Infraclavicular versus axillary nerve catheters: A retrospective comparison of early catheter failure rate.

PubMed

Quast, Michaela B; Sviggum, Hans P; Hanson, Andrew C; Stoike, David E; Martin, David P; Niesen, Adam D

2018-05-01

Continuous brachial plexus catheters are often used to decrease pain following elbow surgery. This investigation aimed to assess the rate of early failure of infraclavicular (IC) and axillary (AX) nerve catheters following elbow surgery. Retrospective study. Postoperative recovery unit and inpatient hospital floor. 328 patients who received IC or AX nerve catheters and underwent elbow surgery were identified by retrospective query of our institution's database. Data collected included unplanned catheter dislodgement, catheter replacement rate, postoperative pain scores, and opioid administration on postoperative day 1. Catheter failure was defined as unplanned dislodging within 24 h of placement or requirement for catheter replacement and evaluated using a covariate adjusted model. 119 IC catheters and 209 AX catheters were evaluated. There were 8 (6.7%) failed IC catheters versus 13 (6.2%) failed AX catheters. After adjusting for age, BMI, and gender there was no difference in catheter failure rate between IC and AX nerve catheters (p = 0.449). These results suggest that IC and AX nerve catheters do not differ in the rate of early catheter failure, despite differences in anatomic location and catheter placement techniques. Both techniques provided effective postoperative analgesia with median pain scores < 3/10 for patients following elbow surgery. Reasons other than rate of early catheter failure should dictate which approach is performed. Copyright © 2018. Published by Elsevier Inc.

The influence of Y-TZP surface treatment on topography and ceramic/resin cement interfacial fracture toughness.

PubMed

Paes, P N G; Bastian, F L; Jardim, P M

2017-09-01

Consider the efficacy of glass infiltration etching (SIE) treatment as a procedure to modify the zirconia surface resulting in higher interfacial fracture toughness. Y-TZP was subjected to 5 different surface treatments conditions consisting of no treatment (G1), SIE followed by hydrofluoric acid treatment (G2), heat treated at 750°C (G3), hydrofluoric acid treated (G4) and airborne-particle abrasion with alumina particles (G5). The effect of surface treatment on roughness was evaluated by Atomic Force Microscopy providing three different parameters: R a , R sk and surface area variation. The ceramic/resin cement interface was analyzed by Fracture Mechanics K I test with failure mode determined by fractographic analysis. Weibull's analysis was also performed to evaluate the structural integrity of the adhesion zone. G2 and G4 specimens showed very similar, and high R a values but different surface area variation (33% for G2 and 13% for G4) and they presented the highest fracture toughness (K IC ). Weibull's analysis showed G2 (SIE) tendency to exhibit higher K IC values than the other groups but with more data scatter and a higher early failure probability than G4 specimens. Selective glass infiltration etching surface treatment was effective in modifying the zirconia surface roughness, increasing the bonding area and hence the mechanical imbrications at the zirconia/resin cement interface resulting in higher fracture toughness (K IC ) values with higher K IC values obtained when failure probability above 20% was expected (Weibull's distribution) among all the experimental groups. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Risk assessment for Industrial Control Systems quantifying availability using mean failure cost (MFC)

DOE PAGES

Chen, Qian; Abercrombie, Robert K; Sheldon, Frederick T.

2015-09-23

Industrial Control Systems (ICS) are commonly used in industries such as oil and natural gas, transportation, electric, water and wastewater, chemical, pharmaceutical, pulp and paper, food and beverage, as well as discrete manufacturing (e.g., automotive, aerospace, and durable goods.) SCADA systems are generally used to control dispersed assets using centralized data acquisition and supervisory control.Originally, ICS implementations were susceptible primarily to local threats because most of their components were located in physically secure areas (i.e., ICS components were not connected to IT networks or systems). The trend toward integrating ICS systems with IT networks (e.g., efficiency and the Internet ofmore » Things) provides significantly less isolation for ICS from the outside world thus creating greater risk due to external threats. Albeit, the availability of ICS/SCADA systems is critical to assuring safety, security and profitability. Such systems form the backbone of our national cyber-physical infrastructure.Herein, we extend the concept of mean failure cost (MFC) to address quantifying availability to harmonize well with ICS security risk assessment. This new measure is based on the classic formulation of Availability combined with Mean Failure Cost (MFC). Finally, the metric offers a computational basis to estimate the availability of a system in terms of the loss that each stakeholder stands to sustain as a result of security violations or breakdowns (e.g., deliberate malicious failures).« less

Field Programmable Gate Array Failure Rate Estimation Guidelines for Launch Vehicle Fault Tree Models

NASA Technical Reports Server (NTRS)

Al Hassan, Mohammad; Britton, Paul; Hatfield, Glen Spencer; Novack, Steven D.

2017-01-01

Today's launch vehicles complex electronic and avionics systems heavily utilize Field Programmable Gate Array (FPGA) integrated circuits (IC) for their superb speed and reconfiguration capabilities. Consequently, FPGAs are prevalent ICs in communication protocols such as MILSTD- 1553B and in control signal commands such as in solenoid valve actuations. This paper will identify reliability concerns and high level guidelines to estimate FPGA total failure rates in a launch vehicle application. The paper will discuss hardware, hardware description language, and radiation induced failures. The hardware contribution of the approach accounts for physical failures of the IC. The hardware description language portion will discuss the high level FPGA programming languages and software/code reliability growth. The radiation portion will discuss FPGA susceptibility to space environment radiation.

Taxonomy for Common-Cause Failure Vulnerability and Mitigation

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

Wood, Richard Thomas; Korsah, Kofi; Mullens, James Allen

2015-09-01

Applying current guidance and practices for common-cause failure (CCF) mitigation to digital instrumentation and control (I&C) systems has proven problematic, and the regulatory environment has been unpredictable. The potential for CCF vulnerability inhibits I&C modernization, thereby challenging the long-term sustainability of existing plants. For new plants and advanced reactor concepts, concern about CCF vulnerability in highly integrated digital I&C systems imposes a design burden that results in higher costs and increased complexity. The regulatory uncertainty in determining which mitigation strategies will be acceptable (e.g., what diversity is needed and how much is sufficient) drives designers to adopt complicated, costly solutionsmore » devised for existing plants. To address the conditions that constrain the transition to digital I&C technology by the US nuclear industry, crosscutting research is needed to resolve uncertainty, demonstrate necessary characteristics, and establish an objective basis for qualification of digital technology for nuclear power plant (NPP) I&C applications. To fulfill this research need, Oak Ridge National Laboratory is investigating mitigation of CCF vulnerability for nuclear-qualified applications. The outcome of this research is expected to contribute to a fundamentally sound, comprehensive basis to qualify digital technology for nuclear power applications. This report documents the development of a CCF taxonomy. The basis for the CCF taxonomy was generated by determining consistent terminology and establishing a classification approach. The terminology is based on definitions from standards, guides, and relevant nuclear power industry technical reports. The classification approach is derived from identified classification schemes focused on I&C systems and key characteristics, including failure modes. The CCF taxonomy provides the basis for a systematic organization of key systems aspects relevant to analyzing the potential for CCF vulnerability and the suitability of mitigation techniques. Development of an effective CCF taxonomy will help to provide a framework for establishing the objective analysis and assessment capabilities desired to facilitate rigorous identification of fault types and triggers that are the fundamental elements of CCF.« less

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

Field Programmable Gate Array Failure Rate Estimation Guidelines for Launch Vehicle Fault Tree Models

NASA Technical Reports Server (NTRS)

Al Hassan, Mohammad; Novack, Steven D.; Hatfield, Glen S.; Britton, Paul

2017-01-01

Today's launch vehicles complex electronic and avionic systems heavily utilize the Field Programmable Gate Array (FPGA) integrated circuit (IC). FPGAs are prevalent ICs in communication protocols such as MIL-STD-1553B, and in control signal commands such as in solenoid/servo valves actuations. This paper will demonstrate guidelines to estimate FPGA failure rates for a launch vehicle, the guidelines will account for hardware, firmware, and radiation induced failures. The hardware contribution of the approach accounts for physical failures of the IC, FPGA memory and clock. The firmware portion will provide guidelines on the high level FPGA programming language and ways to account for software/code reliability growth. The radiation portion will provide guidelines on environment susceptibility as well as guidelines on tailoring other launch vehicle programs historical data to a specific launch vehicle.

[Factors associated with the failure of Intermittent Preventive Treatment for malaria among pregnant women in Yaounde].

PubMed

Essiben, Félix; Foumane, Pascal; de Nguefack, Marcelle Aurelie Tsafack; Eko, Filbert Eko; Njotang, Philip Nana; Enow, Robinson Mbu; Mboudou, Emile Telesphore

2016-01-01

Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is recommended for malaria prevention during pregnancy. We investigated factors associated with the failure of this strategy. We conducted a case-control study in two health care facilities in Yaounde, from 1 May 2014 to 30 April 2015. Pregnant women treated with IPTp-SP, hospitalized for malaria and having a positive Rapid Diagnostic Test (RDT) result (case-subjects) were compared to pregnant women treated with IPTp-SP having a negative RDT result (control-subjects). Epi Info 7 software and SPSS 18.0 software were used with P< 0.05 as significance threshold. We recruited 234 subjects, 109 (46.6%) case-subjects and 125 control-subjects (53.4%). The associated factors found were: prematurity (P=0.03; OR=1.15; IC= 0.32 - 4.10), the non-use of LLIN (P=0.006; OR= 2.31; IC= 1.26 - 4.25), a history of hospitalization for malaria (P=0.007; OR= 2.19; IC= 1.23 - 3.89), IPTp-SP administration after 28 gestational weeks (P=0.001, OR= 3.55; IC= 1.7 - 7.61). After logistic regression, prematurity (P=0.024; OR=2.01; IC=1.1-3.7) and a history of hospitalization for malaria (P=0.001; OR=2.83; IC=1.50-5.4) remained associated with IPTp-SP failure. A history of hospitalization for malaria and prematurity are independent predictor of IPTp-SP failure.

The President and the Intelligence Community: The Importance of the Relationship

DTIC Science & Technology

2017-12-01

intelligence failures. Case studies are used to establish the character of the relationships between Presidents John F. Kennedy, George H. W. Bush, and...contribute to a working relationship strong enough to mitigate the risk of intelligence failures. Case studies are used to establish the character of...the president’s relationship with the IC as a whole?2 Then, through case study analysis, asks does a positive working relationship between the

Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study

PubMed Central

Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D.; Almagro-Garcia, Jacob; Neal, Aaron T.; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P.; Fairhurst, Rick M.

2017-01-01

Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong Subregion (GMS), emerging resistance to partner drugs in artemisinin combination therapies (ACTs) seriously threatens global efforts to treat and eliminate this disease. Molecular markers for ACT failure are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in Southeast Asia and beyond. Methods We performed a genome-wide association study (GWAS) of 297 P. falciparum isolates from Cambodia to investigate the relationship of 11,630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of dihydroartemisinin-piperaquine failures. We then performed a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Findings Piperaquine IC50s increased significantly from 2011 to 2013 in 3 Cambodian provinces. Genome-wide analysis of SNPs identified a chromosome 13 region that associates with elevated piperaquine IC50s. A nonsynonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin II and plasmepsin III genes on chromosome 14 also associate with elevated piperaquine IC50s. After adjusting for covariates, both exo-E415G and plasmepsin II-III markers significantly associate with decreased treatment efficacy (0.38 and 0.41 survival rates, respectively). Interpretation The exo-E415G SNP and plasmepsin II-III amplification are markers of piperaquine resistance and dihydroartemisinin-piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into GMS countries, and elucidate the mechanism of piperaquine resistance. Since plasmepsins are involved in the parasite’s haemoglobin-to-haemozoin conversion pathway, targeted by related antimalarials, plasmepsin II-III amplification likely mediates piperaquine resistance. Funding Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health; Wellcome Trust; Bill and Melinda Gates Foundation; Medical Research Council; and UK Department for International Development. PMID:27818095

External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer

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

Reddy, Abhinav V.; Christodouleas, John P.; Wu, Tianming

Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported intomore » a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.« less

Pulsed laser ablation of IC packages for device failure analyses

NASA Astrophysics Data System (ADS)

Hong, Ming Hui; Mai, ZhiHong; Chen, G. X.; Thiam, Thomas; Song, Wen D.; Lu, Yongfeng; Soh, Chye E.; Chong, Tow Chong

2002-06-01

Pulsed laser ablation of mold compounds for IC packaging in air and with steam assistance is investigated. It is applied to decap IC packages and expose computer CPU dies for the device failure analyses. Compared with chemical decapping, the laser ablation has advantages of being fast speed, non- contact and dry processing. Laser ablation with the steam assistance results in higher ablation rate and wider ablated crater with much smoother surface morphology. It implies that the steam assisted laser ablation can achieve a faster and better quality laser processing. Audible acoustic wave and plasma optical signal diagnostics are also carried out to have a better understanding of the mechanisms behind. Light wavelength and laser fluence applied in the decapping are two important parameters. The 532 nm Nd:YAG laser decapping at a low laser fluence can achieve a large decapping area with a fine ablation profile. IC packages decapped by the laser ablation show good quality for the device failure analyses.

Mechanical properties of zirconia reinforced lithium silicate glass-ceramic.

PubMed

Elsaka, Shaymaa E; Elnaghy, Amr M

2016-07-01

The aim of this study was to assess the mechanical properties of recently introduced zirconia reinforced lithium silicate glass-ceramic. Two types of CAD/CAM glass-ceramics (Vita Suprinity (VS); zirconia reinforced lithium silicate and IPS e.max CAD (IC); lithium disilicate) were used. Fracture toughness, flexural strength, elastic modulus, hardness, brittleness index, and microstructures were evaluated. Data were analyzed using independent t tests. Weibull analysis of flexural strength data was also performed. VS had significantly higher fracture toughness (2.31±0.17MPam(0.5)), flexural strength (443.63±38.90MPa), elastic modulus (70.44±1.97GPa), and hardness (6.53±0.49GPa) than IC (P<0.001). On the other hand, VS glass-ceramic revealed significantly a higher brittleness index (2.84±0.26μm(-1/2)) (lower machinability) than IC glass-ceramic (P<0.05). VS demonstrated a homogeneous fine crystalline structure while, IC revealed a structure with needle-shaped fine-grained crystals embedded in a glassy matrix. The VS glass-ceramic revealed a lower probability of failure and a higher strength than IC glass-ceramic according to Weibull analysis. The VS zirconia reinforced lithium silicate glass-ceramic revealed higher mechanical properties compared with IC lithium disilicate glass-ceramic. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

JANNAF Lessons Learned Panel Discussion

NASA Technical Reports Server (NTRS)

Richards, Steve

2010-01-01

The difference between the AS-510 observed and predicted separation distance is attributed to a greater F-1 engine "tail off" impulse than that used in the separation distance prediction. . The F-1 thrust decay was normal and not appreciably different from previous (AS-505 through 509) flights. . Analysis indicates that with an S-IC stage having only four retro motors, failure of one retro motor to ignite would result in marginal separation distances and, in the 3-sigma case, re-contact of the two stages. . S-IC-11 and subsequent flight stages were equipped with eight retro motors rather than the planned four.

Effect of Joule heating and current crowding on electromigration in mobile technology

NASA Astrophysics Data System (ADS)

Tu, K. N.; Liu, Yingxia; Li, Menglu

2017-03-01

In the present era of big data and internet of things, the use of microelectronic products in all aspects of our life is manifested by the ubiquitous presence of mobile devices as i-phones and wearable i-products. These devices are facing the need for higher power and greater functionality applications such as in i-health, yet they are limited by physical size. At the moment, software (Apps) is much ahead of hardware in mobile technology. To advance hardware, the end of Moore's law in two-dimensional integrated circuits can be extended by three-dimensional integrated circuits (3D ICs). The concept of 3D ICs has been with us for more than ten years. The challenge in 3D IC technology is dense packing by using both vertical and horizontal interconnections. Mass production of 3D IC devices is behind schedule due to cost because of low yield and uncertain reliability. Joule heating is serious in a dense structure because of heat generation and dissipation. A change of reliability paradigm has advanced from failure at a specific circuit component to failure at a system level weak-link. Currently, the electronic industry is introducing 3D IC devices in mainframe computers, where cost is not an issue, for the purpose of collecting field data of failure, especially the effect of Joule heating and current crowding on electromigration. This review will concentrate on the positive feedback between Joule heating and electromigration, resulting in an accelerated system level weak-link failure. A new driving force of electromigration, the electric potential gradient force due to current crowding, will be reviewed critically. The induced failure tends to occur in the low current density region.

"Watching time tick by…": Decision making for Duchenne muscular dystrophy trials.

PubMed

Peay, Holly L; Scharff, Hadar; Tibben, Aad; Wilfond, Benjamin; Bowie, Janice; Johnson, Joanna; Nagaraju, Kanneboyina; Escolar, Diana; Piacentino, Jonathan; Biesecker, Barbara B

2016-01-01

This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

PubMed

Auzinger, Georg; Playford, E Geoffrey; Graham, Christopher N; Knox, Hediyyih N; Weinstein, David; Kantecki, Michal; Schlamm, Haran; Charbonneau, Claudie

2015-10-26

Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness. From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

Experimentally Observed Electrical Durability of 4H-SiC JFET ICs Operating from 500 C to 700 C

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Spry, David J.; Chen, Liangyu; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2016-01-01

This ECSCRM 2016 submission presents further electrical testing and microscopic post-failure studies aimed at more comprehensive understanding of the durability limits of this extreme temperature IC technology. The results summarized represent an unprecedented combination of T 500 C semiconductor IC durability and functionality.

Elevated voltage level I{sub DDQ} failure testing of integrated circuits

DOEpatents

Righter, A.W.

1996-05-21

Burn in testing of static CMOS IC`s is eliminated by I{sub DDQ} testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip. 4 figs.

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

PubMed Central

Buiting, K; Dittrich, B; Gross, S; Lich, C; Färber, C; Buchholz, T; Smith, E; Reis, A; Bürger, J; Nöthen, M M; Barth-Witte, U; Janssen, B; Abeliovich, D; Lerer, I; van den Ouweland, A M; Halley, D J; Schrander-Stumpel, C; Smeets, H; Meinecke, P; Malcolm, S; Gardner, A; Lalande, M; Nicholls, R D; Friend, K; Schulze, A; Matthijs, G; Kokkonen, H; Hilbert, P; Van Maldergem, L; Glover, G; Carbonell, P; Willems, P; Gillessen-Kaesbach, G; Horsthemke, B

1998-01-01

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint. PMID:9634532

Molecular Hydrogen Fluorescence in IC 63

NASA Technical Reports Server (NTRS)

Andersson, B-G

2005-01-01

This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

Challenges in Resolution for IC Failure Analysis

NASA Astrophysics Data System (ADS)

Martinez, Nick

1999-10-01

Resolution is becoming more and more of a challenge in the world of Failure Analysis in integrated circuits. This is a result of the ongoing size reduction in microelectronics. Determining the cause of a failure depends upon being able to find the responsible defect. The time it takes to locate a given defect is extremely important so that proper corrective actions can be taken. The limits of current microscopy tools are being pushed. With sub-micron feature sizes and even smaller killing defects, optical microscopes are becoming obsolete. With scanning electron microscopy (SEM), the resolution is high but the voltage involved can make these small defects transparent due to the large mean-free path of incident electrons. In this presentation, I will give an overview of the use of inspection methods in Failure Analysis and show example studies of my work as an Intern student at Texas Instruments. 1. Work at Texas Instruments, Stafford, TX, was supported by TI. 2. Work at Texas Tech University, was supported by NSF Grant DMR9705498.

