough to fully describe the rheology of pyroclastic mixtures. In addition, previous studies did not examine the microstructural and geometric changes associated with welding compaction. Our goal is to provide accurate and comprehensive constitutive relationships between material properties, temperature, load and strain rate for pyroclastic material undergoing welding. Here we present results from a newly designed experimental apparatus. The experimental apparatus consists of a LoadTrac II fully automated uniaxial compression load frame manufactured by Geocomp Corporation. The load frame has a built in displacement transducer and can run both constant strain rate (10-6 to 0.25 cm/s) and constant load (up to 1150 kg) tests to a maximum displacement of 7.5 cm. The sample assembly comprises 5 cm diameter cylindrical upper and lower pistons (insulating ceramic with steel conductive ends) housed in a copper jacket. Samples are 5 cm diameter cores and can vary in length from 1 to 15 cm depending on experimental needs. A fiber insulated tube furnace capable of reaching temperatures ≈1000^oC surrounds the sample assembly. Temperature is measured using a thermocouple located inside the sample through the bottom piston; the furnace controller is capable of maintaining temperature fluctuations to <5^oC. Deformation experiments are performed on pre-fabricated cylinders of soda-lime glass beads and rhyolitic volcanic ash, as well as, cores of pumiceous rhyodacite. Experimental runs use strain rates of 10-4 and 10-5 cm/s and loads of ˜0 to 4.5 MPa. Experiments are run at temperatures between 400 and 850^oC corresponding to below and above the calorimetric glass transition temperatures of the respective materials. Data deriving from constant load and constant strain rate experiments are being used to constrain rheological models for welding of pyroclastic material.

  19. The profitability of automatic milking on Dutch dairy farms.

    PubMed

    Bijl, R; Kooistra, S R; Hogeveen, H

    2007-01-01

    Several studies have reported on the profitability of automatic milking based on different simulation models, but a data-based study using actual farm data has been lacking. The objective of this study was to analyze the profitability of dairy farms having an automatic milking system (AMS) compared with farms using a conventional milking system (CMS) based on real accounting data. In total, 62 farms (31 using an AMS and 31 using a CMS) were analyzed for the year 2003 in a case control study. Differences between the years 2002 and 2003 also were analyzed by comparing a subgroup of 16 farms with an AMS and 16 farms with a CMS. Matching was based on the time of investment in a milking system (same year), the total milk production per year, and intensity of land use (kg/ha). Results from 2003 showed that the farms with an AMS used, on average, 29% less labor than farms with a CMS. In contrast, farms using a CMS grew faster (37,132 kg of milk quota and 5 dairy cows) than farms with an AMS (-3,756 kg milk quota and 0.5 dairy cows) between 2002 and 2003. Dairy farmers with a CMS had larger (euro7,899) revenues than those with an AMS. However, no difference in the margin on dairy production was detected, partly because of numerically greater (euro6,822) variable costs on CMS farms. Dairy farms were compared financially based on the amount of money that was available for rent, depreciation, interest, labor, and profit (RDILP). The CMS farms had more money (euro15,566) available for RDILP than the AMS farms. This difference was caused by larger fixed costs (excluding labor) for the AMS farms, larger contractor costs (euro6,422), and larger costs for gas, water, and electricity (euro1,549). Differences in costs for contractors and for gas, water, and electricity were statistically significant. When expressed per full-time employee, AMS farms had greater revenues, margins, and gross margins per full-time employee than did CMS farms. This resulted in a substantially greater (but not statistically significant) RDILP per full-time employee (euro12,953) for AMS farms compared with CMS farms. Depreciation and interest costs for automatic milking were not available but were calculated based on several assumptions. Assuming larger purchase costs and a shorter depreciation time for AMS than for CMS, costs for depreciation and interest were larger for AMS farms than for CMS farms. Larger fixed costs should be compensated for by the amount of labor that has become available after introducing the milking robot. Therefore, farm managers should decide whether the extra time acquired by automatic milking balances against the extra costs associated with an AMS.

  20. Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery.

    PubMed

    Zhao, Qinfu; Geng, Hongjian; Wang, Ying; Gao, Yikun; Huang, Jiahao; Wang, Yan; Zhang, Jinghai; Wang, Siling

    2014-11-26

    A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.

  1. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

    PubMed

    Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

    2015-05-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

  2. The Brazilian version of the Constant-Murley Score (CMS-BR): convergent and construct validity, internal consistency, and unidimensionality.

    PubMed

    Barreto, Rodrigo Py Gonçalves; Barbosa, Marcus Levi Lopes; Balbinotti, Marcos Alencar Abaide; Mothes, Fernando Carlos; da Rosa, Luís Henrique Telles; Silva, Marcelo Faria

    2016-01-01

    To translate and culturally adapt the CMS and assess the validity of the Brazilian version (CMS-BR). The translation was carried out according to the back-translation method by four independent translators. The produced versions were synthesized through extensive analysis and by consensus of an expert committee, reaching a final version used for the cultural adaptation. A field test was conducted with 30 subjects in order to obtain semantic considerations. For the psychometric analyzes, the sample was increased to 110 participants who answered two instruments: CMS-BR and the Disabilities of the Arm, shoulder and Hand (DASH). The CMS-BR and DASH score range from 0 to 100 points. For the first, higher points reflect better function and for the latter, the inverse is true. The validity was verified by Pearson's correlation test, the unidimensionality by factorial analysis, and the internal consistency by Cronbach's alpha. The explained variance was 60.28% with factor loadings ranging from 0.60 to 0.91. The CMS-BR exhibited strong negative correlation with the DASH score (-0.82, p  < 0.05), Cronbach's alpha 0.85, and its total score was strongly correlated with the patient's range of motion (0.93, p  < 0.001). The CMS was satisfactorily adapted for Brazilian Portuguese and demonstrated evidence of validity that allows its use in this population.

  3. Draft genome of Kocuria polaris CMS 76or(T) isolated from cyanobacterial mats, McMurdo Dry Valley, Antarctica: an insight into CspA family of proteins from Kocuria polaris CMS 76or(T).

    PubMed

    Gundlapally, Sathyanarayana Reddy; Ara, Srinivas; Sisinthy, Shivaji

    2015-10-01

    Kocuria polaris strain CMS 76or(T) is a gram-positive, orange-pigmented bacterium isolated from a cyanobacterial mat sample from a pond located in McMurdo Dry Valley, Antarctica. It is psychrotolerant, orange pigmented, hydrolyses starch and Tween 80 and reduces nitrate. We report the 3.78-Mb genome of K. polaris strain CMS 76or(T), containing 3416 coding sequences, including one each for 5S rRNA, 23S rRNA, 16S rRNA and 47 tRNA genes, and the G+C content of DNA is 72.8%. An investigation of Csp family of proteins from K. polaris strain CMS 76or(T) indicated that it contains three different proteins of CspA (peg.319, peg.2255 and 2832) and the length varied from 67 to 69 amino acids. The three different proteins contain all the signature amino acids and two RNA binding regions that are characteristic of CspA proteins. Further, the CspA from K. polaris strain CMS 76or(T) was different from CspA of four other species of the genus Kocuria, Cryobacterium roopkundense and E. coli indirectly suggesting the role of CspA of K. polaris strain CMS 76or(T) in psychrotolerant growth of the bacterium.

  4. 42 CFR 488.68 - State Agency responsibilities for OASIS collection and data base requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... operating the OASIS system: (a) Establish and maintain an OASIS database. The State agency or other entity designated by CMS must— (1) Use a standard system developed or approved by CMS to collect, store, and analyze..., system back-up, and monitoring the status of the database; and (3) Obtain CMS approval before modifying...