TU-FG-201-01: 18-Month Clinical Experience of a Linac Daily Quality Assurance (QA) Solution Using Only EPID and OBI

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

Cai, B; Sun, B; Yaddanapudi, S

Purpose: To describe the clinical use of a Linear Accelerator (Linac) DailyQA system with only EPID and OBI. To assess the reliability over an 18-month period and improve the robustness of this system based on QA failure analysis. Methods: A DailyQA solution utilizing an in-house designed phantom, combined EPID and OBI image acquisitions, and a web-based data analysis and reporting system was commissioned and used in our clinic to measure geometric, dosimetry and imaging components of a Varian Truebeam Linac. During an 18-month period (335 working days), the Daily QA results, including the output constancy, beam flatness and symmetry, uniformity,more » TPR20/10, MV and KV imaging quality, were collected and analyzed. For output constancy measurement, an independent monthly QA system with an ionization chamber (IC) and annual/incidental TG51 measurements with ADCL IC were performed and cross-compared to Daily QA system. Thorough analyses were performed on the recorded QA failures to evaluate the machine performance, optimize the data analysis algorithm, adjust the tolerance setting and improve the training procedure to prevent future failures. Results: A clinical workflow including beam delivery, data analysis, QA report generation and physics approval was established and optimized to suit daily clinical operation. The output tests over the 335 working day period cross-correlated with the monthly QA system within 1.3% and TG51 results within 1%. QA passed with one attempt on 236 days out of 335 days. Based on the QA failures analysis, the Gamma criteria is revised from (1%, 1mm) to (2%, 1mm) considering both QA accuracy and efficiency. Data analysis algorithm is improved to handle multiple entries for a repeating test. Conclusion: We described our 18-month clinical experience on a novel DailyQA system using only EPID and OBI. The long term data presented demonstrated the system is suitable and reliable for Linac daily QA.« less

Experimental Durability Testing of 4H SiC JFET Integrated Circuit Technology at 727 C

NASA Technical Reports Server (NTRS)

Spry, David; Neudeck, Phil; Chen, Liangyu; Chang, Carl; Lukco, Dorothy; Beheim, Glenn M

2016-01-01

We have reported SiC integrated circuits (IC's) with two levels of metal interconnect that have demonstrated prolonged operation for thousands of hours at their intended peak ambient operational temperature of 500 C [1, 2]. However, it is recognized that testing of semiconductor microelectronics at temperatures above their designed operating envelope is vital to qualification. Towards this end, we previously reported operation of a 4H-SiC JFET IC ring oscillator on an initial fast thermal ramp test through 727 C [3]. However, this thermal ramp was not ended until a peak temperature of 880 C (well beyond failure) was attained. Further experiments are necessary to better understand failure mechanisms and upper temperature limit of this extreme-temperature capable 4H-SiC IC technology. Here we report on additional experimental testing of custom-packaged 4H-SiC JFET IC devices at temperatures above 500 C. In one test, the temperature was ramped and then held at 727 C, and the devices were periodically measured until electrical failure was observed. A 4H-SiC JFET on this chip electrically functioned with little change for around 25 hours at 727 C before rapid increases in device resistance caused failure. In a second test, devices from our next generation 4H-SiC JFET ICs were ramped up and then held at 700 C (which is below the maximum deposition temperature of the dielectrics). Three ring oscillators functioned for 8 hours at this temperature before degradation. In a third experiment, an alternative die attach of gold paste and package lid was used, and logic circuit operation was demonstrated for 143.5 hours at 700 C.

Experimental Durability Testing of 4H SiC JFET Integrated Circuit Technology at 727 Degrees Centigrade

NASA Technical Reports Server (NTRS)

Spry, David J.; Neudeck, Philip G.; Chen, Liangyu; Chang, Carl W.; Lukco, Dorothy; Beheim, Glenn M.

2016-01-01

We have reported SiC integrated circuits (ICs) with two levels of metal interconnect that have demonstrated prolonged operation for thousands of hours at their intended peak ambient operational temperature of 500 degrees Centigrade. However, it is recognized that testing of semiconductor microelectronics at temperatures above their designed operating envelope is vital to qualification. Towards this end, we previously reported operation of a 4H-SiC JFET IC ring oscillator on an initial fast thermal ramp test through 727 degrees Centigrade. However, this thermal ramp was not ended until a peak temperature of 880 degrees Centigrade (well beyond failure) was attained. Further experiments are necessary to better understand failure mechanisms and upper temperature limit of this extreme-temperature capable 4H-SiC IC technology.Here we report on additional experimental testing of custom-packaged 4H-SiC JFET IC devices at temperatures above 500 degrees Centigrade. In one test, the temperature was ramped and then held at 727 degrees Centigrade, and the devices were periodically measured until electrical failure was observed. A 4H-SiC JFET on this chip electrically functioned with little change for around 25 hours at 727 degrees Centigrade before rapid increases in device resistance caused failure. In a second test, devices from our next generation 4H-SiC JFET ICs were ramped up and then held at 700 degrees Centigrade (which is below the maximum deposition temperature of the dielectrics). Three ring oscillators functioned for 8 hours at this temperature before degradation. In a third experiment, an alternative die attach of gold paste and package lid was used, and logic circuit operation was demonstrated for 143.5 hours at 700 degrees Centigrade.

Apparatus and method for defect testing of integrated circuits

DOEpatents

Cole, Jr., Edward I.; Soden, Jerry M.

2000-01-01

An apparatus and method for defect and failure-mechanism testing of integrated circuits (ICs) is disclosed. The apparatus provides an operating voltage, V.sub.DD, to an IC under test and measures a transient voltage component, V.sub.DDT, signal that is produced in response to switching transients that occur as test vectors are provided as inputs to the IC. The amplitude or time delay of the V.sub.DDT signal can be used to distinguish between defective and defect-free (i.e. known good) ICs. The V.sub.DDT signal is measured with a transient digitizer, a digital oscilloscope, or with an IC tester that is also used to input the test vectors to the IC. The present invention has applications for IC process development, for the testing of ICs during manufacture, and for qualifying ICs for reliability.

[Salvage cryotherapy of prostate cancer after failed external radiotherapy and brachytherapy: Morbidity and mid-term oncological results].

PubMed

Gevorgyan, A; Hétet, J-F; Robert, M; Duchattelle-Dussaule, V; Corno, L; Boulay, I; Baumert, H

2018-04-01

To study the oncologic and functional results of salvage cryotherapy after failure of external radiotherapy and brachytherapy. Patients treated by total salvage cryotherapy (3rd generation) in 2 centers (Groupe Hospitalier Saint-Joseph in Paris and Clinique Jule-Verne Nantes) in between January 2008 and April 2016 were included. The biochemical recurrence-free survival (BRFS) was calculated using the Phoenix criteria (PSA>nadir+2ng/mL). The functional results were assessed clinically. Ninety-seven patients with an average follow up of 39.4months were evaluated retrospectively. The 5-year biochemical recurrence-free survival (5y-BRFS) among all patients was 58.1% (IC à 95% [45.9-68.5]). Low and intermediate risk patients (d'Amico classification) were less prone to biochemical recurrence than high risk (81.05% (IC à 95% [64.1-90.5]) 5y-BRFS as opposed to 35.09% (IC à 95% [20.1-50.4]) respectively) (P<0.0001). As were patients with a Gleason score≤7 75.35% (IC à 95% [59.7-85.6]) compared to 32.31% (IC à 95% [16.5-49.2]) for higher Gleason (>7 scores [P=0.0002]). A Gleason score>7 (OR=6.9; P=0.002), PSA nadir>1ng/mL (OR=25.8; P=0.0026) and peri-urethral invasion (OR=35.8; P<0.001) were major risk factors for local recurrence in univariate analysis. In multivariate analysis, only PSA nadir>1ng/mL (OR=12.9; P=0.042) and peri-urethral invasion (OR=21.6; P=0.0003) remain major risk factors for recurrence. About 13 (16.46%) patients were incontinent of which 3 (3.79%) required placement of an artificial urinary sphincter. Erectile dysfunction was present in 66 (83.5%) patients. Recto-urethral fistula was uncommon in 1 patient (1.27%). Salvage cryotherapy after failure of external radiotherapy and brachytherapy is a reliable and reproducible technique with promising oncological and functional results. Study of prognostic factors will help better select eligible patients in the future. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Lessons From Love Canal: Considerations for the Effective Use of Institutional Controls

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

Fil, Richard M.

The purpose of this paper is to provide background on a well-known failure of an institutional control (IC), an overview of the types and potential shortcomings of individual ICs, provide some considerations for more effectively selecting and maintaining appropriate ICs in the context of a decommissioning project (including those that may be subject to various federal and state requirements). In light of these considerations, it should be clear that the potential liabilities arising from the failure to comply with ICs may be very significant, even if such failure is not directly caused by the party responsible for the pre-existing conditions.more » A number of options exist to help manage risk at sites where impacts will remain in place following the completion of active decommissioning efforts. It is important to involve all appropriate professionals early on and throughout the process and to consult with other relevant parties (e.g., regulatory agencies, the community, and potential site owners and occupants) to evaluate the most appropriate ICs available. This is particularly critical in the context of a long-term decommissioning project involving a large number of contractors, personnel turnover or departure, potential isolation of individuals with focused technical or regulatory expertise, or other factors that may affect more ideal communication. Mechanisms for ensuring long-term compliance with ICs, as well as reliable approaches for enforcing their terms, also warrant early and on-going attention. However, even with a detailed and thoughtful approach, it must be recognized under certain circumstances that a more realistic goal may be to continue to reasonably minimize potential risks rather than absolutely avoid all risks for all time.« less

Assessment of biological, psychological and adherence factors in the prediction of step-down treatment for patients with well-controlled asthma.

PubMed

Saito, N; Kamata, A; Itoga, M; Tamaki, M; Kayaba, H; Ritz, T

2017-04-01

Inhaled corticosteroids (ICS) and inhaled corticosteroids combined with long-acting beta2-agonist (ICS/LABA) are standard treatments for asthma. However, factors that might help reduce medication in well-controlled asthma are unknown. We classified problems of asthma patients into biological, psychological and adherence factors, and investigated factors associated with the indication and failure of a medication step-down treatment. Two hundred twenty two well-controlled asthma patients receiving ICS or ICS/LABA were assessed for physical and psychiatric problems and followed up for one year from adjustment of their treatment step. Factor B was defined as a presence of chronic upper airway complications. Factor P was defined as presence of psychiatric complications such as sleep disorder, depression, anxiety and somatoform disorders. Factor A was defined as poor adherence to ICS or ICS/LABA inhaler of 75% or less. Success in step-down treatment was defined as maintenance of well-controlled status for over one year after step-down. Factor B was the most important single negative predictive factor for indication for step-down treatment (Odds ratio; 0.19). Factor A increased the risk of failure to maintain step-down treatment most significantly by 23-fold, and factor B increased it by 11-fold. The combination of factors B and A increased failure by 24-fold, factors P and A by 21-fold, all three factors by 36-fold. Factor P only interacted with the other factors to reduce chances of stepping down, but did not constitute a problem factor when present alone. The evaluation of biological, psychological and adherence problems may lead to a more proactive and targeted approach to step-down treatment for patients with well-controlled asthma. © 2017 John Wiley & Sons Ltd.

Measure of chest wall thickness in French soldiers: which technique to use for needle decompression of tension pneumothorax at the front?

PubMed

Lamblin, Antoine; Turc, Jean; Bylicki, Olivier; Lohéas, Damien; Martinez, Jean-Yves; Derkenne, Clément; Wey, Pierre-François; Précloux, Pascal

2014-07-01

Needle decompression of tension pneumothorax in soldiers of the French infantry has a risk for failure when the standard procedure that involves the insertion of a 14-gauge, 5-cm catheter into the 2nd intercostal space (ICS) is used. This study measured the chest wall thickness (CWT) to assess whether this approach is appropriate. CWT was measured by ultrasound in 122 French soldiers at the 2nd and 4th ICSs on both the right and left sides. CWT was measured at 4.19 cm (± 0.96 cm) at the 2nd ICS and 3.00 cm (± 0.91 cm) at the 4th ICS (p < 0.001). CWT was greater than 5 cm in 24.2% of cases at the 2nd ICS and 4.9% of cases at the 4th ICS (p < 0.001). This study suggests a high risk of failure when using the technique currently taught in the French army. A lateral approach into the 4th ICS could decrease this risk. The results of this study must be validated in patients presenting tension pneumothorax. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Keeping Up with Healthcare Trends: IcHeart as a Medication Management Application

NASA Astrophysics Data System (ADS)

Kasinathan, Vinothini; Mustapha, Aida; Azah Samsudin, Noor

2016-11-01

According to the US governments, more than 125,000 people die each year due to failure to manage their medications, leading to approximately USD100 billion in preventable costs to healthcare systems. The core failure in medication management is attributed by patients failing to adhere their medication regimens, whether by accident, negligence, or intentional. Recognizing the importants of vigilant monitoring in medication management, this paper is set to review the latest android-based healthcare trends and propose a new mobile medication reminder application called IcHeart.

Embracing the Devil: An Analysis of the Formal Adoption of Red Teaming in the Security Planning for Major Events

DTIC Science & Technology

2017-03-01

little hope of a better solution, low self - esteem temporarily induced by recent failures, and difficulties in determining feasible alternatives in...The ability to think creatively and communicate potentially negative findings effectively are unique skills improved with formal training and...Homeland Security Presidential Directive IC intelligence community IED improvised explosive device JCCIC Joint Congressional Committee on

Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy.

PubMed

Farooq, Umar; Maurer, Matthew J; Thompson, Carrie A; Thanarajasingam, Gita; Inwards, David J; Micallef, Ivana; Macon, William; Syrbu, Sergei; Lin, Tasha; Lin, Yi; Ansell, Stephen M; Nowakowski, Grzegorz S; Habermann, Thomas M; Cerhan, James R; Link, Brian K

2017-10-01

This study aimed to describe the patterns of care and outcomes of diffuse large B cell lymphoma (DLBCL) after failure of front line anthracycline-based immunochemotherapy (IC). Patients with newly diagnosed lymphoma were prospectively enrolled in Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellzence. All DLBCL and primary mediastinal B-cell lymphoma (PMBL) patients treated with front-line anthracycline-based IC were followed for relapse. Patients with relapse on follow-up and subsequently retreated were included in this analysis. 1039 patients received anthracycline-based IC between 2002 and 2012, of which 244 relapsed and were subsequently retreated. Across all therapies, overall survival at 4 years (OS4) from relapse was 28% and 103 patients ultimately underwent autologous haematopoietic cell transplant (autoHCT) with OS4 from autoHCT of 51%. Patients relapsing after 12 months from initial diagnosis had OS4 of 47% but those with a transient or no response to initial therapy had OS4 of only 13%. Outcomes of relapsed or refractory DLBCL differ substantially when categorized by response to initial therapy, timing of relapse and opportunity to undergo autoHCT. The design and interpretation of uncontrolled trials should account for this heterogeneity in patients with relapsed DLBCL. © 2017 John Wiley & Sons Ltd.

Unit-Sphere Multiaxial Stochastic-Strength Model Applied to Anisotropic and Composite Materials

NASA Technical Reports Server (NTRS)

Nemeth, Noel, N.

2013-01-01

Models that predict the failure probability of brittle materials under multiaxial loading have been developed by authors such as Batdorf, Evans, and Matsuo. These "unit-sphere" models assume that the strength-controlling flaws are randomly oriented, noninteracting planar microcracks of specified geometry but of variable size. This methodology has been extended to predict the multiaxial strength response of transversely isotropic brittle materials, including polymer matrix composites (PMCs), by considering (1) flaw-orientation anisotropy, whereby a preexisting microcrack has a higher likelihood of being oriented in one direction over another direction, and (2) critical strength, or K (sub Ic) orientation anisotropy, whereby the level of critical strength or fracture toughness for mode I crack propagation, K (sub Ic), changes with regard to the orientation of the microstructure. In this report, results from finite element analysis of a fiber-reinforced-matrix unit cell were used with the unit-sphere model to predict the biaxial strength response of a unidirectional PMC previously reported from the World-Wide Failure Exercise. Results for nuclear-grade graphite materials under biaxial loading are also shown for comparison. This effort was successful in predicting the multiaxial strength response for the chosen problems. Findings regarding stress-state interactions and failure modes also are provided.

Elevated voltage level I.sub.DDQ failure testing of integrated circuits

DOEpatents

Righter, Alan W.

1996-01-01

Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

Growth impairment due to transient hypercortisolism.

PubMed

Armour, K; Chalew, S; Kowarski, A A

1986-01-01

Cushing's syndrome in childhood is generally recognized by classical features such as truncal obesity, striae, easy bruising, moon facies, hypertension and growth retardation. Exceptionally, Cushing's syndrome has been reported to present as growth failure alone. We diagnosed transient hypercortisolism in 6 children who had poor growth as their only presenting abnormality. The 6 children all had integrated concentrations of cortisols (IC-F) (14.1 +/- 1.7 micrograms/dl; mean +/- 1 SD) which exceeded the IC-F in healthy children and adults (5.7 +/- 1.5 micrograms/dl; P less than 0.001). The IC-F of these 6 index cases overlapped the range of IC-F in patients with pathologically proven Cushing's syndrome (20.2 +/- 4.7 micrograms/dl). Four of the 6 patients were treated with human growth hormone for 8 months and showed a marked improvement in their growth rates. Four patients have entered puberty and are growing at normal rates. Three of the 6 children had normal repeat IC-Fs, subsequently, at a time they had normal growth rates. In 1-1/2 to 3 years of follow-up, none of the patients developed any other stigmata of Cushing's syndrome. We conclude that transient hypercortisolism, documented by the IC-F, may cause growth failure without other symptoms of Cushing's syndrome. Growth hormone therapy may improve the growth rate of these children at the time of their poor growth.

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

O'Hara, J.M.; W. Gunther, G. Martinez-Guridi

New and advanced reactors will use integrated digital instrumentation and control (I&C) systems to support operators in their monitoring and control functions. Even though digital systems are typically highly reliable, their potential for degradation or failure could significantly affect operator performance and, consequently, impact plant safety. The U.S. Nuclear Regulatory Commission (NRC) supported this research project to investigate the effects of degraded I&C systems on human performance and plant operations. The objective was to develop human factors engineering (HFE) review guidance addressing the detection and management of degraded digital I&C conditions by plant operators. We reviewed pertinent standards and guidelines,more » empirical studies, and plant operating experience. In addition, we conducted an evaluation of the potential effects of selected failure modes of the digital feedwater system on human-system interfaces (HSIs) and operator performance. The results indicated that I&C degradations are prevalent in plants employing digital systems and the overall effects on plant behavior can be significant, such as causing a reactor trip or causing equipment to operate unexpectedly. I&C degradations can impact the HSIs used by operators to monitor and control the plant. For example, sensor degradations can make displays difficult to interpret and can sometimes mislead operators by making it appear that a process disturbance has occurred. We used the information obtained as the technical basis upon which to develop HFE review guidance. The guidance addresses the treatment of degraded I&C conditions as part of the design process and the HSI features and functions that support operators to monitor I&C performance and manage I&C degradations when they occur. In addition, we identified topics for future research.« less

Effects of prenatal substance exposure on neurocognitive correlates of inhibitory control success and failure.

PubMed

Roos, Leslie E; Beauchamp, Kathryn G; Pears, Katherine C; Fisher, Philip A; Berkman, Elliot T; Capaldi, Deborah

2017-01-01

Adolescents with prenatal substance (drug and alcohol) exposure exhibit inhibitory control (IC) deficits and aberrations in associated neural function. Nearly all research to date examines exposure to individual substances, and a minimal amount is known about the effects of heterogeneous exposure-which is more representative of population exposure levels. Using functional magnetic resonance imaging (fMRI), we investigated IC (Go/NoGo) in heterogeneously exposed (n = 7) vs. control (n = 7) at-risk adolescents (ages 13-17). The fMRI results indicated multiple IC processing differences consistent with a more immature developmental profile for exposed adolescents (Exposed  >  Nonexposed: NoGo > Go: right ventrolateral prefrontal cortex, right cuneus, and left inferior parietal lobe; NoGo > false alarm: occipital lobe; Go > false alarm: right anterior prefrontal cortex). Simple effects suggest exposed adolescents exhibited exaggerated correct trial but decreased incorrect trial activation. Results provide initial evidence that prenatal exposure across substances creates similar patterns of atypical brain activation to IC success and failure.

Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study.

PubMed

Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D; Almagro-Garcia, Jacob; Neal, Aaron T; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P; Fairhurst, Rick M

2017-02-01

As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC 50 s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine. We then did a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Piperaquine IC 50 s increased significantly from 2011 to 2013 in three Cambodian provinces (2011 vs 2013 median IC 50 s: 20·0 nmol/L [IQR 13·7-29·0] vs 39·2 nmol/L [32·8-48·1] for Ratanakiri, 19·3 nmol/L [15·1-26·2] vs 66·2 nmol/L [49·9-83·0] for Preah Vihear, and 19·6 nmol/L [11·9-33·9] vs 81·1 nmol/L [61·3-113·1] for Pursat; all p≤10 -3 ; Kruskal-Wallis test). Genome-wide analysis of SNPs identified a chromosome 13 region that associates with raised piperaquine IC 50 s. A non-synonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin 2 and plasmepsin 3 genes on chromosome 14 also associate with raised piperaquine IC 50 s. After adjusting for covariates, both exo-E415G and plasmepsin 2-3 markers significantly associate (p=3·0 × 10 -8 and p=1·7 × 10 -7 , respectively) with decreased treatment efficacy (survival rates 0·38 [95% CI 0·25-0·51] and 0·41 [0·28-0·53], respectively). The exo-E415G SNP and plasmepsin 2-3 amplification are markers of piperaquine resistance and dihydroartemisinin-piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into other countries of the Greater Mekong subregion, and elucidate the mechanism of piperaquine resistance. Since plasmepsins are involved in the parasite's haemoglobin-to-haemozoin conversion pathway, targeted by related antimalarials, plasmepsin 2-3 amplification probably mediates piperaquine resistance. Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and UK Department for International Development. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Aggressive Behaviors in Young Siblings: Associations with Executive Functions and Maternal Characteristics.

PubMed

Spann, Catherine A; Gagne, Jeffrey R

2016-04-01

Aggressive behaviors in early childhood are associated with multiple undesirable outcomes, including juvenile delinquency, academic failure, and substance abuse. This investigation employed a family study design to examine child, mother and sibling predictors of early-emerging aggressive behaviors. These predictors included several indices of executive functioning within children, depression symptoms and education level of mothers, and inhibitory control (IC) of siblings. The sample consisted of 95 families (191 children; boys = 100) with at least two, typically developing children between 30 and 66 months of age (M(age) = 45.93 months, SD = 12.40). Measures included laboratory-assessed working memory and IC, parent-reported aggressive behaviors, as well as self-reported maternal depression symptoms and education. Results revealed that children showed substantial sibling similarity in aggressive behaviors. Using multilevel regression analyses, low child IC and greater maternal depression symptoms were associated with increased child aggressive behaviors. Child working memory, maternal education, and sibling IC did not uniquely predict child aggressive behaviors. Moderation analyses revealed an interaction between maternal depression symptoms and maternal education, such that the effect of depression symptoms on child aggressive behaviors was particularly evident amongst highly educated mothers. The current analysis moved beyond a main effects model of maternal depression and extended previous findings on the importance of child IC to aggressive behaviors by using a multiple-child-per-family framework. A promising direction for future research includes assessing whether efforts to increase child IC are successful in reducing child aggressive behaviors.

Failure Mechanisms of GaAs Transistors - A Literature Survey

DTIC Science & Technology

1990-03-01

doping profile cannot be as sharp as with epitaxial methods. This is the result of the statistics of the implantation and the general diffusion that...Speed GaAs Logic Gates 5.1 GaAs PLANAR TRANSITOR STRUCTURES USED IN IC’S Some planar transistor structures used in IC’s with examples of the

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study)

PubMed Central

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa

2017-01-01

ABSTRACT An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated (P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. PMID:28659321

Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

PubMed

Cohen, Ezra E W; Karrison, Theodore G; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H; Brockstein, Bruce E; Agulnik, Mark B; Mittal, Bharat B; Yunus, Furhan; Samant, Sandeep; Raez, Luis E; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y; Villaflor, Victoria M; Haraf, Daniel J; Vokes, Everett E

2014-09-01

Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. © 2014 by American Society of Clinical Oncology.

Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

PubMed Central

Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

2014-01-01

Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

Non-Invasive Ventilation in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

PubMed

Bittencourt, Hugo Souza; Reis, Helena França Correia Dos; Lima, Melissa Santos; Gomes, Mansueto

2017-02-01

Non-invasive ventilation (NIV) may perfect respiratory and cardiac performance in patients with heart failure (HF). The objective of the study to establish, through systematic review and meta-analysis, NIV influence on functional capacity of HF patients. A systematic review with meta-analysis of randomized studies was carried out through research of databases of Cochrane Library, SciELO, Pubmed and PEDro, using the key-words: heart failure, non-invasive ventilation, exercise tolerance; and the free terms: bi-level positive airway pressure (BIPAP), continuous positive airway pressure (CPAP), and functional capacity (terms were searched for in English and Portuguese) using the Boolean operators AND and OR. Methodological quality was ensured through PEDro scale. Weighted averages and a 95% confidence interval (CI) were calculated. The meta-analysis was done thorugh the software Review Manager, version 5.3 (Cochrane Collaboration). Four randomized clinical trials were included. Individual studies suggest NIV improved functional capacity. NIV resulted in improvement in the distance of the six-minute walk test (6MWT) (68.7m 95%CI: 52.6 to 84.9) in comparison to the control group. We conclude that the NIV is an intervention that promotes important effects in the improvement of functional capacity of HF patients. However, there is a gap in literature on which are the most adequate parameters for the application of this technique. Resumo A ventilação não invasiva (VNI) pode aperfeiçoar o desempenho cardíaco e respiratório dos pacientes com insuficiência cardíaca (IC). O objetivo do estudo é estabelecer, por meio de revisão sistemática e meta-análise, a influência da VNI na capacidade funcional (CF) de indivíduos com IC. Foi realizada uma revisão sistemática com meta-análise de estudos randomizados através da pesquisa nas bases de dados Biblioteca Cochrane, SciELO, Pubmed e PEDro, utilizando-se as palavras-chave: insuficiência cardíaca, ventilação não invasiva, tolerância ao exercício; e os termos livres: pressão positiva em dois níveis nas vias aéreas (BIPAP), pressão positiva contínua em vias aéreas (CPAP), CF e seus correlatos na língua inglesa, com a combinação dos operadores booleanos (AND e OR). A avaliação da qualidade metodológica se deu via escala de PEDro. Foram calculadas as médias ponderadas e o intervalo de confiança (IC) de 95%. Meta-análise foi realizada com software Review Manager versão 5.3 (Colaboração Cochrane). Foram incluídos quatro ensaios clínicos randomizados. Estudos individuais sugerem que a VNI contribuiu para melhora da CF. VNI resultou em melhora na distância do teste de caminhada de seis minutos (TC6) (68,7m 95% IC: 52,6 a 84,9) comparado ao grupo controle. Concluimos que a VNI é uma intervenção que promove efeitos importantes na melhora da CF de pacientes com IC. No entanto, há uma lacuna na literatura de quais são os parâmetros mais adequados para aplicação dessa técnica.

A Summary of Taxonomies of Digital System Failure Modes Provided by the DigRel Task Group

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

Chu T. L.; Yue M.; Postma, W.

2012-06-25

Recently, the CSNI directed WGRisk to set up a task group called DIGREL to initiate a new task on developing a taxonomy of failure modes of digital components for the purposes of PSA. It is an important step towards standardized digital I&C reliability assessment techniques for PSA. The objective of this paper is to provide a comparison of the failure mode taxonomies provided by the participants. The failure modes are classified in terms of their levels of detail. Software and hardware failure modes are discussed separately.

Experimentally Observed Electrical Durability of 4H-SiC JFET ICs Operating from 500 C to 700 C

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Spry, David J.; Chen, Liangyu; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2016-01-01

Prolonged 500 degrees Celsius to 700 degrees Celsius electrical testing data from 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) are combined with post-testing microscopic studies in order to gain more comprehensive understanding of the durability limits of the present version of NASA Glenn's extreme temperature microelectronics technology. The results of this study support the hypothesis that T = 500 degrees Celsius durability-limiting IC failure initiates with thermal-stress-related crack formation where dielectric passivation layers overcoat micron-scale vertical features including patterned metal traces.

Needle thoracostomy in the treatment of a tension pneumothorax in trauma patients: what size needle?

PubMed

Zengerink, Imme; Brink, Peter R; Laupland, Kevin B; Raber, Earl L; Zygun, Dave; Kortbeek, John B

2008-01-01

A tension pneumothorax requires immediate decompression using a needle thoracostomy. According to advanced trauma life support guidelines this procedure is performed in the second intercostal space (ICS) in the midclavicular line (MCL), using a 4.5-cm (2-inch) catheter (5-cm needle). Previous studies have shown a failure rate of up to 40% using this technique. Case reports have suggested that this high failure rate could be because of insufficient length of the needle. To analyze the average chest wall thickness (CWT) at the second ICS in the MCL in a trauma population and to evaluate the length of the needle used in needle thoracostomy for emergency decompression of tension pneumothoraces. Retrospective review of major trauma admissions (Injury Severity Score >12) at the Foothills Medical Centre in Calgary, Canada, who underwent a computed tomography chest scan admitted in the period from October 2001 until March 2004. Subgroup analysis on men and women, <40 years of age and >/=40 years of age was defined a priori. CWT was measured to the nearest 0.01 cm at the second ICS in the MCL. The mean CWT in the 604 male patients and 170 female patients studied averaged 3.50 cm at the left second ICS MCL and 3.51 cm on the right. The mean CWT was significantly higher for women than men (p < 0.0001). About 9.9% to 19.3% of the men had a CWT >4.5 cm and 24.1% to 35.4% of the women studied. A catheter length of 4.5 cm may not penetrate the chest wall of a substantial amount (9.9%-35.4%) of the population, depending on age and gender. This study demonstrates the need for a variable needle length for relief of a tension pneumothorax in certain population groups to improve effectiveness of needle thoracostomy.

40 CFR 63.655 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... a process shutdown shall be recorded and retained for 2 years. (ii) [Reserved] (2) The Notification... failure is detected in the control equipment. (i) For vessels for which annual inspections are required... listed in paragraphs (g)(2)(i)(A) through (g)(2)(i)(C) of this section apply. (A) A failure is defined as...

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study).

PubMed

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa; Cuenca-Estrella, Manuel

2017-09-01

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated ( P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. Copyright © 2017 Ramos et al.

Application of Microprocessor-Based Equipment in Nuclear Power Plants - Technical Basis for a Qualification Methodology

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

Korsah, K.

This document (1) summarizes the most significant findings of the ''Qualification of Advanced Instrumentation and Control (I&C) Systems'' program initiated by the Nuclear Regulatory Commission (NRC); (2) documents a comparative analysis of U.S. and European qualification standards; and (3) provides recommendations for enhancing regulatory guidance for environmental qualification of microprocessor-based safety-related systems. Safety-related I&C system upgrades of present-day nuclear power plants, as well as I&C systems of Advanced Light-Water Reactors (ALWRs), are expected to make increasing use of microprocessor-based technology. The Nuclear Regulatory Commission (NRC) recognized that the use of such technology may pose environmental qualification challenges different from current,more » analog-based I&C systems. Hence, it initiated the ''Qualification of Advanced Instrumentation and Control Systems'' program. The objectives of this confirmatory research project are to (1) identify any unique environmental-stress-related failure modes posed by digital technologies and their potential impact on the safety systems and (2) develop the technical basis for regulatory guidance using these findings. Previous findings from this study have been documented in several technical reports. This final report in the series documents a comparative analysis of two environmental qualification standards--Institute of Electrical and Electronics Engineers (IEEE) Std 323-1983 and International Electrotechnical Commission (IEC) 60780 (1998)--and provides recommendations for environmental qualification of microprocessor-based systems based on this analysis as well as on the findings documented in the previous reports. The two standards were chosen for this analysis because IEEE 323 is the standard used in the U.S. for the qualification of safety-related equipment in nuclear power plants, and IEC 60780 is its European counterpart. In addition, the IEC document was published in 1998, and should reflect any new qualification concerns, from the European perspective, with regard to the use of microprocessor-based safety systems in power plants.« less

Improving Intelligence Integration Amongst the Intelligence Community

DTIC Science & Technology

2014-06-13

numerous attacks because of the work of the men and women in the IC. Success in the IC goes unrecognized while failure becomes public knowledge...ELEMENT NUMBER 6. AUTHOR(S) Michael D. Norton, MAJ, USA 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...the process. His lifelong dedication to research and teaching enabled me the freedom to work the project knowing he was a simple call away. Dr. House

Strategy For Yield Control And Enhancement In VLSI Wafer Manufacturing

NASA Astrophysics Data System (ADS)

Neilson, B.; Rickey, D.; Bane, R. P.

1988-01-01

In most fully utilized integrated circuit (IC) production facilities, profit is very closely linked with yield. In even the most controlled manufacturing environments, defects due to foreign material are a still major contributor to yield loss. Ideally, an IC manufacturer will have ample engineering resources to address any problem that arises. In the real world, staffing limitations require that some tasks must be left undone and potential benefits left unrealized. Therefore, it is important to prioritize problems in a manner that will give the maximum benefit to the manufacturer. When offered a smorgasbord of problems to solve, most people (engineers included) will start with what is most interesting or the most comfortable to work on. By providing a system that accurately predicts the impact of a wide variety of defect types, a rational method of prioritizing engineering effort can be made. To that effect, a program was developed to determine and rank the major yield detractors in a mixed analog/digital FET manufacturing line. The two classical methods of determining yield detractors are chip failure analysis and defect monitoring on drop in test die. Both of these methods have short comings: 1) Chip failure analysis is painstaking and very time consuming. As a result, the sample size is very small. 2) Drop in test die are usually designed for device parametric analysis rather than defect analysis. To provide enough wafer real estate to do meaningful defect analysis would render the wafer worthless for production. To avoid these problems, a defect monitor was designed that provided enough area to detect defects at the same rate or better than the NMOS product die whose yield was to be optimized. The defect monitor was comprehensive and electrically testable using such equipment as the Prometrix LM25 and other digital testers. This enabled the quick accumulation of data which could be handled statistically and mapped individually. By scaling the defect densities found on the monitors to the known sensitivities of the product wafer, the defect types were ranked by defect limiting yield. (Limiting yield is the resultant product yield if there were no other failure mechanisms other than the type being considered.) These results were then compared to the product failure analysis results to verify that the monitor was finding the same types of defects in the same proportion which were troubling our product. Finally, the major defect types were isolated and reduced using the short loop capability of the monitor.

A person-centered integrated care quality framework, based on a qualitative study of patients' evaluation of care in light of chronic care ideals.

PubMed

Berntsen, Gro; Høyem, Audhild; Lettrem, Idar; Ruland, Cornelia; Rumpsfeld, Markus; Gammon, Deede

2018-06-20

Person-Centered Integrated Care (PC-IC) is believed to improve outcomes and experience for persons with multiple long-term and complex conditions. No broad consensus exists regarding how to capture the patient-experienced quality of PC-IC. Most PC-IC evaluation tools focus on care events or care in general. Building on others' and our previous work, we outlined a 4-stage goal-oriented PC-IC process ideal: 1) Personalized goal setting 2) Care planning aligned with goals 3) Care delivery according to plan, and 4) Evaluation of goal attainment. We aimed to explore, apply, refine and operationalize this quality of care framework. This paper is a qualitative evaluative review of the individual Patient Pathways (iPP) experiences of 19 strategically chosen persons with multimorbidity in light of ideals for chronic care. The iPP includes all care events, addressing the persons collected health issues, organized by time. We constructed iPPs based on the electronic health record (from general practice, nursing services, and hospital) with patient follow-up interviews. The application of the framework and its refinement were parallel processes. Both were based on analysis of salient themes in the empirical material in light of the PC-IC process ideal and progressively more informed applications of themes and questions. The informants consistently reviewed care quality by how care supported/ threatened their long-term goals. Personal goals were either implicit or identified by "What matters to you?" Informants expected care to address their long-term goals and placed responsibility for care quality and delivery at the system level. The PC-IC process framework exposed system failure in identifying long-term goals, provision of shared long-term multimorbidity care plans, monitoring of care delivery and goal evaluation. The PC-IC framework includes descriptions of ideal care, key questions and literature references for each stage of the PC-IC process. This first version of a PC-IC process framework needs further validation in other settings. Gaps in care that are invisible with event-based quality of care frameworks become apparent when evaluated by a long-term goal-driven PC-IC process framework. The framework appears meaningful to persons with multimorbidity.

Presurgical EEG-fMRI in a complex clinical case with seizure recurrence after epilepsy surgery

PubMed Central

Zhang, Jing; Liu, Qingzhu; Mei, Shanshan; Zhang, Xiaoming; Wang, Xiaofei; Liu, Weifang; Chen, Hui; Xia, Hong; Zhou, Zhen; Li, Yunlin

2013-01-01

Epilepsy surgery has improved over the last decade, but non-seizure-free outcome remains at 10%–40% in temporal lobe epilepsy (TLE) and 40%–60% in extratemporal lobe epilepsy (ETLE). This paper reports a complex multifocal case. With a normal magnetic resonance imaging (MRI) result and nonlocalizing electroencephalography (EEG) findings (bilateral TLE and ETLE, with more interictal epileptiform discharges [IEDs] in the right frontal and temporal regions), a presurgical EEG-functional MRI (fMRI) was performed before the intraoperative intracranial EEG (icEEG) monitoring (icEEG with right hemispheric coverage). Our previous EEG-fMRI analysis results (IEDs in the left hemisphere alone) were contradictory to the EEG and icEEG findings (IEDs in the right frontal and temporal regions). Thus, the EEG-fMRI data were reanalyzed with newly identified IED onsets and different fMRI model options. The reanalyzed EEG-fMRI findings were largely concordant with those of EEG and icEEG, and the failure of our previous EEG-fMRI analysis may lie in the inaccurate identification of IEDs and wrong usage of model options. The right frontal and temporal regions were resected in surgery, and dual pathology (hippocampus sclerosis and focal cortical dysplasia in the extrahippocampal region) was found. The patient became seizure-free for 3 months, but his seizures restarted after antiepileptic drugs (AEDs) were stopped. The seizures were not well controlled after resuming AEDs. Postsurgical EEGs indicated that ictal spikes in the right frontal and temporal regions reduced, while those in the left hemisphere became prominent. This case suggested that (1) EEG-fMRI is valuable in presurgical evaluation, but requires caution; and (2) the intact seizure focus in the remaining brain may cause the non-seizure-free outcome. PMID:23926432

Technical Basis for Evaluating Software-Related Common-Cause Failures

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

Muhlheim, Michael David; Wood, Richard

2016-04-01

The instrumentation and control (I&C) system architecture at a nuclear power plant (NPP) incorporates protections against common-cause failures (CCFs) through the use of diversity and defense-in-depth. Even for well-established analog-based I&C system designs, the potential for CCFs of multiple systems (or redundancies within a system) constitutes a credible threat to defeating the defense-in-depth provisions within the I&C system architectures. The integration of digital technologies into the I&C systems provides many advantages compared to the aging analog systems with respect to reliability, maintenance, operability, and cost effectiveness. However, maintaining the diversity and defense-in-depth for both the hardware and software within themore » digital system is challenging. In fact, the introduction of digital technologies may actually increase the potential for CCF vulnerabilities because of the introduction of undetected systematic faults. These systematic faults are defined as a “design fault located in a software component” and at a high level, are predominately the result of (1) errors in the requirement specification, (2) inadequate provisions to account for design limits (e.g., environmental stress), or (3) technical faults incorporated in the internal system (or architectural) design or implementation. Other technology-neutral CCF concerns include hardware design errors, equipment qualification deficiencies, installation or maintenance errors, instrument loop scaling and setpoint mistakes.« less

Dielectric Spectroscopic Detection of Early Failures in 3-D Integrated Circuits.