  5. 42 CFR 495.204 - Incentive payments to qualifying MA organizations for MA-EPs and MA-affiliated eligible hospitals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... (iii) Methodological proposals must be submitted to CMS by June of the payment year and must be... the payment year. (4) CMS requires the qualifying MA organization to develop a methodological proposal... MA organization in the payment year. The methodological proposal— (i) Must be approved by CMS; and...

  6. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  7. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  8. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  9. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  10. 45 CFR 150.317 - Factors CMS uses to determine the amount of penalty.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... level of financial and other impacts on affected individuals. (3) Other factors as justice may require. ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Factors CMS uses to determine the amount of... With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.317 Factors CMS...

  11. 77 FR 3477 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... collection for the proper performance of the agency's functions; (2) the accuracy of the estimated burden; (3... submitted to CMS through the 372 web-based form. The report is used by CMS to compare actual data in the... provided is compared to that in the Medicaid Statistical Information System (CMS-R-284, OCN 0938-0345...

  12. Better Off with or without Your CMS? 5 Kinds of Assessment That Can Really Help.

    ERIC Educational Resources Information Center

    Ehrmann, Stephen C.; Gilbert, Steven W.

    2003-01-01

    Presents five areas to consider to help establish the value and improve the effectiveness of a course management system (CMS). Highlights include faculty use to improve teaching effectiveness; changes in support strategies to improve the value of a CMS; increasing enrollment or retention; controlling costs; and identifying barriers to desired…

  13. 75 FR 80058 - Notice of Hearing: Reconsideration of Disapproval of California State Plan Amendments (SPAs) 08...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ...; and 08-019 AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice of hearing. SUMMARY: This notice announces an administrative hearing to be held on February 10, 2011, at the CMS San Francisco Regional Office, 90 7th Street, 5-300 (5W), San Francisco, California 94103 to reconsider CMS...

  14. Coastal Modeling System

    DTIC Science & Technology

    2015-11-04

    Coastal Inlets Research Program Coastal Modeling System The work unit develops the Coastal Modeling System ( CMS ) and conducts basic research to...further understanding of sediment transport under mixed oceanic and atmospheric forcing. The CMS is a suite of coupled two-dimensional numerical...models for simulations of waves, hydrodynamics, salinity and sediment transport, and morphology change. The CMS was identified by the USACE Hydraulics

  15. Tool-Use in a Content Management System: A Matter of Timing?

    ERIC Educational Resources Information Center

    Lust, Griet; Vandewaetere, Mieke; Elen, Jan; Clarebout, Geraldine

    2014-01-01

    Given the rising popularity of content management systems (CMSs) in higher education, we investigated how students use the available CMS tools, as well as whether the moment of using a CMS tool affects students' learning. This temporal dimension has been neglected in current research on CMS use. More insight into students' tool-use is…

  16. A Planning and Assessment Model for Developing Effective CMS Support

    ERIC Educational Resources Information Center

    Johnson, Douglas F.

    2004-01-01

    At the University of Florida, in Spring 2003, more than 32,000 individuals enrolled in courses using the centrally-supported Course Management System (CMS). Because less than 1 full time equivalent (FTE) was allocated to support the CMS, this created problems for both users and support providers. In the face of rapid growth, support resources for…

  17. Propagation of a premixed flame in a divided-chamber combustor

    NASA Technical Reports Server (NTRS)

    Cattolica, R. J.; Barr, P. K.; Mansour, N. N.

    1989-01-01

    Experimental observations on the propagation of lean premixed ethylene-air flames in a divided-chamber combustion vessel have been compared with the results of numerical simulations based on a flame sheet-vortex dynamics model in axisymmetric coordinates. Flame speeds were found to increase from 10-24 cm/s as the equivalence ratio was varied from 0.5-0.65 in the experiments. Using the associated increase in gas velocity with equivalence ratio, the estimated Reynolds number in the experiment was changed from 1870 to 8090. Good agreement between experimental and theoretical results was obtained for the prechamber flame propagation rates and for the spatial and temporal development of the flame in the main combustion chamber at the lowest Reynolds number.