PubMed

Obeng, Yaw; Okoro, C A; Ahn, Jung-Joon; You, Lin; Kopanski, Joseph J

The commercial introduction of three dimensional integrated circuits (3D-ICs) has been hindered by reliability challenges, such as stress related failures, resistivity changes, and unexplained early failures. In this paper, we discuss a new RF-based metrology, based on dielectric spectroscopy, for detecting and characterizing electrically active defects in fully integrated 3D devices. These defects are traceable to the chemistry of the insolation dielectrics used in the through silicon via (TSV) construction. We show that these defects may be responsible for some of the unexplained early reliability failures observed in TSV enabled 3D devices.

Evidence of Processing Non-Idealities in 4H-SiC Integrated Circuits Fabricated with Two Levels of Metal Interconnect

NASA Technical Reports Server (NTRS)

Spry, David J.; Neudeck, Philip G.; Liangyu, Chen; Evans, Laura J.; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2015-01-01

The fabrication and prolonged 500 C electrical testing of 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) with two levels of metal interconnect is reported in another submission to this conference proceedings. While some circuits functioned more than 1000 hours at 500 C, the majority of packaged ICs from this wafer electrically failed after less than 200 hours of operation in the same test conditions. This work examines the root physical degradation and failure mechanisms believed responsible for observed large discrepancies in 500 C operating time. Evidence is presented for four distinct issues that significantly impacted 500 C IC operational yield and lifetime for this wafer.

Evidence of Processing Non-Idealities in 4H-SiC Integrated Circuits Fabricated With Two Levels of Metal Interconnect

NASA Technical Reports Server (NTRS)

Spry, David J.; Neudeck, Philip G.; Chen, Liangyu; Evans, Laura J.; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2015-01-01

The fabrication and prolonged 500 C electrical testing of 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) with two levels of metal interconnect is reported in another submission to this conference proceedings. While some circuits functioned more than 3000 hours at 500 C, the majority of packaged ICs from this wafer electrically failed after less than 200 hours of operation in the same test conditions. This work examines the root physical degradation and failure mechanisms believed responsible for observed large discrepancies in 500 C operating time. Evidence is presented for four distinct issues that significantly impacted 500 C IC operational yield and lifetime for this wafer.

Morphologic Features of the Recipient Heart in Patients Having Cardiac Transplantation and Analysis of the Congruence or Incongruence Between the Clinical and Morphologic Diagnoses

PubMed Central

Roberts, William C.; Roberts, Carey Camille; Ko, Jong Mi; Filardo, Giovanni; Capehart, John Edward; Hall, Shelley Anne

2014-01-01

Abstract Cardiac transplantation (CT) has been one of the great medical advances of the last nearly 50 years. We studied the explanted hearts of 314 patients having CT at Baylor University Medical Center Dallas from 1993 to 2012, and compared the morphologic diagnoses to the clinical diagnoses before CT. Among the 314 patients the morphologic and clinical diagnoses were congruent in 272 (87%) and incongruent in 42 (13%). Most of the incongruity occurred among the 166 patients with non-ischemic cardiomyopathy (non-IC) (36/166 [22%]), and of that group the major incongruity occurred among the patients with hypertrophic cardiomyopathy (7/17 [41%]), non-compaction left ventricular cardiomyopathy (NCLVC) (3/3 [100%]), mononuclear myocarditis (3/3 [100%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (4/4 [100%]), and cardiac sarcoidosis (8/8 [100%]). The phrase “non-IC” is a general term that includes several subsets of cardiac diseases and simply means “insignificant narrowing of 1 or more of the epicardial coronary arteries,” but it does not specify the specific cause of the heart failure leading to CT. A number of cardiac illustrations are provided to demonstrate the morphologic variability occurring among the patients with IC and non-IC. PMID:25181314

Durability Testing of Tank Track Rubber Compounds under Cyclic Loading

DTIC Science & Technology

1987-10-15

depiction of time-to-failure vs applied ( engineering ) stress for 15TP-14AX rubber compounds in creep experiments at 23"C. (After McKenna (1...behavior of the 15TP-14AX rubber was carried out at 23, 75, 125 and 175 OC. The logarithm of the time to failure vs. the applied ( engineering ) stress is...4 3I. I I 5 10 15 a/MPa Figure 3-7 Semilogarith±ic depiction of time-to--failure vs applied ( engineering ) stress for 15TP-14AX rubber compounds in

A new deletion refines the boundaries of the murine Prader–Willi syndrome imprinting center

PubMed Central

DuBose, Amanda J.; Smith, Emily Y.; Yang, Thomas P.; Johnstone, Karen A.; Resnick, James L.

2011-01-01

The human chromosomal 15q11–15q13 region is subject to both maternal and paternal genomic imprinting. Absence of paternal gene expression from this region results in Prader–Willi syndrome (PWS), while absence of maternal gene expression leads to Angelman syndrome. Transcription of paternally expressed genes in the region depends upon an imprinting center termed the PWS-IC. Imprinting defects in PWS can be caused by microdeletions and the smallest commonly deleted region indicates that the PWS-IC lies within a region of 4.3 kb. The function and location of the PWS-IC is evolutionarily conserved, but delineation of the PWS-IC in mouse has proven difficult. The first targeted mutation of the PWS-IC, a deletion of 35 kb spanning Snrpn exon 1, exhibited a complete PWS-IC deletion phenotype. Pups inheriting this mutation paternally showed a complete loss of paternal gene expression and died neonatally. A reported deletion of 4.8 kb showed only a reduction in paternal gene expression and incomplete penetrance of neonatal lethality, suggesting that some PWS-IC function had been retained. Here, we report that a 6 kb deletion spanning Snrpn exon 1 exhibits a complete PWS-IC deletion phenotype. Pups inheriting this mutation paternally lack detectable expression of all PWS genes and paternal silencing of Ube3a, exhibit maternal DNA methylation imprints at Ndn and Mkrn3 and suffer failure to thrive leading to a fully penetrant neonatal lethality. PMID:21659337

A new deletion refines the boundaries of the murine Prader-Willi syndrome imprinting center.

PubMed

Dubose, Amanda J; Smith, Emily Y; Yang, Thomas P; Johnstone, Karen A; Resnick, James L

2011-09-01

The human chromosomal 15q11-15q13 region is subject to both maternal and paternal genomic imprinting. Absence of paternal gene expression from this region results in Prader-Willi syndrome (PWS), while absence of maternal gene expression leads to Angelman syndrome. Transcription of paternally expressed genes in the region depends upon an imprinting center termed the PWS-IC. Imprinting defects in PWS can be caused by microdeletions and the smallest commonly deleted region indicates that the PWS-IC lies within a region of 4.3 kb. The function and location of the PWS-IC is evolutionarily conserved, but delineation of the PWS-IC in mouse has proven difficult. The first targeted mutation of the PWS-IC, a deletion of 35 kb spanning Snrpn exon 1, exhibited a complete PWS-IC deletion phenotype. Pups inheriting this mutation paternally showed a complete loss of paternal gene expression and died neonatally. A reported deletion of 4.8 kb showed only a reduction in paternal gene expression and incomplete penetrance of neonatal lethality, suggesting that some PWS-IC function had been retained. Here, we report that a 6 kb deletion spanning Snrpn exon 1 exhibits a complete PWS-IC deletion phenotype. Pups inheriting this mutation paternally lack detectable expression of all PWS genes and paternal silencing of Ube3a, exhibit maternal DNA methylation imprints at Ndn and Mkrn3 and suffer failure to thrive leading to a fully penetrant neonatal lethality.

The Role of a Physical Analysis Laboratory in a 300 mm IC Development and Manufacturing Centre

NASA Astrophysics Data System (ADS)

Kwakman, L. F. Tz.; Bicais-Lepinay, N.; Courtas, S.; Delille, D.; Juhel, M.; Trouiller, C.; Wyon, C.; de la Bardonnie, M.; Lorut, F.; Ross, R.

2005-09-01

To remain competitive IC manufacturers have to accelerate the development of most advanced (CMOS) technology and to deliver high yielding products with best cycle times and at a competitive pricing. With the increase of technology complexity, also the need for physical characterization support increases, however many of the existing techniques are no longer adequate to effectively support the 65-45 nm technology node developments. New and improved techniques are definitely needed to better characterize the often marginal processes, but these should not significantly impact fabrication costs or cycle time. Hence, characterization and metrology challenges in state-of-the-art IC manufacturing are both of technical and economical nature. TEM microscopy is needed for high quality, high volume analytical support but several physical and practical hurdles have to be taken. The success rate of FIB-SEM based failure analysis drops as defects often are too small to be detected and fault isolation becomes more difficult in the nano-scale device structures. To remain effective and efficient, SEM and OBIRCH techniques have to be improved or complemented with other more effective methods. Chemical analysis of novel materials and critical interfaces requires improvements in the field of e.g. SIMS, ToF-SIMS. Techniques that previously were only used sporadically, like EBSD and XRD, have become a `must' to properly support backend process development. At the bright side, thanks to major technical advances, techniques that previously were practiced at laboratory level only now can be used effectively for at-line fab metrology: Voltage Contrast based defectivity control, XPS based gate dielectric metrology and XRD based control of copper metallization processes are practical examples. In this paper capabilities and shortcomings of several techniques and corresponding equipment are presented with practical illustrations of use in our Crolles facilities.

Embedded I&C for Extreme Environments

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

Kisner, Roger A.

2016-04-01

This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pumpmore » combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.« less

Sodium-hydrogen exchanger inhibitory potential of Malus domestica, Musa × paradisiaca, Daucus carota, and Symphytum officinale.

PubMed

Verma, Vivek; Singh, Nirmal; Jaggi, Amteshwar Singh

2014-02-01

The involvement of sodium-hydrogen exchangers (NHE) has been described in the pathophysiology of diseases including ischemic heart and brain diseases, cardiomyopathy, congestive heart failure, epilepsy, dementia, and neuropathic pain. Synthetic NHE inhibitors have not achieved much clinical success; therefore, plant-derived phytoconstituents may be explored as NHE inhibitors. In the present study, the NHE inhibitory potential of hydroalcoholic and alkaloidal fractions of Malus domestica, Musa × paradisiaca, Daucus carota, and Symphytum officinale was evaluated. The different concentrations of hydroalcoholic and alkaloidal extracts of the selected plants were evaluated for their NHE inhibitory activity in the platelets using the optical swelling assay. Among the hydroalcoholic extracts, the highest NHE inhibitory activity was shown by M. domestica (IC50=2.350 ± 0.132 μg/mL) followed by Musa × paradisiaca (IC50=7.967 ± 0.451 μg/mL), D. carota (IC50=37.667 ± 2.517 μg/mL), and S. officinale (IC50=249.330 ± 1.155 μg/mL). Among the alkaloidal fractions, the highest NHE inhibitory activity was shown by the alkaloidal fraction of Musa × paradisiacal (IC50=0.010 ± 0.001 μg/mL) followed by D. carota (IC50=0.024 ± 0.002 μg/mL), M. domestica (IC50=0.031 ± 0.005 μg/mL), and S. officinale (IC50=4.233 ± 0.379 μg/mL). The IC50 of alkaloidal fractions was comparable to the IC50 of synthetic NHE inhibitor, EIPA [5-(N-ethyl-N-isopropyl)amiloride] (IC50=0.033 ± 0.004 μg/mL). It may be concluded that the alkaloidal fractions of these plants possess potent NHE inhibitory activity and may be exploited for their therapeutic potential in NHE activation-related pathological complications.

Affordable MMICs for Air Force systems

NASA Astrophysics Data System (ADS)

Kemerley, Robert T.; Fayette, Daniel F.

1991-05-01

The paper deals with a program directed at demonstrating affordable MMIC chips - the microwave/mm-wave monolithic integrated circuit (MIMIC) program. Focus is placed on experiments involving the growth and characterization of III-V materials, and the design, fabrication, and evaluation of ICs in the 1 to 60 GHz frequency range, as well as efforts related to the reliability testing, failure analysis, and generation of qualified manufacture's list procedures for GaAs MMICs and modules. Attributes associated with GaAs-technology devices, quality, reliability, and performance in select environments are discussed, including the dependence of these structures over temperature ranges, electrostatic discharge sensitivity, and susceptibility to environmental stresses.

Cost Analysis of Fluconazole Prophylaxis for Prevention of Neonatal Invasive Candidiasis.

PubMed

Swanson, Jonathan R; Vergales, Jeff; Kaufman, David A; Sinkin, Robert A

2016-05-01

Fluconazole prophylaxis (FP) in premature infants is well studied and has been shown to decrease invasive candidiasis (ICs). IC in neonates has significant financial costs; determining the cost-benefit of FP may provide additional justification for targeting high-risk neonates. We aimed to determine the IC rate in premature infants at which FP is cost-beneficial. A decision tree cost-analysis model using cost of FP related to costs associated with IC was used. We searched PubMed for all papers that used intravenous FP and reported rates of IC in very low birth weight neonates. Average IC rates in those who received FP (2.0%; range, 0-6.1%) and in those who did not receive FP (9.2%; range, 0-20.5%) were used. Incremental hospital costs because of IC and for FP were retrieved from the literature. Sensitivity analysis was performed to determine the incremental cost of FP across the range of published IC rates. The average cost per patient attributed to IC in patients receiving FP was $785 versus $2617 in those not receiving FP. Sensitivity analysis demonstrates the rate of IC would need to be <2.8% for FP to lose its cost-benefit. In Monte Carlo simulation, targeting infants <1000 g would lead to $50,304,333 in cost savings per year in the United States. FP provides a cost-advantage across most IC rates seen in the youngest premature infants. Using a rate of 2.8% for their individual high-risk neonatal intensive care unit patients, providers can determine if FP is cost-beneficial in determining for whom to provide IC prophylaxis.

Comparison of ion chromatographic methods based on conductivity detection, post-column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate.

PubMed

Schminke, G; Seubert, A

2000-02-01

An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate.

[Risk factors associated with the diagnosis of chronic Chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela].

PubMed

González, Beatriz; Silva, Martha; Al-Atrache, Yusra; Delgado, Yelitze; Serrano, José Luis; Doccimo, Angelina; Hernández, Huber; Verde, Juan; Morillo, Daniela; Marín, Jaime; Concepción, Juan Luis; Bonfante-Cabarcas, Rafael; Rodríguez-Bonfante, Claudina

2014-06-01

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI 95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC 95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC 95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC 95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Neural integration of speech and gesture in schizophrenia: evidence for differential processing of metaphoric gestures.

PubMed

Straube, Benjamin; Green, Antonia; Sass, Katharina; Kirner-Veselinovic, André; Kircher, Tilo

2013-07-01

Gestures are an important component of interpersonal communication. Especially, complex multimodal communication is assumed to be disrupted in patients with schizophrenia. In healthy subjects, differential neural integration processes for gestures in the context of concrete [iconic (IC) gestures] and abstract sentence contents [metaphoric (MP) gestures] had been demonstrated. With this study we wanted to investigate neural integration processes for both gesture types in patients with schizophrenia. During functional magnetic resonance imaging-data acquisition, 16 patients with schizophrenia (P) and a healthy control group (C) were shown videos of an actor performing IC and MP gestures and associated sentences. An isolated gesture (G) and isolated sentence condition (S) were included to separate unimodal from bimodal effects at the neural level. During IC conditions (IC > G ∩ IC > S) we found increased activity in the left posterior middle temporal gyrus (pMTG) in both groups. Whereas in the control group the left pMTG and the inferior frontal gyrus (IFG) were activated for the MP conditions (MP > G ∩ MP > S), no significant activation was found for the identical contrast in patients. The interaction of group (P/C) and gesture condition (MP/IC) revealed activation in the bilateral hippocampus, the left middle/superior temporal and IFG. Activation of the pMTG for the IC condition in both groups indicates intact neural integration of IC gestures in schizophrenia. However, failure to activate the left pMTG and IFG for MP co-verbal gestures suggests a disturbed integration of gestures embedded in an abstract sentence context. This study provides new insight into the neural integration of co-verbal gestures in patients with schizophrenia. Copyright © 2012 Wiley Periodicals, Inc.

Improving yield and reliability of FIB modifications using electrical testing

NASA Astrophysics Data System (ADS)

Desplats, Romain; Benbrik, Jamel; Benteo, Bruno; Perdu, Philippe

1998-08-01

Focused Ion Beam technology has two main areas of application for ICs: modification and preparation for technological analysis. The most solicited area is modification. This involves physically modifying a circuit by cutting lines and creating new ones in order to change the electrical function of the circuit. IC planar technologies have an increasing number of metal interconnections making FIB modifications more complex and decreasing their changes of success. The yield of FIB operations on ICs reflects a downward trend that imposes a greater number of circuits to be modified in order to successfully correct a small number of them. This requires extended duration, which is not compatible with production line turn around times. To respond to this problem, two solutions can be defined: either, reducing the duration of each FIB operation or increasing the success rate of FIB modifications. Since reducing the time depends mainly on FIB operator experience, insuring a higher success rate represents a more crucial aspect as both experienced and novice operators could benefit from this improvement. In order to insure successful modifications, it is necessary to control each step of a FIB operation. To do this, we have developed a new method using in situ electrical testing which has a direct impact on the yield of FIB modifications. We will present this innovative development through a real case study of a CMOS ASIC for high-speed communications. Monitoring the electrical behavior at each step in a FIB operation makes it possible to reduce the number of circuits to be modified and consequently reduces system costs thanks to better yield control. Knowing the internal electrical behavior also gives us indications about the impact on reliability of FIB modified circuits. Finally, this approach can be applied to failure analysis and FIB operations on flip chip circuits.

Enhanced appetitive learning and reversal learning in a mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Humby, Trevor; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2012-06-01

Prader-Willi syndrome (PWS) is caused by lack of paternally derived gene expression from the imprinted gene cluster on human chromosome 15q11-q13. PWS is characterized by severe hypotonia, a failure to thrive in infancy and, on emerging from infancy, evidence of learning disabilities and overeating behavior due to an abnormal satiety response and increased motivation by food. We have previously shown that an imprinting center deletion mouse model (PWS-IC) is quicker to acquire a preference for, and consume more of a palatable food. Here we examined how the use of this palatable food as a reinforcer influences learning in PWS-IC mice performing a simple appetitive learning task. On a nonspatial maze-based task, PWS-IC mice acquired criteria much quicker, making fewer errors during initial acquisition and also reversal learning. A manipulation where the reinforcer was devalued impaired wild-type performance but had no effect on PWS-IC mice. This suggests that increased motivation for the reinforcer in PWS-IC mice may underlie their enhanced learning. This supports previous findings in PWS patients and is the first behavioral study of an animal model of PWS in which the motivation of behavior by food rewards has been examined. © 2012 American Psychological Association

Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis.

PubMed

Ni, Songshi; Fu, Zhenxue; Zhao, Jing; Liu, Hua

2014-07-01

Studies have indicated that therapy with inhaled corticosteroids (ICS) can be associated with a higher risk of pneumonia. However, it is not known whether ICS increases the risk of mycobacterium. Most of these published studies were small, and the conclusions were inconsistent. A meta-analysis was conducted into whether ICS increases the risk of mycobacterium in patients with chronic respiratory diseases. PubMed, OVID, EMBASE and Cochrane Library databases were searched. Five studies involving 4,851 cases and 28,477 controls were considered in the meta-analysis. From the pooled analyses, there was significant association between ICS and risk of mycobacterium in all patients with chronic respiratory diseases [risk ratio (RR) =1.81; 95% confidence interval (CI), 1.23-2.68; P=0.003]. Among patients with chronic respiratory diseases, the relationship between ICS and risk of tuberculosis (TB) was also significant (RR =1.34; 95% CI, 1.15-1.55; P=0.0001). And meta-analysis of four studies in patients with chronic obstructive pulmonary disease (COPD) (RR =1.42; 95% CI, 1.18-1.72; P=0.0003) or two studies in patients who have prior pulmonary TB (RR =1.61; 95% CI, 1.35-1.92; P<0.00001) or three studies in patients with high-dose ICS (RR =1.60; 95% CI, 1.28-1.99; P<0.0001) showed a relationship between ICS and risk of mycobacterium. Significant relationship has been shown between ICS use and risk of mycobacterium in all patients with chronic respiratory diseases. ICS use also increases the risk of TB among the patients with chronic respiratory diseases. Use of ICS increases the risk of mycobacterium in patients with COPD or patients with prior pulmonary TB or patients inhaling high-dose corticosteroids. Further research is required to establish the potential adverse effect of ICS as a therapy for chronic respiratory diseases.

Low Morbidity after Extracranial-Intracranial Bypass Operation. The Danish Extracranial-Intracranial Bypass Study: A Nationwide Survey.

PubMed

von Weitzel-Mudersbach, Paul; Andersen, Grethe; Rosenbaum, Sverre

2018-06-07

Patients with symptomatic atherosclerotic carotid artery occlusion (SACAO) have a high risk of a recurrent stroke. Extracranial-intracranial bypass (EC-IC bypass) has been shown not to improve outcome compared with medical treatment alone because long-term prevention of recurrent stroke in operated patients was offset by high perioperative stroke rates. We report our experience with EC-IC bypass operated at an experienced high-volume centre. We conducted a nationwide observational study of EC-IC bypass patients operated in the years 2007-2016 due to SACAO with ongoing clinical symptoms or progression on MRI and severe haemodynamic failure (SHF). Perioperative stroke and death within 30 days after the operation, ipsilateral stroke, bypass patency, transient ischaemic attack, and all-stroke events and deaths during long-term follow-up were registered prospectively. EC-IC bypass was performed in 48 patients with SHF and SACAO. The mean age was 64 (45-83) years. The mean follow-up was 3.6 years. The stroke rate after 30 days was 4.2%. No further ipsilateral strokes occurred during follow-up. Clinical symptoms arrested in all patients. Bypass patency rate was 94%. The perioperative stroke rate in EC-IC bypass operation, performed at a highly experienced centre, was low. During long-term follow-up, no ipsilateral stroke occurred. Consequently, EC-IC-bypass should still be considered for selected patients with SACAO, if operation can be carried out in experienced centres with low perioperative morbidity. © 2018 S. Karger AG, Basel.

Nonlinear system analysis in bipolar integrated circuits

NASA Astrophysics Data System (ADS)

Fang, T. F.; Whalen, J. J.

1980-01-01

Since analog bipolar integrated circuits (IC's) have become important components in modern communication systems, the study of the Radio Frequency Interference (RFI) effects in bipolar IC amplifiers is an important subject for electromagnetic compatibility (EMC) engineering. The investigation has focused on using the nonlinear circuit analysis program (NCAP) to predict RF demodulation effects in broadband bipolar IC amplifiers. The audio frequency (AF) voltage at the IC amplifier output terminal caused by an amplitude modulated (AM) RF signal at the IC amplifier input terminal was calculated and compared to measured values. Two broadband IC amplifiers were investigated: (1) a cascode circuit using a CA3026 dual differential pair; (2) a unity gain voltage follower circuit using a micro A741 operational amplifier (op amp). Before using NCAP for RFI analysis, the model parameters for each bipolar junction transistor (BJT) in the integrated circuit were determined. Probe measurement techniques, manufacturer's data, and other researcher's data were used to obtain the required NCAP BJT model parameter values. An important contribution included in this effort is a complete set of NCAP BJT model parameters for most of the transistor types used in linear IC's.

Effectiveness and safety of imipenem/clavulanate and linezolid to treat multidrug and extensively drug-resistant tuberculosis at a referral hospital in Brazil.

PubMed

Arbex, M A; Bonini, E H; Kawakame Pirolla, G; D'Ambrosio, L; Centis, R; Migliori, G B

Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC) and linezolid containing regimens to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR) were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range) of 4.5 (2-6.5) times, having a severe resistance pattern (median number of resistances: 7 (5-8)) and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000mg/day and 600mg/day, respectively. The overall exposure was (median (IQR)) 419 (375.5-658) days for IC and 678 (392-720) days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5-90) days) and culture (75 (60-135) days), and 7 were cured while 5 are still on treatment with a gradually improving clinical picture. While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%); in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Association between lower air pressure and the onset of ischemic colitis: a case-control study.

PubMed

Kimura, Takefumi; Shinji, Akihiro; Tanaka, Naoki; Koinuma, Masayoshi; Yamaura, Maki; Nagaya, Tadanobu; Joshita, Satoru; Komatsu, Michiharu; Umemura, Takeji; Horiuchi, Akira; Wada, Shuichi; Tanaka, Eiji

2017-09-01

Ischemic colitis (IC) often affects the elderly. Proarteriosclerotic factors, such as hypertension and smoking, and cardiovascular disease are considered major contributors to IC. Although a possible link between certain cerebrocardiovascular disorders and meteorological phenomena has been reported, the relationship between IC onset and weather changes remains uninvestigated. This study examined whether specific meteorological factors were associated with the occurrence of IC. We retrospectively enrolled 303 patients who had been diagnosed with IC between January 2003 and June 2010 at Suwa Red Cross Hospital in Nagano Prefecture, Japan. The meteorological data of the days on which IC patients visited the hospital (IC+ days) were compared with those of the days on which IC patients did not (IC- days). Univariate analysis indicated that IC+ days had significantly lower air pressure (P<0.001), depressed air pressure from the previous day (P<0.001), and fewer daylight hours (P<0.001), as well as higher air temperature (P=0.017), air humidity (P=0.004), wind velocity (P<0.001), and rainfall (P=0.012) compared with IC- days. Multivariate logistic regression analysis of the meteorological data showed that air pressure (odds ratio: 0.935, P<0.001) and change in air pressure from the previous day (odds ratio: 0.934, P<0.001) were related to onset of IC. Lower air pressure and decrease in air pressure from the previous day are possible novel factors associated with the development of IC.

Evaluation of in vitro anti-Leishmanial activity of some brown, green and red algae from the Persian Gulf.

PubMed

Fouladvand, M; Barazesh, A; Farokhzad, F; Malekizadeh, H; Sartavi, K

2011-06-01

Leishmaniasis is a protozoan parasitic disease which is transmitted by the female Phlebotomus sand fly and is prevalent in four continents.The first-choice treatment for the leishmaniasis is pentavalent antimonials, which are potentially toxic and often ineffective and use of them exhibit therapeutic failure. These pharmaceutical problems point towards the need to develop novel chemotherapeutic agents. Seaweeds are considered as source of bioactive metabolites characterized by a broad spectrum of biological activities. In this experimental study, cold and hot water crude extracts of four species of green, brown and red marine algae "Caulerpa sertularioides, Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" collected along the Bushehr coast of the Persian Gulf (southwest of Iran), prepared and their in vitro activities against Leishmania major promastigote were evaluated by using the MTT assay test. The cold and hot water crude extracts of four algae species exhibited different anti-Leishmanial activities. The minimum inhibitory concentration of hot water extracts calculated as IC50 was as follows: Caulerpa sertularioides (IC50 < or =85 microg/ml), Gracilaria corticata (IC50 < or =38 microg/ml), Gracillaria salicornia (IC50 < or =46 microg/ml) and Sargassum oligocystum (IC(50)9 < or =78 microg/ml, while these values for cold water extracts were (IC50 >125 microg/ml) for Caulerpa Sertularioides (IC50 >65 microg/ml) for Gracilaria corticata (IC50 >74 microg/ml) for Gracilaria salicornia and (IC50 >105 microg/ml) for Sargassum oligocystum, IC50 values for reference drug (Amphotericin B) was (0.16-0.2 microg/ml). According to the results, inhibitory effects of the crude extracts from these four species algae specially hot water crude extracts from "Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" are significant and in accordance with other studies that has been done on different algae species. So these results are sufficiently promising to be followed with further studies on isolation and characterization of pure compounds from these algae species as well as in vivo experiments, a work that is already under way in our laboratory.

Endothelin-1 inactivating peptidase in the human kidney and urine.

PubMed

Janas, J; Sitkiewicz, D; Januszewicz, A; Szczesniak, C; Grenda, R; Janas, R M

2000-04-01

Recently, an apparently novel, specific endothelin-1 inactivating metalloendopeptidase (ET-1 peptidase) has been isolated from the rat kidney. In this study we attempted to determine whether the same or a similar peptidase is present in the human kidney, and whether the enzyme is excreted into the urine. The urinary ET-1 peptidase could serve as an indirect index of the renal endothelin system, both in physiology and pathophysiology. Kidney specimens were obtained from part of nephrectomized kidneys unaffected by any neoplastic process from six adult patients. The enzyme was purified using differential centrifugation, detergent solubilization of the membrane proteins, ultrafiltration and nondenaturing gel electrophoresis. The enzyme activity assays were performed at pH 5.5 and 37 degrees C in the presence of increasing concentrations of unlabelled peptides and inhibitors using a fixed amount of [125I]ET-1 as substrate. The degradation extent was quantified with trichloroacetic acid precipitation and high performance liquid chromatography. The degrading activity of ET-1 was determined in urine samples from adult patients with hypertension, children with chronic renal failure and those with stable renal allograft ET-1 peptidase from the human kidney displays characteristics close to that of the rat ET-1 peptidase we have recently described (J. Hypertens 1994; 12:1155-1162). The enzyme, a membrane-bound metalloendopeptidase, exhibits low electro- phoretical mobility on nondenaturing gel (Rf 0.08); it is an apparently heterologous structure comprising three enzymatically inactive subunits, it has a pH optimum at 5.5, a nanomolar range affinity to the ET-1 (KM 180 nmol/l) that is hydrolysed to two main degradation products, and a 10-100-fold lower affinity to big ET-1 (KM 11.5 micromol/l), endothelin 11 21 fragment (KM 15.3 micromol/l), endothelin antagonist Trp-Leu-Asp-Ile-Ile-Trp (KM 3.1 micromol/I), gastrin (KM 2.2 micromol/l) and cholecystokinin (KM 4.0 micromol/l). Substance P, neuropeptide Y, atrial natriuretic peptide, bradykinin, angiotensin II and enkephalin were poor substrates for the enzyme. The most powerful inhibitors of the ET-1 peptidase included thiorphan (IC50 0.28 nmol/l), phosphoramidon (IC50 0.55 nmol/l), phenanthroline (IC50 11.5 micromol/l), cyclosporin (IC50 400 micromol/l), phosphate (IC50 1.2 mmol/l), citrate (IC50 0.6 mmol/l) and aniline naphthalene sulphonic acid (IC50 0.25 mmol/l). Our data suggest that three ET-1 degrading peptidases with optimal activity at pH 4.5, 5.5 and 7.0, respectively, are excreted into the urine. The enzyme with a pH optimum 4.5 is of lysosomal origin whereas the two other enzymes correspond by their pH optima to the renal ET-1 peptidase and neutral endopeptidase. We have found statistically significant increases (P < 0.001) in the activity of both lysosomal and ET-1 peptidase in the urine in patients with hypertension and in children with chronic renal failure compared with healthy subjects or children with stable renal allograft Human kidney contains an acidic, highly specific endothelin-1 inactivating metalloendopeptidase that may have a key role in the regulation of concentrations of renal and circulating endothelins. The enzyme is excreted into the urine where its activity seems to be increased in patients with hypertension and chronic renal failure; it may potentially serve as an indirect index of the renal endothelin system.

Stool-based biomarkers of interstitial cystitis/bladder pain syndrome.

PubMed

Braundmeier-Fleming, A; Russell, Nathan T; Yang, Wenbin; Nas, Megan Y; Yaggie, Ryan E; Berry, Matthew; Bachrach, Laurie; Flury, Sarah C; Marko, Darlene S; Bushell, Colleen B; Welge, Michael E; White, Bryan A; Schaeffer, Anthony J; Klumpp, David J

2016-05-18

Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.

Developing a core outcome set for infant colic for primary, secondary and tertiary care settings: a prospective study.

PubMed

Steutel, Nina F; Benninga, Marc A; Langendam, Miranda W; Korterink, Judith J; Indrio, Flavia; Szajewska, Hania; Tabbers, Merit M

2017-05-29

Infant colic (IC) is defined as recurrent and prolonged crying without an obvious cause or evidence of failure to thrive or illness. It is a common problem with a prevalence of 5%-25%. The unknown aetiology results in a wide variety in interventions and use of heterogeneous outcome measures across therapeutic trials. Our aim was to develop a core outcome set (COS) for IC to facilitate and improve evidence synthesis. Prospective study design; primary, secondary and tertiary care. The COS was developed using a modified Delphi technique. First, healthcare professionals (HCPs) and parents of infants with IC were asked to list up to five outcomes they considered relevant in the treatment of IC. Outcomes mentioned by >10% of participants were forwarded to a shortlist. In the second round, outcomes on this shortlist were rated and prioritised. The final COS was defined in a face-to-face expert meeting of paediatricians. F of invited stakeholders (133 HCPs and 55 parents of infants with IC) completed both Delphi rounds. Duration of crying, family stress, sleeping time of infant, quality of life (of family), discomfort of infant and hospital admission/duration were rated as most important outcomes in IC, framing the final COS. The use of this COS should serve as a minimum of outcomes to be measured and reported. This will benefit evidence synthesis, by enhancing homogeneity of outcomes, and enable evaluation of success in therapeutic trials on IC. Researchers are strongly encouraged to use this COS when setting up a clinical trial in primary, secondary and/or tertiary care or performing a systematic review on IC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lateral and posterior dynamic bending of the mid-shaft femur: fracture risk curves for the adult population.

PubMed

Kennedy, Eric A; Hurst, William J; Stitzel, Joel D; Cormier, Joseph M; Hansen, Gail A; Smith, Eric P; Duma, Stefan M

2004-11-01

The purpose of this study was to develop injury risk functions for dynamic bending of the human femur in the lateral-to-medial and posterior-to-anterior loading directions. A total of 45 experiments were performed on human cadaver femurs using a dynamic three-point drop test setup. An impactor of 9.8 kg was dropped from 2.2 m for an impact velocity of 5 m/s. Five-axis load cells measured the impactor and support loads, while an in situ strain gage measured the failure strain and subsequent strain rate. All 45 tests resulted in mid-shaft femur fractures with comminuted wedge and oblique fractures as the most common fracture patterns. In the lateral-to-medial bending tests the reaction loads were 4180 +/- 764 N, and the impactor loads were 4780 +/- 792 N. In the posterior-to-anterior bending tests the reaction loads were 3780 +/- 930 N, and the impactor loads were 4310 +/- 1040 N. The difference between the sum of the reaction forces and the applied load is due to inertial effects. The reaction loads were used to estimate the mid-shaft bending moments at failure since there was insufficient data to include the inertial effects in the calculations. The resulting moments are conservative estimates (lower bounds) of the mid-shaft bending moments at failure and are appropriate for use in the assessment of knee restraints and pedestrian impacts with ATD measurements. Regression analysis was used to identify significant parameters, and parametric survival analysis was used to estimate risk functions. Femur cross-sectional area, area moment of inertia (I), maximum distance to the neutral axis (c), I/c, occupant gender, and occupant mass are shown to be significant predictors of fracture tolerance, while no significant difference is shown for loading direction, bone mineral density, leg aspect and age. Risk functions are presented for femur cross-sectional area and I/c as they offer the highest correlation to peak bending moment. The risk function that utilizes the most highly correlated (R2 = 0.82) and significant (p = 0.0001) variable, cross-sectional area, predicts a 50 percent risk of femur fracture of 240 Nm, 395 Nm, and 562 Nm for equivalent cross-sectional area of the 5(th) percentile female, 50(th) percentile male, and 95(th) percentile male respectively.

Adaptive kernel independent component analysis and UV spectrometry applied to characterize the procedure for processing prepared rhubarb roots.

PubMed

Wang, Guoqing; Hou, Zhenyu; Peng, Yang; Wang, Yanjun; Sun, Xiaoli; Sun, Yu-an

2011-11-07

By determination of the number of absorptive chemical components (ACCs) in mixtures using median absolute deviation (MAD) analysis and extraction of spectral profiles of ACCs using kernel independent component analysis (KICA), an adaptive KICA (AKICA) algorithm was proposed. The proposed AKICA algorithm was used to characterize the procedure for processing prepared rhubarb roots by resolution of the measured mixed raw UV spectra of the rhubarb samples that were collected at different steaming intervals. The results show that the spectral features of ACCs in the mixtures can be directly estimated without chemical and physical pre-separation and other prior information. The estimated three independent components (ICs) represent different chemical components in the mixtures, which are mainly polysaccharides (IC1), tannin (IC2), and anthraquinone glycosides (IC3). The variations of the relative concentrations of the ICs can account for the chemical and physical changes during the processing procedure: IC1 increases significantly before the first 5 h, and is nearly invariant after 6 h; IC2 has no significant changes or is slightly decreased during the processing procedure; IC3 decreases significantly before the first 5 h and decreases slightly after 6 h. The changes of IC1 can explain why the colour became black and darkened during the processing procedure, and the changes of IC3 can explain why the processing procedure can reduce the bitter and dry taste of the rhubarb roots. The endpoint of the processing procedure can be determined as 5-6 h, when the increasing or decreasing trends of the estimated ICs are insignificant. The AKICA-UV method provides an alternative approach for the characterization of the processing procedure of rhubarb roots preparation, and provides a novel way for determination of the endpoint of the traditional Chinese medicine (TCM) processing procedure by inspection of the change trends of the ICs.

Iodine concentration: a new, important characteristic of the spot sign that predicts haematoma expansion.

PubMed

Fu, Fan; Sun, Shengjun; Liu, Liping; Li, Jianying; Su, Yaping; Li, Yingying

2018-04-19

The computed tomography angiography (CTA) spot sign is a validated predictor of haematoma expansion (HE) in spontaneous intracerebral haemorrhage (SICH). We investigated whether defining the iodine concentration (IC) inside the spot sign and the haematoma on Gemstone spectral imaging (GSI) would improve its sensitivity and specificity for predicting HE. From 2014 to 2016, we prospectively enrolled 65 SICH patients who underwent single-phase spectral CTA within 6 h. Logistic regression was performed to assess the risk factors for HE. The predictive performance of individual spot sign characteristics was examined via receiver operating characteristic (ROC) analysis. The spot sign was detected in 46.1% (30/65) of patients. ROC analysis indicated that IC inside the spot sign had the greatest area under the ROC curve for HE (0.858; 95% confidence interval, 0.727-0.989; p = 0.003). Multivariate analysis found that spot sign with higher IC (i.e. IC > 7.82 100 μg/ml) was an independent predictor of HE (odds ratio = 34.27; 95% confidence interval, 5.608-209.41; p < 0.001) with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.81, 0.75, 0.90 and 0.60, respectively; while the spot sign showed sensitivity, specificity, PPV and NPV of 0.81, 0.79, 0.73 and 0.86. Logistic regression analysis indicated that the IC in haematomas was independently associated with HE (odds ratio = 1.525; 95% confidence interval, 1.041-2.235; p = 0.030). ICs in haematoma and in spot sign were all independently associated with HE. IC analysis in spectral imaging may help to identify SICH patients for targeted haemostatic therapy. • Iodine concentration in spot sign and haematoma can predict haematoma expansion • Spectral imaging could measure the IC inside the spot sign and haematoma • IC in spot sign improved the positive predictive value (PPV) cf. CTA.

Long-term outcomes of intravesical dimethyl sulfoxide/heparin/hydrocortisone therapy for interstitial cystitis/bladder pain syndrome.