  18. Usage of machine learning for the separation of electroweak and strong Zγ production at the LHC experiments

    NASA Astrophysics Data System (ADS)

    Petukhov, A. M.; Soldatov, E. Yu

    2017-12-01

    Separation of electroweak component from strong component of associated Zγ production on hadron colliders is a very challenging task due to identical final states of such processes. The only difference is the origin of two leading jets in these two processes. Rectangular cuts on jet kinematic variables from ATLAS/CMS 8 TeV Zγ experimental analyses were improved using machine learning techniques. New selection variables were also tested. The expected significance of separation for LHC experiments conditions at the second datataking period (Run2) and 120 fb-1 amount of data reaches more than 5σ. Future experimental observation of electroweak Zγ production can also lead to the observation physics beyond Standard Model.

  19. 75 FR 43172 - Maternal, Infant, and Early Childhood Home Visiting Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... the evaluation results have been published in a peer-reviewed journal; or (bb) quasi-experimental... design (i.e. randomized controlled trial [RCT] or quasi-experimental design [QED]), level of attrition... a quasi-experimental design as a study design in which sample members are selected for the program...

  20. Cardiometabolic Syndrome in People With Spinal Cord Injury/Disease: Guideline-Derived and Nonguideline Risk Components in a Pooled Sample.

    PubMed

    Nash, Mark S; Tractenberg, Rochelle E; Mendez, Armando J; David, Maya; Ljungberg, Inger H; Tinsley, Emily A; Burns-Drecq, Patricia A; Betancourt, Luisa F; Groah, Suzanne L

    2016-10-01

    To assess cardiometabolic syndrome (CMS) risk definitions in spinal cord injury/disease (SCI/D). Cross-sectional analysis of a pooled sample. Two SCI/D academic medical and rehabilitation centers. Baseline data from subjects in 7 clinical studies were pooled; not all variables were collected in all studies; therefore, participant numbers varied from 119 to 389. The pooled sample included men (79%) and women (21%) with SCI/D >1 year at spinal cord levels spanning C3-T2 (American Spinal Injury Association Impairment Scale [AIS] grades A-D). Not applicable. We computed the prevalence of CMS using the American Heart Association/National Heart, Lung, and Blood Institute guideline (CMS diagnosis as sum of risks ≥3 method) for the following risk components: overweight/obesity, insulin resistance, hypertension, and dyslipidemia. We compared this prevalence with the risk calculated from 2 routinely used nonguideline CMS risk assessments: (1) key cut scores identifying insulin resistance derived from the homeostatic model 2 (HOMA2) method or quantitative insulin sensitivity check index (QUICKI), and (2) a cardioendocrine risk ratio based on an inflammation (C-reactive protein [CRP])-adjusted total cholesterol/high-density lipoprotein cholesterol ratio. After adjustment for multiple comparisons, injury level and AIS grade were unrelated to CMS or risk factors. Of the participants, 13% and 32.1% had CMS when using the sum of risks or HOMA2/QUICKI model, respectively. Overweight/obesity and (pre)hypertension were highly prevalent (83% and 62.1%, respectively), with risk for overweight/obesity being significantly associated with CMS diagnosis (sum of risks, χ(2)=10.105; adjusted P=.008). Insulin resistance was significantly associated with CMS when using the HOMA2/QUICKI model (χ(2)2=21.23, adjusted P<.001). Of the subjects, 76.4% were at moderate to high risk from elevated CRP, which was significantly associated with CMS determination (both methods; sum of risks, χ(2)2=10.198; adjusted P=.048 and HOMA2/QUICKI, χ(2)2=10.532; adjusted P=.04). As expected, guideline-derived CMS risk factors were prevalent in individuals with SCI/D. Overweight/obesity, hypertension, and elevated CRP were common in SCI/D and, because they may compound risks associated with CMS, should be considered population-specific risk determinants. Heightened surveillance for risk, and adoption of healthy living recommendations specifically directed toward weight reduction, hypertension management, and inflammation control, should be incorporated as a priority for disease prevention and management. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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