PubMed

Lim, Yik N; Dwyer, Peter; Murray, Christine; Karmakar, Debjyoti; Rosamilia, Anna; Thomas, Elizabeth

2017-07-01

For decades, intravesical dimethyl sulfoxide (DMSO) cocktail therapy has been used for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), but little is known about its long-term efficacy. We aimed to assess the long-term efficacy of intravesical DMSO/heparin/hydrocortisone/bupivacaine therapy in patients with IC/BPS. Patients with IC/BPS from our institutions who underwent this therapy with >2 years follow-up were surveyed with O'Leary-Sant interstitial cystitis symptom and problem index questionnaires before and after therapy. Chart reviews and telephone surveys were then conducted to determine their posttherapy course. Of 68 eligible women, 55 (80.0%) with a median follow-up of 60 months (range 24-142) were surveyed. Their mean age at therapy onset was 44.8 years and their mean body mass index was 26.2 kg/m 2 . There were statistically significant improvements in O'Leary-Sant and pain scores of 23-47% at both 6 weeks and the end of the follow-up period. At the end of the follow-up period, 19 of the 55 women (34.5%) were cured (requiring no further treatment) and 12 (21.8%) were significantly improved (requiring only ongoing oral medication). Univariate and multivariate analyses showed that DMSO treatment failure was more likely in patients with pretreatment day-time urinary frequency more than 15 episodes per day (OR 1.41), nocturia more than two episodes per night (OR 2.47), maximum bladder diary voided volume <200 ml (OR 1.39) and bladder capacity under anaesthesia <500 ml (OR 1.6). At a median follow-up of 60 months, intravesical DMSO cocktail therapy appeared moderately effective for the treatment of IC/BPS. Treatment failure was more frequent in patients with pretreatment symptoms of reduced bladder capacity.

Partner-Drug Resistance and Population Substructuring of Artemisinin-Resistant Plasmodium falciparum in Cambodia

PubMed Central

Parobek, Christian M.; Parr, Jonathan B.; Brazeau, Nicholas F.; Lon, Chanthap; Chaorattanakawee, Suwanna; Gosi, Panita; Barnett, Eric J.; Norris, Lauren D.; Meshnick, Steven R.; Spring, Michele D.; Lanteri, Charlotte A.; Bailey, Jeffrey A.; Saunders, David L.; Lin, Jessica T.

2017-01-01

Abstract Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region. One cluster displayed ex vivo piperaquine resistance and mefloquine sensitivity with a high rate of in vivo failure of dihydroartemisinin-piperaquine. Another cluster displayed ex vivo mefloquine resistance and piperaquine sensitivity with high in vivo efficacy of dihydroartemisinin-piperaquine. The final cluster was clonal and displayed intermediate sensitivity to both drugs. Variations in recently described piperaquine resistance markers did not explain the difference in mean IC90 or clinical failures between the high and intermediate piperaquine resistance groups, suggesting additional loci may be involved in resistance. The results highlight an important role for partner drug resistance in shaping the P. falciparum genetic landscape in Southeast Asia and suggest that further work is needed to evaluate for other mutations that drive piperaquine resistance. PMID:28854635

Methods for therapeutic trials in COPD: lessons from the TORCH trial.

PubMed

Keene, O N; Vestbo, J; Anderson, J A; Calverley, P M A; Celli, B; Ferguson, G T; Jenkins, C; Jones, P W

2009-11-01

The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation. When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments. The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study. Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.

New limits on intrinsic charm in the nucleon from global analysis of parton distributions

DOE PAGES

Jimenez-Delgado, P.; Hobbs, T. J.; Londergan, J. T.; ...

2015-02-27

We present a new global QCD analysis of parton distribution functions, allowing for possible intrinsic charm (IC) contributions in the nucleon inspired by light-front models. The analysis makes use of the full range of available high-energy scattering data for Q 2 ≥ 1 GeV 2 and W 2 ≥ 3.5 GeV 2, including fixed-target proton and deuteron deep cross sections at lower energies that were excluded in previously global analyses. The expanded data set places more stringent constraints on the momentum carried by IC, with (x) IC at most 0.5% (corresponding to an IC normalization of ~1%) at the 4σmore » level for Δ X2 = 1. We also assess the impact of older EMC measurements of F c 2c at large x, which favor a nonzero IC, but with very large X 2 values.« less

Integrated Circuit Wear out Prediction and Recycling Detection using Radio Frequency Distinct Native Attribute Features

DTIC Science & Technology

2016-12-22

105 A.1 Main Loop ... loop monitoring for preventative maintenance rather than early replacement based on statistical projections or replacement-after- failure schemes. IC...estimates, RF-DNA may provide a means to track an IC’s physical degradation during actual use. Monitoring an IC’s degradation in a closed loop fashion

Identifying barriers to patient acceptance of active surveillance: content analysis of online patient communications.

PubMed

Mishra, Mark V; Bennett, Michele; Vincent, Armon; Lee, Olivia T; Lallas, Costas D; Trabulsi, Edouard J; Gomella, Leonard G; Dicker, Adam P; Showalter, Timothy N

2013-01-01

Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS. English-language ICs regarding prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC)-(#Negative IC/#Total IC) x 100]. A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

Determination of the chest wall thicknesses and needle thoracostomy success rates at second and fifth intercostal spaces: a cadaver-based study.

PubMed

Ozen, Can; Akoglu, Haldun; Ozdemirel, Rifat Ozgur; Omeroglu, Elif; Ozpolat, Cigdem Ulubay; Onur, Ozge; Buyuk, Yalcin; Denizbasi, Arzu

2016-12-01

The purposes of this study were to measure the chest wall thicknesses (CWTs) at second intercostal space (ICS) mid-clavicular line (MCL) and fifth ICS MAL directly, and compare the actual success rates of needle thoracostomies (NTs) by inserting a 5-cm-long syringe needle. Predictive values of weight, body mass index (BMI) and CWT were also analyzed. This study included 199 measurements of 50 adult fresh cadavers from both hemithoraces. Five-centimeter-long syringe needles were inserted and secured. Penetration into the pleural cavity was assessed, and CWTs at 4 locations were measured. Achieved power of this study for the primary aim of CWT comparison from 2 nd and 5 th ICSs was .94. Overall mean CWTs at 2 nd ICS MCL and 5 th ICS MAL were measured as 2.46 ± 0.78 and 2.89 ± 1.09, respectively, and 5 th ICS MAL was found to be statistically thicker (P = .002). The success rate of NT at 2 nd ICS MCL was 87% (95% CI, 80-94), and that at 5 th ICS MAL was 78% (95% CI, 70-86; P = .3570). Only 6 (17.1%) of 35 failed NTs had a CWT greater than 5-cm. Needle thoracostomy has failed in 29 (14.9%) of 194 locations, despite a CWT less than 5-cm. Below a weight of 72 kg, BMI of 23 kg/m 2 , or CWT of 2.4 cm, all NTs were successful. In this report, we present the largest cadaver-based cohort to date to the best of our knowledge, and we observed a statistically nonsignificant 9% more NT success rate at 2 nd ICS at a power of 88% and statistically significant more success rate in males at 5 th ICS was (47.7%). We also observed thinner CWTs and higher success rates than previous imaging-based studies. A BMI of 23 kg/m 2 or less and weight of 72 kg or less seem to accurately rule-out NT failure in cadavers, and they seem to be better predictors at the bedside. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy.

PubMed

Bajraktari, Gani; Miccoli, Mario; Buralli, Simona; Fontanive, Paolo; Elezi, Shpend; Metelli, Maria Rita; Baggiani, Angelo; Dini, Frank Lloyd

2012-10-01

Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients. Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction ≤ 40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150 ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25 ± 17 months. Median value of MMP-9 was 714 ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5 ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure ≥ 35 mm Hg, N-terminal protype-B natriuretic peptide>1742 pg/ml, and glomerular filtration rate<60 ml/min/1.73 m(2). Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan-Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001). MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients. Copyright © 2012. Published by Elsevier B.V.

Differentiating malignant from benign gastric mucosal lesions with quantitative analysis in dual energy spectral computed tomography: Initial experience.

PubMed

Meng, Xiaoyan; Ni, Cheng; Shen, Yaqi; Hu, Xuemei; Chen, Xiao; Li, Zhen; Hu, Daoyu

2017-01-01

To investigate the value of quantitative analysis in dual energy spectral computed tomography (DESCT) for differentiating malignant gastric mucosal lesions from benign gastric mucosal lesions (including gastric inflammation [GI] and normal gastric mucosa [NGM]). This study was approved by the ethics committee, and all patients provided written informed consent. A total of 161 consecutive patients (63 with gastric cancer [GC], 48 with GI, and 50 with NGM) who underwent dual-phase contrast enhanced DESCT scans in the arterial phase (AP) and portal venous phase (PVP) were included in this study. Iodine concentration (IC) in lesions was derived from the iodine-based material-decomposition images and normalized to that in the aorta to obtain normalized IC (nIC). The ratios of IC and nIC between the AP and PVP were calculated. Diagnostic confidence for GC and GI was evaluated with reviewing the features including gastric wall thickness, focal, and eccentric on the conventional polychromatic images. All statistical analyses were performed by using statistical software SPSS 17.0 (SPSS, Chicago, IL). IC and nIC in GC differed significantly from those in GI and NGM, except for nICAP in comparing GC with GI. Mean nIC values of GC (0.18 ± 0.06 in AP and 0.62 ± 0.16 in PVP) were significantly higher than that of NGM (0.12 ± 0.03 in AP and 0.37 ± 0.08 in PVP) (all P < 0.05). There was also significant difference for IC values in GC, GI, and NGM (24.19 ± 8.27, 19.07 ± 5.82, and 13.61 ± 2.52 mg/mL, respectively, in AP and 28.00 ± 7.01, 24.66 ± 6.55, and 16.94 ± 3.06 mg/mL, respectively, in PVP). Based on Receiver Operating Characteristic Curve analysis, nIC and IC in PVP had high sensitivities of 88.89% and 90.48%, respectively, in differentiating GC from NGM, while the sensitivities were 71.43% and 88.89% during AP. Ratios IC and nIC ratios did not provide adequate diagnostic accuracy with their area under curves less than 0.65. With the conventional features, the diagnostic accuracies for GC and GI were 75.0% and 98.0%, respectively. Quantitative analysis of DESCT imaging parameters for gastric mucosa, such as nIC and IC, is useful for differentiating malignant from benign gastric mucosal lesions.

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

Prolonged 500 C Operation of 100+ Transistor Silicon Carbide Integrated Circuits

NASA Technical Reports Server (NTRS)

Spry, David J.; Neudeck, Philip G.; Lukco, Dorothy; Chen, Liangyu; Krasowski, Michael J.; Prokop, Norman F.; Chang, Carl W.; Beheim, Glenn M.

2017-01-01

This report describes more than 5000 hours of successful 500 C operation of semiconductor integrated circuits (ICs) with more than 100 transistors. Multiple packaged chips with two different 4H-SiC junction field effect transistor (JFET) technology demonstrator circuits have surpassed thousands of hours of oven-testing at 500 C. After 100 hours of 500 C burn-in, the circuits (except for 2 failures) exhibit less than 10% change in output characteristics for the remainder of 500 C testing. We also describe the observation of important differences in IC materials durability when subjected to the first nine constituents of Venus-surface atmosphere at 9.4 MPa and 460 C in comparison to what is observed for Earth-atmosphere oven testing at 500 C.

Prolonged 500 C Operation of 100+ Transistor Silicon Carbide Integrated Circuits

NASA Technical Reports Server (NTRS)

Spry, David J.; Neudeck, Philip G.; Lukco, Dorothy; Chen, Liangyu; Krasowski, Michael J.; Prokop, Norman F.; Chang, Carl W.; Beheim, Glenn M.

2017-01-01

This report describes more than 5000 hours of successful 500 C operation of semiconductor integrated circuits (ICs) with more than 100 transistors. Multiple packaged chips with two different 4H-SiC junction field effect transistor (JFET) technology demonstrator circuits have surpassed thousands of hours of oven-testing at 500 C. After 100 hours of 500 C burn-in, the circuits (except for 2 failures) exhibit less than 10 change in output characteristics for the remainder of 500C testing. We also describe the observation of important differences in IC materials durability when subjected to the first nine constituents of Venus-surface atmosphere at 9.4 MPa and 460C in comparison to what is observed for Earth-atmosphere oven testing at 500 C.

Informed consent: a socio-legal study.

PubMed

Rathor, M Y; Rani, Mohammad Fauzi Abdul; Shah, Azarisman Mohammad; Akter, Sheikh Fariuddin

2011-12-01

Informed consent [IC] is a recognized socio-legal obligation for the medical profession. The doctrine of IC involves the law, which aims to ensure the lawfulness of health assistance and tends to reflect the concept of autonomy of the person requiring and requesting medical and/or surgical treatment. Recent changes in the health care delivery system and the complex sociological settings, in which it is practiced, have resulted in an increase in judicial activity and medical negligence lawsuits for physicians. While IC is a well-established practice, it often fails to meet its stated purpose. In the common law, the standard of medical care to disclose risks has been laid down by the Bolam test- a familiar concept to most physicians, but it has been challenged recently in many jurisdictions. This paper aims to discuss some important judgments in cases of alleged medical negligence so as to familiarize doctors regarding their socio-legal obligations. We also propose to discuss some factors that influence the quality of IC in clinical practice. Literature review. The law of medical consent has been undergoing changes in recent years. Case law appears to be evolving towards a more patient centered standard of disclosure. Patient's expectations are higher and they are aware of the power of exercising their rights. Failure to obtain IC is one of the common allegations in medical malpractice suits. The medical professionals need to change their mindset and avoid claims of negligence by providing information that is "reasonable" in the eyes of the court.

Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

PubMed

Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

2011-12-01

To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc. All rights reserved.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

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

Sher, David J., E-mail: dsher@partners.org; Posner, Marshall R.; Tishler, Roy B.

2011-12-01

Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8more » weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.« less

Bus current analysis of high power cryocooler's controller

NASA Astrophysics Data System (ADS)

Jin, Zhanlei; Sun, Qiyang; Dai, Liqun; Dong, Jie

2016-03-01

Current analysis was an important research content for reducing power of cryocooler's controller. Simulation was done among load current, H bridge current and power current refer to 42V bus power voltage. Then relationship among IL1, IC1, ρ and IM1 was established. Simulation results indicate that IL1-max, IL1-ave, IL1-rms, IC1-min and IC1-ave were linearly increasing to ρ and IM1, especially IL1-rms ≈ 0.612ρ IM1-max . IC1-rms increase firstly then decrease with the increasing of ρ. IC1-rms reaches maximum when ρ=0.8, then ICL-rms =(12.32/RM1 + 0.98) exp -((ρ-0.78)/0.57)2. The results were useful for miniaturizing cryocooler's controller.

Cobra venom cytotoxins; apoptotic or necrotic agents?

PubMed

Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

2015-12-15

Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reliability Assessment of Critical Electronic Components

DTIC Science & Technology

1992-07-01

Failures FLHP - Full Horse Power FSN - Federal Stock Number I Current IC - Integrated Circuit IPB - Illustrated Parts Breakdown K - Boltzmans Constant L...Classified P - Power PC - Printed Circuit PCB - Printed Circuit Board PGA - Pin Grid Array PPM - Parts Per Million PWB - Printed Wiring Board 0...4-59 4.4.3.2.3 Circuit Brcakers ......................................................... 4-59 4.4.3.2.4 Thermal

Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis.

PubMed

Hertel, Nadine; Kotchie, Robert W; Samyshkin, Yevgeniy; Radford, Matthew; Humphreys, Samantha; Jameson, Kevin

2012-01-01

Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD), despite the availability of several treatment options. This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting. A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta agonist (LABA), an inhaled corticosteroid (ICS), and roflumilast in a fully incremental analysis. Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately. Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison. The analysis was conducted from the UK National Health Service (NHS) perspective. Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis. Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources. For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment. Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained). The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13,764/QALY gained. The relative rate ratio of exacerbations was identified as the primary driver of cost-effectiveness. The treatment algorithm recommended in UK clinical practice represents a cost-effective approach for the management of COPD. The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy.

Changes in hydrological connectivity due to vegetation recovery and wall collapse in abandoned terraced fields

NASA Astrophysics Data System (ADS)

Lana-Renault, Noemí; López-Vicente, Manuel; Oranjuren, Rafael; Ángel Llorente, José; Ruiz-Flaño, Purificación; Arnáez, José

2017-04-01

Agricultural terraces have been built in mountain regions worldwide in order to provide a larger surface for cultivation, improve water availability and reduce soil erosion, as they favour infiltration and reduce runoff and sediment connectivity from hillslopes to streams. In many Mediterranean countries, farmland abandonment has led to progressive natural revegetation and, in terraced slopes, due to a lack of maintenance, to a collapse of the water conservation structures, often followed by small mass movements and gullying. Little is known about the effect of such failures on the hydrological system, especially at catchment scale. The aim of this study is to contributing to fill in this gap by exploring the effect of vegetation recovery and terrace failure on hydrological connectivity in a small catchment (192 ha) in northern Spain mostly occupied by abandoned terraced fields. For this purpose, we applied a modified version of the Borselli's index of runoff and sediment connectivity (IC). Besides using the C-RUSLE factor, as used by many authors, we tested the inclusion of an infiltration component (Kf) to assess the landscape-weighting factor. The Kf factor accounted for the high infiltration rates observed in the terraced soils and was estimated using the permeability classes of the K-RUSLE factor. A 2x2 m resolution DEM was used to capture the terraced fields and run the IC model. Following the recommendation of Cavalli et al. (2015), we used the D-infinity flow accumulation algorithm (Tarboton, 1997) to represent the real flow paths, especially on hillslopes, where divergent flow predominates, and on stream channels. To ensure the continuity of the flow path lines, local sinks were filled in with the algorithm of Planchon & Darboux (2001) that preserved a minimum slope gradient of 0.01 degrees. Finally, linear landscape elements such as stonewalls, rock outcrops, and trails and forest roads were also considered. The IC was calculated for the current scenario and the results were validated in the field by identifying stable, erosion, delivery and sedimentation forms in a representative sub-catchment. We then applied the IC for the past scenario, when all terraced fields were cultivated, and we analysed the changes in connectivity due to farmland abandonment, including the separate effect of changes in vegetation, linear landscape elements and water conservation structures. Results of this study have implications for other agro-ecosystems sensitive to farmland abandonment as well as where terrace failure may happen.

Picosecond imaging of signal propagation in integrated circuits

NASA Astrophysics Data System (ADS)

Frohmann, Sven; Dietz, Enrico; Dittrich, Helmar; Hübers, Heinz-Wilhelm

2017-04-01

Optical analysis of integrated circuits (IC) is a powerful tool for analyzing security functions that are implemented in an IC. We present a photon emission microscope for picosecond imaging of hot carrier luminescence in ICs in the near-infrared spectral range from 900 to 1700 nm. It allows for a semi-invasive signal tracking in fully operational ICs on the gate or transistor level with a timing precision of approximately 6 ps. The capabilities of the microscope are demonstrated by imaging the operation of two ICs made by 180 and 60 nm process technology.

Study of complete interconnect reliability for a GaAs MMIC power amplifier

NASA Astrophysics Data System (ADS)

Lin, Qian; Wu, Haifeng; Chen, Shan-ji; Jia, Guoqing; Jiang, Wei; Chen, Chao

2018-05-01

By combining the finite element analysis (FEA) and artificial neural network (ANN) technique, the complete prediction of interconnect reliability for a monolithic microwave integrated circuit (MMIC) power amplifier (PA) at the both of direct current (DC) and alternating current (AC) operation conditions is achieved effectively in this article. As a example, a MMIC PA is modelled to study the electromigration failure of interconnect. This is the first time to study the interconnect reliability for an MMIC PA at the conditions of DC and AC operation simultaneously. By training the data from FEA, a high accuracy ANN model for PA reliability is constructed. Then, basing on the reliability database which is obtained from the ANN model, it can give important guidance for improving the reliability design for IC.

Application of Receiver Operating Characteristic Analysis to Refine the Prediction of Potential Digoxin Drug Interactions

PubMed Central

Ellens, Harma; Deng, Shibing; Coleman, JoAnn; Bentz, Joe; Taub, Mitchell E.; Ragueneau-Majlessi, Isabelle; Chung, Sophie P.; Herédi-Szabó, Krisztina; Neuhoff, Sibylle; Palm, Johan; Balimane, Praveen; Zhang, Lei; Jamei, Masoud; Hanna, Imad; O’Connor, Michael; Bednarczyk, Dallas; Forsgard, Malin; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hillgren, Kathleen M.; Li, LiBin; Pak, Anne Y.; Perloff, Elke S.; Rajaraman, Ganesh; Salphati, Laurent; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yamagata, Tetsuo

2013-01-01

In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ≥0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml divide by IC50 ([I2]/IC50) is ≥10. In this article, refined criteria are presented, determined by receiver operating characteristic analysis, using IC50 values generated by 23 laboratories. P-gp probe substrates were digoxin for polarized cell-lines and N-methyl quinidine or vinblastine for P-gp overexpressed vesicles. Inhibition of probe substrate transport was evaluated using 15 known P-gp inhibitors. Importantly, the criteria derived in this article take into account variability in IC50 values. Moreover, they are statistically derived based on the highest degree of accuracy in predicting true positive and true negative digoxin DDI results. The refined criteria of [I1]/IC50 ≥ 0.03 and [I2]/IC50 ≥ 45 and FDA criteria were applied to a test set of 101 in vitro-in vivo digoxin DDI pairs collated from the literature. The number of false negatives (none predicted but DDI observed) were similar, 10 and 12%, whereas the number of false positives (DDI predicted but not observed) substantially decreased from 51 to 40%, relative to the FDA criteria. On the basis of estimated overall variability in IC50 values, a theoretical 95% confidence interval calculation was developed for single laboratory IC50 values, translating into a range of [I1]/IC50 and [I2]/IC50 values. The extent by which this range falls above the criteria is a measure of risk associated with the decision, attributable to variability in IC50 values. PMID:23620486

Inhaled corticosteroids and the occurrence of oral candidiasis: a prescription sequence symmetry analysis.

PubMed

van Boven, Job F M; de Jong-van den Berg, Lolkje T W; Vegter, Stefan

2013-04-01

The primary aim of the study was to gain insight into the relative risk of clinically relevant oral candidiasis following inhaled corticosteroid (ICS) initiation over time. A secondary aim was to analyse the influence of patient characteristics and co-medication on the occurrence of this adverse effect. Drug prescription data from 1994 to 2011 were retrieved from the IADB.nl database. To study the influence of ICS use on occurrence of oral candidiasis, a prescription symmetry analysis was used, including patients using medication for oral candidiasis up to 1 year before or after ICS initiation. The relative risk was calculated by dividing the number of patients receiving medication for oral candidiasis after ICS initiation by the number of patients receiving the same medication before ICS initiation. Sub-analyses were conducted to compare the relative risks at several time points after ICS initiation and to account for therapy persistence by only including chronic users of ICS. A multivariate logistic regression model was used to identify predictive factors. A total of 52,279 incident users of ICS therapy were identified, of which 1,081 received medication for oral candidiasis up to 1 year before or after ICS initiation. A total of 701 patients received medication for oral candidiasis after ICS initiation, while 361 received these medications in the reversed sequence, resulting in a sequence ratio (SR) of 1.94 (95 % CI 1.71-2.21). In the first 3 months after ICS initiation, the SR was 2.72 (95 % CI 2.19-3.38) and then decreased to 1.47 (95 % CI 1.11-1.95) 9-12 months after ICS initiation. Predictive factors were higher daily dose of ICS and concomitant use of oral corticosteroids. This study found a significant and clinically relevant increased number of patients receiving medication for oral candidiasis in the first year after therapy initiation with ICS. Relative risk is highest in the first 3 months, but remains increased up to at least 1 year after ICS initiation. This study stresses the need for patient education and inhalation instruction.

Assessment of Durable SiC JFET Technology for +600 C to -125 C Integrated Circuit Operation

NASA Technical Reports Server (NTRS)

Neudeck, P. G.; Krasowski, M. J.; Prokop, N. F.

2011-01-01

Electrical characteristics and circuit design considerations for prototype 6H-SiC JFET integrated circuits (ICs) operating over the broad temperature range of -125 C to +600 C are described. Strategic implementation of circuits with transistors and resistors in the same 6H-SiC n-channel layer enabled ICs with nearly temperature-independent functionality to be achieved. The frequency performance of the circuits declined at temperatures increasingly below or above room temperature, roughly corresponding to the change in 6H-SiC n-channel resistance arising from incomplete carrier ionization at low temperature and decreased electron mobility at high temperature. In addition to very broad temperature functionality, these simple digital and analog demonstration integrated circuits successfully operated with little change in functional characteristics over the course of thousands of hours at 500 C before experiencing interconnect-related failures. With appropriate further development, these initial results establish a new technology foundation for realizing durable 500 C ICs for combustion engine sensing and control, deep-well drilling, and other harsh-environment applications.

Interpersonal Callousness and Co-Occurring Anxiety: Developmental Validity of an Adolescent Taxonomy

PubMed Central

2016-01-01

Growing evidence suggests heterogeneity within interpersonal-callous (IC) youth based on co-occurring anxiety. The developmental validity of this proposed taxonomy remains unclear however, as most previous research is cross-sectional and/or limited to adolescence. We aimed to identify low-anxiety (IC/ANX−) and high-anxiety (IC/ANX+) IC variants, and compare these groups on (a) early risk exposures, (b) psychiatric symptoms from midchildhood to early adolescence, and (c) school-based functioning. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective epidemiological birth cohort, model-based cluster analysis was performed on children with complete age-13 IC and anxiety scores (n = 6,791). Analysis of variance was used to compare resulting clusters on (a) prenatal and postnatal family adversity and maternal psychopathology, and harsh parenting; (b) developmental differences in attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD), emotional difficulties, and low pro-social behavior at 7, 10, and 13 years; and (c) teacher-reported discipline problems, along with standardized test performance. We identified a 4-cluster solution: “typical,” “low,” “IC/ANX−”, and “IC/ANX+.” IC/ANX+ youth showed the highest prenatal and postnatal levels of family adversity and maternal psychopathology, highest levels of ADHD, CD, ODD, and emotional difficulties, greatest discipline problems, and lowest national test scores (all p < .001). IC/ANX+ also showed a distinct pattern of increasing psychopathology from age 7 to 13 years. Adolescent IC subtypes were successfully validated in ALSPAC across multiple raters using prenatal and early postnatal risk, repeated measures of psychopathology, and school-based outcomes. Greater prenatal environmental risk among IC/ANX+ youth suggests an important target for early intervention. PMID:27977232

Global structure of mantle isotopic heterogeneity and its implications for mantle differentiation and convection

NASA Astrophysics Data System (ADS)

Iwamori, Hikaru; Albaréde, Francis; Nakamura, Hitomi

2010-11-01

In order to further our understanding of the global geochemical structure and mantle dynamics, a global isotopic data set of oceanic basalts was analyzed by Independent Component Analysis (ICA), a relatively new method of multivariate analysis. The data set consists of 2773 mid-ocean ridge basalts (MORB) and 1515 ocean island basalts (OIB) with five isotopic ratios of Pb, Nd and Sr. The data set spatially covers the major oceans and enables us to compare the results with global geophysical observations. Three independent components (ICs) have been found, two of which are essentially identical to those previously found for basalts from the Atlantic and Indian Oceans. The two ICs (IC1 and IC2) span a compositional plane that accounts for 95.7% of the sample variance, while the third IC (IC3) accounts for 3.7%. Based on the geochemical nature of ICs and a forward model concerning trace elemental and isotopic compositions, the origin of the ICs is discussed. IC1 discriminates OIB from MORB, and may be related to elemental fractionation associated with melting and the subsequent radiogenic in growth with an average recycling time of 0.8 to 2.4 Ga. IC2 tracks the regional provenance of both MORB and OIB and may be related to aqueous fluid-rock interaction and the subsequent radiogenic ingrowth with an average recycling time of 0.3 to 0.9 Ga. IC3 fingerprints upper continental crustal material and its high value appears in limited geographical and tectonic settings. Variations in the melt component (IC1) and in the aqueous fluid component (IC2) inherited in the mantle most likely reflect mid-ocean ridge and subduction zone processes, respectively. Long-term accumulation of dense materials rich in the IC1 melt component at the base of the convective mantle accounts for its longer recycling time with respect to that for less dense materials rich in the aqueous fluid component (IC2). IC2 broadly correlates with the seismic velocity structures of the lowermost mantle and electric conductivity around the mantle transition zones. We propose that IC2 reflects hydrogen distribution within the mantle and that several global domains enriched in hydrogen could exist as vertical sectors extending all the way down to the core-mantle boundary.

What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis

PubMed Central

Ribassin-Majed, Laureen; Marguet, Sophie; Lee, Anne W.M.; Ng, Wai Tong; Ma, Jun; Chan, Anthony T.C.; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T.T.; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L.W.; Cheah, Shie-Lee; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Bourhis, Jean; Pignon, Jean Pierre

2017-01-01

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC. PMID:27918720

Somatoform disorder as a predictor of interstitial cystitis/bladder pain syndrome: Evidence from a nested case-control study and a retrospective cohort study.

PubMed

Chen, I-Chun; Lee, Ming-Huei; Lin, Hsuan-Hung; Wu, Shang-Liang; Chang, Kun-Min; Lin, Hsiu-Ying

2017-05-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) has several well-known comorbid psychiatric manifestations, including insomnia, anxiety, and depression. We hypothesized that somatoform disorder, which is a psychosomatic disease, can be used as a sensitive psychiatric phenotype of IC/BPS. We investigated whether somatoform disorder increases the risk of IC/BPS.A nested case-control study and a retrospective cohort study were followed up over a 12-year period (2002-2013) in the Taiwan Health Insurance Reimbursement Database. In the nested case-control study, 1612 patients with IC/BPS were matched in a 1:2 ratio to 3224 controls based on propensity scores. The odds ratio for somatoform disorder was calculated using conditional logistic regression analysis. In the retrospective cohort study, 1436 patients with somatoform disorder were matched in a 1:2 ratio to 2872 patients with nonsomatoform disorder based on propensity scores. Cox regression analysis was used to estimate the hazard ratio associated with the development of IC/BPS in patients with somatoform disorder, and the cumulative survival probability was tested using the Kaplan-Meier analysis.We found that the odds ratio for somatoform disorder was 2.46 (95% confidence interval [CI], 1.05-5.76). Although the average time until IC/BPS development in the control subjects was 11.5 ± 1.3 years, this interval was shorter in patients with somatoform disorder (6.3 ± 3.6 years). The hazard ratio for developing IC/BPS was 2.50 (95% CI 1.23-5.58); the adjusted hazard ratio was 2.26 (95% CI 1.002-5.007). The patients and controls also differed significantly in their cumulative survival probability for IC/BPS (log rank P < .05).Evidence from the nested case-control study and retrospective cohort study consistently indicated that somatoform disorder increases the risk for IC/BPS. Our study suggests that somatoform disorder can be used as a sensitive psychiatric phenotype to predict IC/BPS. Any past history of somatoform disorder should be documented while examining patients with IC/BPS.

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

PubMed Central

Hahn, Juliane; Seeber, Frank; Kolodziej, Herbert; Ignatius, Ralf; Laue, Michael; Aebischer, Toni; Klotz, Christian

2013-01-01

Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC5024h = 2.8 µM) being more sensitive than WB-C6 (IC5024h = 6.2 µM). The effect was significantly more potent compared to MTZ (IC5024h = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis. PMID:23977083

[Health personnel assessment about medical order entry systems of pharmacologic treatments in hospitalized patients].

PubMed

Villamañán, E; Larrubia, Y; Ruano, M; Moro, M; Sierra, A; Pérez, E; Herrero, A; Álvarez-Sala, R

2013-01-01

to evaluate health personnel perceptions about medical order entry systems concerning the effect on workflow, medication errors risk and assessment of its potential advantages. A cross-section opinion interview was conducted in a tertiary care hospital. Questionnaire consisted of three sections: perception of its effect on workflow, influence on medication error risk and assessment of potential advantages. We also asked them to assess drawbacks and provide suggestions about this prescription system. 76 health professionals were interviewed (58 physicians, 9 pharmacists and 9 nurses). They were satisfied mainly due to decrease the workload (85.5%; IC 95%: 75.58-92.55). They thought that the main characteristics that contribute to reduce medication errors are clinical decision supports related to predefined aspects which the program provided by default. Among potential benefits of medical order entry systems, legibility and warnings triggered by the program (98.7%; IC 95%: 92.90-99.97 and 97,4%; IC 95%: 90.81-99.68 respectively) were the most valuable. High technology dependence, IT failures and lack of infrastructure and medication therapy discontinuities at times of transition between different hospitals' units were the main drawbacks considered. The most repeated suggestion was related to the improvement of links between other health informatics applications used in the hospital. health personnel were highly satisfied with the CPOE system, which is considered to be effective and safe. Technology dependence and IT failures were the main disadvantages reported. According to them, a greater coordination and unification of all software applications available in the hospital would be desirable. Copyright © 2012 SECA. Published by Elsevier Espana. All rights reserved.

Influence of heart failure on resting lung volumes in patients with COPD

PubMed Central

de Souza, Aline Soares; Sperandio, Priscila Abreu; Mazzuco, Adriana; Alencar, Maria Clara; Arbex, Flávio Ferlin; de Oliveira, Mayron Faria; O'Donnell, Denis Eunan; Neder, José Alberto

2016-01-01

ABSTRACT Objective: To evaluate the influence of chronic heart failure (CHF) on resting lung volumes in patients with COPD, i.e., inspiratory fraction-inspiratory capacity (IC)/TLC-and relative inspiratory reserve-[1 − (end-inspiratory lung volume/TLC)]. Methods: This was a prospective study involving 56 patients with COPD-24 (23 males/1 female) with COPD+CHF and 32 (28 males/4 females) with COPD only-who, after careful clinical stabilization, underwent spirometry (with forced and slow maneuvers) and whole-body plethysmography. Results: Although FEV1, as well as the FEV1/FVC and FEV1/slow vital capacity ratios, were higher in the COPD+CHF group than in the COPD group, all major "static" volumes-RV, functional residual capacity (FRC), and TLC-were lower in the former group (p < 0.05). There was a greater reduction in FRC than in RV, resulting in the expiratory reserve volume being lower in the COPD+CHF group than in the COPD group. There were relatively proportional reductions in FRC and TLC in the two groups; therefore, IC was also comparable. Consequently, the inspiratory fraction was higher in the COPD+CHF group than in the COPD group (0.42 ± 0.10 vs. 0.36 ± 0.10; p < 0.05). Although the tidal volume/IC ratio was higher in the COPD+CHF group, the relative inspiratory reserve was remarkably similar between the two groups (0.35 ± 0.09 vs. 0.44 ± 0.14; p < 0.05). Conclusions: Despite the restrictive effects of CHF, patients with COPD+CHF have relatively higher inspiratory limits (a greater inspiratory fraction). However, those patients use only a part of those limits, probably in order to avoid critical reductions in inspiratory reserve and increases in elastic recoil. PMID:27832235

Ex Vivo Susceptibility of Plasmodium falciparum to Antimalarial Drugs in Western, Northern, and Eastern Cambodia, 2011-2012: Association with Molecular Markers

PubMed Central

Lim, Pharath; Dek, Dalin; Try, Vorleak; Eastman, Richard T.; Chy, Sophy; Sreng, Sokunthea; Suon, Seila; Mao, Sivanna; Sopha, Chantha; Sam, Baramey; Ashley, Elizabeth A.; Miotto, Olivo; Dondorp, Arjen M.; White, Nicholas J.; Su, Xin-zhuan; Char, Meng Chuor; Anderson, Jennifer M.; Amaratunga, Chanaki; Menard, Didier

2013-01-01

In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the ex vivo 50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P ≤ 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The ex vivo IC50 and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance. PMID:23939897

Epimutation profiling in Beckwith-Wiedemann syndrome: relationship with assisted reproductive technology

PubMed Central

2013-01-01

Background Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with abnormalities in 11p15.5 imprinted genes. The most common cause is loss of methylation (epimutation) at the imprinting control centre 2 (IC2/KvDMR1). Most IC2 epimutations occur sporadically but an association with conception after assisted reproductive technologies (ART) has been reported. A subgroup of IC2 epimutation cases also harbour epimutations at other imprinting centres (ICs) outside of 11p15.5. We have investigated the relationship between these multiple epimutation cases (ME+), history of ART and clinical phenotype in a cohort of 187 BWS IC2 epimutation patients. Results Methylation analysis at PLAGL1, MEST and IGF2R ICs demonstrated an over-representation of patients with abnormally low methylation (8.5%, 12% and 6% respectively). At IGF2R some patients (2%) had gain of methylation but this was also detected in controls. Though there were no significant correlations between the methylation index (MIs) at the three ICs tested, a subset of patients appeared to be susceptible to multiple epimutations (ME+) and 21.2% of ME + patients had been conceived by ART compared to 4.5% (P = 0.0033) without additional epimutations. Methylation array profiling (Illumina Goldengate®) of patients and controls (excluding 11p15.5 loci) demonstrated significant differences between patients and controls. No significant associations were found between aspects of the BWS phenotype and individual epimutations but we describe a case presenting with a post-ART BWS-like phenotype in which molecular analysis demonstrated loss of paternal allele methylation at the 11p15.5 IC1 locus (IC1 regulates imprinting of IGF2 and H19). Loss of paternal allele methylation at the IC1 is the molecular finding associated with Silver-Russell syndrome whereas BWS is associated with gain of maternal allele methylation at IC1. Further analysis demonstrated epimutations at PLAGL1 and MEST consistent with the hypothesis that the presence of multiple epimutations may be of clinical relevance. Conclusions These findings suggest that the ME + subgroup of BWS patients are preferentially, but not exclusively, associated with a history of ART and that, though at present, there are no clear epigenotype-phenotype correlations for ME + BWS patients, non-11p15.5 IC epimutations can influence clinical phenotype. PMID:24325814

Mechanisms of activation of the paternally expressed genes by the Prader-Willi imprinting center in the Prader-Willi/Angelman syndromes domains

PubMed Central

Rabinovitz, Shiri; Kaufman, Yotam; Ludwig, Guy; Razin, Aharon; Shemer, Ruth

2012-01-01

The Prader-Willi syndrome/Angelman syndrome (PWS/AS) imprinted domain is regulated by a bipartite imprinting control center (IC) composed of a sequence around the SNRPN promoter (PWS-IC) and a 880-bp sequence located 35 kb upstream (AS-IC). The AS-IC imprint is established during gametogenesis and confers repression upon PWS-IC on the maternal allele. Mutation at PWS-IC on the paternal allele leads to gene silencing across the entire PWS/AS domain. This silencing implies that PWS-IC functions on the paternal allele as a bidirectional activator. Here we examine the mechanism by which PWS-IC activates the paternally expressed genes (PEGs) using transgenes that include the PWS-IC sequence in the presence or absence of AS-IC and NDN, an upstream PEG, as an experimental model. We demonstrate that PWS-IC is in fact an activator of NDN. This activation requires an unmethylated PWS-IC in the gametes and during early embryogenesis. PWS-IC is dispensable later in development. Interestingly, a similar activation of a nonimprinted gene (APOA1) was observed, implying that PWS-IC is a universal activator. To decipher the mechanism by which PWS-IC confers activation of remote genes, we performed methylated DNA immunoprecipitation (MeDIP) array analysis on lymphoblast cell lines that revealed dispersed, rather than continued differential methylation. However, chromatin conformation capture (3c) experiments revealed a physical interaction between PWS-IC and the PEGs, suggesting that activation of PEGs may require their proximity to PWS-IC. PMID:22529396

Yield modeling of acoustic charge transport transversal filters

NASA Technical Reports Server (NTRS)

Kenney, J. S.; May, G. S.; Hunt, W. D.

1995-01-01

This paper presents a yield model for acoustic charge transport transversal filters. This model differs from previous IC yield models in that it does not assume that individual failures of the nondestructive sensing taps necessarily cause a device failure. A redundancy in the number of taps included in the design is explained. Poisson statistics are used to describe the tap failures, weighted over a uniform defect density distribution. A representative design example is presented. The minimum number of taps needed to realize the filter is calculated, and tap weights for various numbers of redundant taps are calculated. The critical area for device failure is calculated for each level of redundancy. Yield is predicted for a range of defect densities and redundancies. To verify the model, a Monte Carlo simulation is performed on an equivalent circuit model of the device. The results of the yield model are then compared to the Monte Carlo simulation. Better than 95% agreement was obtained for the Poisson model with redundant taps ranging from 30% to 150% over the minimum.

Patterns and determinants of use of pharmacological therapies for intermittent claudication in PAD outpatients: results of the IDOMENEO study.

PubMed

Cimminiello, Claudio; Polo Friz, Hernan; Marano, Giuseppe; Arpaia, Guido; Boracchi, Patrizia; Spezzigu, Gabriella; Visonà, Adriana

2017-06-01

Peripheral arterial disease (PAD) usually presents with intermittent claudication (IC). The aim of the present study was to assess, in clinical practice, the pattern of use of pharmacological therapies for IC in stable PAD outpatients. A propensity analysis was performed using data from the IDOMENEO study, an observational prospective multicenter cohort study. The association between any pharmacological symptomatic IC therapy with different variables was investigated using generalized linear mixed models with pharmacological therapy as response variable and binomial error. Study population: 213 patients, male sex 147 (69.0%), mean age 70.0±8.6 years. Only 36.6% was under pharmacological treatment for IC, being cilostazol the most used medication (21.6%). Univariate analysis showed a probability of a patient of being assigned to any pharmacological symptomatic IC therapy of 67.0% when Ankle-Brachial Index (ABI) <0.6 and 29.8% when ABI>0.6 (P=0.0048), and a propensity to avoid pharmacological treatment for patients with a high number of drugs to treat cardiovascular risk factors (probability of 55.2% for <4 drugs and 19.6% for >4 drugs, P=0.0317). Multivariate analysis confirmed a higher probability of assigning treatment for ABI<0.6 (P=0.0274), and a trend to a lower probability in patients under polypharmacy (>4 drugs: OR=0.13, P=0.0546). In clinical practice, only one third of stable outpatients with IC used symptomatic pharmacological therapy for IC. We found a propensity of clinicians to assign any symptomatic pharmacological IC therapy to patients with lower values of ABI and a propensity to avoid this kind of treatment in patients under polypharmacy.

The Implicit Curriculum Survey: An Examination of the Psychometric Properties

ERIC Educational Resources Information Center

Grady, Melissa D.; Swick, Danielle C.; Powers, Joelle D.

2018-01-01

This study examined the psychometric properties of the Implicit Curriculum Survey (ICS) using an exploratory factor analysis (EFA). Students enrolled in four different MSW programs (N = 262) from different geographic locations completed the ICS, which is a Web-based survey. The domains of the ICS include field, academics, community, diversity,…

Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity.

PubMed

Galioto, Rachel; O'Leary, Kevin C; Thomas, J Graham; Demos, Kathryn; Lipton, Richard B; Gunstad, John; Pavlović, Jelena M; Roth, Julie; Rathier, Lucille; Bond, Dale S

2017-12-01

Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration. Women (n = 105) aged 18-50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety. Participants on average had BMI of 35.1 ± 6.5 kg/m 2 and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (β = .241, SE = .14, p = .03) and magnification subscale (β = .311, SE = .51, p < .01) scores were significant independent correlates of longer attack duration. IC interacted with total PCS (β = 1.106, SE = .001, p = .03) rumination (β = 1.098, SE = .001, p = .04), and helplessness (β = 1.026, SE = .001, p = .04) subscale scores to predict headache pain intensity, such that the association between PC and pain intensity became more positive at lower levels of IC. Results showed that lower IC interacted with higher PC, both overall and specific subcomponents, to predict higher pain intensity during migraine attacks. Future studies are needed to determine whether interventions to improve IC could lead to less painful migraine attacks via improvements in PC.

Genome expression analysis in yeast reveals novel transcriptional regulation by inositol and choline and new regulatory functions for Opi1p, Ino2p, and Ino4p.

PubMed

Santiago, Teresa C; Mamoun, Choukri Ben

2003-10-03

In Saccharomyces cerevisiae, genes encoding phospholipid-synthesizing enzymes are regulated by inositol and choline (IC). The current model suggests that when these precursors become limiting, the transcriptional complex Ino2p-Ino4p activates the expression of these genes, whereas repression requires Opi1p and occurs when IC are available. In this study, microarray-based expression analysis was performed to assess the global transcriptional response to IC in a wild-type strain and in the opi1delta, ino2delta, and ino4delta null mutant strains. Fifty genes were either activated or repressed by IC in the wild-type strain, including three already known IC-repressed genes. We demonstrated that the IC response was not limited to genes involved in membrane biogenesis, but encompassed various metabolic pathways such as biotin synthesis, one-carbon compound metabolism, nitrogen-containing compound transport and degradation, cell wall organization and biogenesis, and acetyl-CoA metabolism. The expression of a large number of IC-regulated genes did not change in the opi1delta, ino2delta, and ino4delta strains, thus implicating new regulatory elements in the IC response. Our studies revealed that Opi1p, Ino2p, and Ino4p have dual regulatory activities, acting in both positive and negative transcriptional regulation of a large number of genes, most of which are not regulated by IC and only a subset of which is involved in membrane biogenesis. These data provide the first global response profile of yeast to IC and reveal novel regulatory mechanisms by these precursors.

Association Between Macrominerals Intake and Changes in Internal Carotid Artery-Intima Media Thickness in POST Ischemic Stroke Patients

NASA Astrophysics Data System (ADS)

Pudjonarko, Dwi; Tugasworo, Dodik; Silaen, Rumintang

2017-02-01

Carotid Intima Media Thickness (C-IMT) has been widely used as marker for atherosclerosis. Previous studies on minerals intake and its association with C-IMT revealed various. Most of the studies showed inconsistent results. The aim of this study is to determine wether macro minerals intake is related to internal carotid-intima media thickness (IC-IMT). This is a longitudinal study, pre test post test design conducted in Neurology clinic, Kariadi hospital, Semarang from June to December 2014. Subjects were 22 post ischemic stroke patients. Minerals intake and IC-IMT was measured using Food Frequency Questionnaire and Duplex Carotid Ultrasonography. Statistical analysis was performed using Chi-Square, Fisher Exact and Logistic Regression test. Subjects included in this study were 17 male subjects (77.3%) and 5 female subjects (22.7%). Mean of IC-IMT in female subjects was found to be higher than in male. Mean of total IC-IMT was increased after a period of six months (0.96±0.80 to 0.97±0.21 mm). There were significant association between calcium as well as sodium intakes and IC-IMT. In contrast, there were no association between magnesium as well as potassium intake and IC-IMT. Multivariate analysis suggest that sodium intake (OR=26.828) was the most influencing factor for IC-IMT, followed by calcium intake (OR=0.042). Calcium as well as potassium intake were independently associated with IC-IMT. Magnecium as well as sodium intake were not independently associated with IC-IMT changes. Sodium intake was the most influencing variable to IC-IMT changes, followed by calcium intake.

Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease.

PubMed

Tong, Ming; Leão, Raiane; Vimbela, Gina V; Yalcin, Emine B; Kay, Jared; Krotow, Alexander; de la Monte, Suzanne M

2017-07-01

White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

[Extraction of evoked related potentials by using the combination of independent component analysis and wavelet analysis].

PubMed

Zou, Ling; Chen, Shuyue; Sun, Yuqiang; Ma, Zhenghua

2010-08-01

In this paper we present a new method of combining Independent Component Analysis (ICA) and Wavelet de-noising algorithm to extract Evoked Related Potentials (ERPs). First, the extended Infomax-ICA algorithm is used to analyze EEG signals and obtain the independent components (Ics); Then, the Wave Shrink (WS) method is applied to the demixed Ics as an intermediate step; the EEG data were rebuilt by using the inverse ICA based on the new Ics; the ERPs were extracted by using de-noised EEG data after being averaged several trials. The experimental results showed that the combined method and ICA method could remove eye artifacts and muscle artifacts mixed in the ERPs, while the combined method could retain the brain neural activity mixed in the noise Ics and could extract the weak ERPs efficiently from strong background artifacts.

Intra-operative cell salvage in urological surgery; a systematic review and meta-analysis of comparative studies.

PubMed

Kinnear, Ned; O'Callaghan, Michael; Hennessey, Derek; Liddell, Heath; Newell, Bradley; Bolt, John; Lawrentschuk, Nathan

2018-05-03

To systematically evaluate the safety and efficacy of intra-operative cell salvage (ICS) in urology. A search of Medline, Embase and Cochrane Library to August 2017 was performed using methods pre-published on PROSPERO. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Eligible titles were comparative studies published in English utilising ICS in urology. Primary outcomes were allogeneic transfusion rates (ATR) and tumour recurrence. Secondary outcomes were complications and cost. Fourteen observational studies were identified, totaling 4,536 patients. ICS was compared to no blood conservation technique (seven studies), pre-operative autologous donation (PAD) (five) or both (two). Cohorts underwent open prostatectomy (eleven studies), open cystectomy (two) or open partial nephrectomy (one). Meta-analysis was possible only for ATR within prostatectomy studies. In this setting, ICS reduced ATR compared with no blood conservation technique (OR 0.34, 95% CI 0.15-0.76) but not PAD (OR 0.76, 95% CI 0.39-1.31). In the non-prostatectomy setting, ATR amongst ICS patients was significantly higher or similar in one and two studies respectively. Tumour recurrence was found to be significantly less common (two studies), similar (eight) or not measured (four). All six studies reporting complications found no difference for ICS cohorts. Regarding cost, one study from 1995 found ICS more expensive than PAD, while two more recent studies found ICS cheaper than no blood conservation technique. Due to inter-study heterogeneity, meta-analyses were not possible for recurrence, complications or cost. Low level evidence exists that compared with other blood conservation techniques, ICS reduces ATR and cost while not affecting complications. It does not appear to increase tumour recurrence post-prostatectomy, although follow-up durations are short. Small size and short follow-up negate conclusions on recurrence following nephrectomy or cystectomy. Randomised trials with long term follow-up evaluating ICS in urology are required. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Analysis of informed consent readibility in intensive care].

PubMed

Ramírez-Puerta, M R; Fernández-Fernández, R; Frías-Pareja, J C; Yuste-Ossorio, M E; Narbona-Galdó, S; Peñas-Maldonado, L

2013-11-01

To analyze the readability of informed consent documents (IC) used in an intensive care department and in the Andalusian Healthcare System (AHS). A descriptive study was carried out. The Intensive Care Unit of a tertiary Hospital, and the AHS. A review and analysis was made of the existing 14 IC models in the Intensive Care Unit and of another 14 IC models offered by the AHS, using the following readability scores: Flesch, Sentence complexity, LEGIN, Fernández-Huerta, Szigriszt and INFLESZ. Twenty-four IC (85.7%) failed to satisfy some of the indexes, while three (10.7%) did not satisfy any of them. Four documents (14.3%) satisfied all the indexes analyzed, and therefore are easy to understand. Flesch score: satisfied by one of the ICU IC (7.1%) and by three of the AHS documents (21.4%). Sentence complexity score: satisfied by 11 of the ICU IC (78.6%) and by 13 of the AHS documents (92.8%). Fernández-Huerta score: satisfied by four of the ICU IC (28.6%) and by 13 of the AHS documents (92.8%). Szigriszt score: satisfied by two of the ICU IC (14.3%) and by 11 of the AHS documents (64.3%). INFLESZ score: satisfied by two of the ICU IC (14.3%) and by 10 of the AHS documents (71.4%). The documents analyzed are generally difficult to read and understand by most people, and do not satisfy the basic purpose for which they were drafted. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Risk Scan: A Review of Risk Assessment Capability and Maturity within the Canadian Safety and Security Program

DTIC Science & Technology

2014-06-01

SCADA / ICS Cyber Test Lab initiated in 2013 Psychosocial – academic research exists,; opportunity for sharing and developing impact assessment...ecosystems and species at risk), accidents / system failure (rail; pipelines ; ferries CSSP strategy for the North Focus on regional l(and local) problem...Guidance; business planning; environmental scan; proposal evaluation; and performance measurement Program Risk Management – Guidelines for project

Reliability, Validity, and Factor Structure of the Imaginative Capability Scale

ERIC Educational Resources Information Center

Liang, Chaoyun; Chia, Tsorng-Lin

2014-01-01

Three studies were combined to test the reliability, validity, and factor structure of the imaginative capability scale (ICS). The ICS was a new self-report measure, which was developed to be empirically valid and easy to administer. Study 1 consisted in an exploratory factor analysis to determine the most appropriate structure of the ICS in a…

A Longitudinal Analysis of Anger and Inhibitory Control in Twins from 12–36 Months of Age

PubMed Central

Goldsmith, H. Hill

2010-01-01

Inhibitory control (IC) is a dimension of child temperament that involves the self-regulation of behavioral responses under some form of instruction or expectation. Although IC is posited to appear in toddlerhood, the voluntary control of emotions such as anger begins earlier. Little research has analyzed relations between emotional development in infancy and later emerging IC. We examined phenotypic associations and genetic and environmental influences on parent-and laboratory-assessed anger and IC in a twin sample from 12 to 36 months of age. Typically, twins with low levels of IC had high levels of anger. Behavioral genetic findings confirmed significant genetic influences on anger and IC as assessed by parents, and on lab-based anger assessments. Shared environmental factors contributed to twin similarity on lab-assessed anger and IC at 36 months. Phenotypic covariance between anger and IC was largely due to overlapping genetic factors for parent ratings, and environmental factors in the laboratory. PMID:21159093

The effects of iris-ciliary complex on the organ cultured rabbit ocular lens.

PubMed

Niyogi, T K; Emanuel, K; Parafina, J; Bagchi, M

1991-01-01

Freshly isolated rabbit lenses were cultured with and without attached iris-ciliary (IC)-complex for 24 hours in TC-199 medium. Subsequent morphological analysis revealed that the IC-complex cannot be maintained in serum-free medium. In addition an observed effect of the IC-complex on the co-cultured lenses could not be due only because of the cellular degeneration of the IC-complex. To test this possibility lenses with attached IC-complexes were incubated in 20% serum-containing TC-199 medium. The IC-complex cultured in 20% serum containing medium retained its normal morphology. However co-cultured lens cells displayed vacuoles and other signs of degeneration. The protein synthetic and Na+/K+ pump activities of these lenses were also significantly depressed. These data indicated that the observed effects of IC-complex on the lens were not due to its cellular degradation. Preliminary experiments showed that the IC-complex contains water soluble factor(s) which could effectively inhibit lens protein synthesis and Na+/K+ pump.

Adaptation of Sediment Connectivity Index for Swedish catchments and application for flood prediction of roads

NASA Astrophysics Data System (ADS)

Cantone, Carolina; Kalantari, Zahra; Cavalli, Marco; Crema, Stefano

2016-04-01

Climate changes are predicted to increase precipitation intensities and occurrence of extreme rainfall events in the near future. Scandinavia has been identified as one of the most sensitive regions in Europe to such changes; therefore, an increase in the risk for flooding, landslides and soil erosion is to be expected also in Sweden. An increase in the occurrence of extreme weather events will impose greater strain on the built environment and major transport infrastructures such as roads and railways. This research aimed to identify the risk of flooding at the road-stream intersections, crucial locations where water and debris can accumulate and cause failures of the existing drainage facilities. Two regions in southwest of Sweden affected by an extreme rainfall event in August 2014, were used for calibrating and testing a statistical flood prediction model. A set of Physical Catchment Descriptors (PCDs) including road and catchment characteristics was identified for the modelling. Moreover, a GIS-based topographic Index of Sediment Connectivity (IC) was used as PCD. The novelty of this study relies on the adaptation of IC for describing sediment connectivity in lowland areas taking into account contribution of soil type, land use and different patterns of precipitation during the event. A weighting factor for IC was calculated by estimating runoff calculated with SCS Curve Number method, assuming a constant value of precipitation for a given time period, corresponding to the critical event. The Digital Elevation Model of the study site was reconditioned at the drainage facilities locations to consider the real flow path in the analysis. These modifications led to highlight the role of rainfall patterns and surface runoff for modelling sediment delivery in lowland areas. Moreover, it was observed that integrating IC into the statistic prediction model increased its accuracy and performance. After the calibration procedure in one of the study areas, the model was validated in the other study area, located in the central part of Sweden, since this experienced flooding in relation to the same triggering event.

Group Independent Component Analysis (gICA) and Current Source Density (CSD) in the study of EEG in ADHD adults.

PubMed

Ponomarev, Valery A; Mueller, Andreas; Candrian, Gian; Grin-Yatsenko, Vera A; Kropotov, Juri D

2014-01-01

To investigate the performance of the spectral analysis of resting EEG, Current Source Density (CSD) and group independent components (gIC) in diagnosing ADHD adults. Power spectra of resting EEG, CSD and gIC (19 channels, linked ears reference, eyes open/closed) from 96 ADHD and 376 healthy adults were compared between eyes open and eyes closed conditions, and between groups of subjects. Pattern of differences in gIC and CSD spectral power between conditions was approximately similar, whereas it was more widely spatially distributed for EEG. Size effect (Cohen's d) of differences in gIC and CSD spectral power between groups of subjects was considerably greater than in the case of EEG. Significant reduction of gIC and CSD spectral power depending on conditions was found in ADHD patients. Reducing power in a wide frequency range in the fronto-central areas is a common phenomenon regardless of whether the eyes were open or closed. Spectral power of local EEG activity isolated by gICA or CSD in the fronto-central areas may be a suitable marker for discrimination of ADHD and healthy adults. Spectral analysis of gIC and CSD provides better sensitivity to discriminate ADHD and healthy adults. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Migratory gold resistive shorts - Chemical aspects of a failure mechanism

NASA Technical Reports Server (NTRS)

Grunthaner, F. J.; Griswold, T. W.; Clendening, P. J.

1975-01-01

Integrated-circuit devices using the Ti/W/Au metal system are subject to failure mechanisms based on electrolytic corrosion. The migratory gold resistive short (MGRS) failure mode is one example of this mechanism and results in the formation of filamentary or dendritic deposits of gold between adjacent stripes on the IC chip. This reaction requires the presence of a sufficient amount of water, a bias voltage between adjacent stripes, and the activation of the cathodic (-) stripe. Gold ions are transported from anode to cathode through a film of moisture adsorbed on the surface of the chip; halide ions are probably involved in the transfer. Their presence is verified experimentally by X-ray photoelectron spectroscopy. Some of the chemical and electrostatic factors involved in the MGRS mechanism are discussed in this paper, including the questions of a threshold level of moisture and contamination.

Accelerated stress testing of terrestrial solar cells

NASA Technical Reports Server (NTRS)

Lathrop, J. W.; Hawkins, D. C.; Prince, J. L.; Walker, H. A.

1982-01-01

The development of an accelerated test schedule for terrestrial solar cells is described. This schedule, based on anticipated failure modes deduced from a consideration of IC failure mechanisms, involves bias-temperature testing, humidity testing (including both 85-85 and pressure cooker stress), and thermal-cycle thermal-shock testing. Results are described for 12 different unencapsulated cell types. Both gradual electrical degradation and sudden catastrophic mechanical change were observed. These effects can be used to discriminate between cell types and technologies relative to their reliability attributes. Consideration is given to identifying laboratory failure modes which might lead to severe degradation in the field through second quadrant operation. Test results indicate that the ability of most cell types to withstand accelerated stress testing depends more on the manufacturer's design, processing, and worksmanship than on the particular metallization system. Preliminary tests comparing accelerated test results on encapsulated and unencapsulated cells are described.

A new statistical methodology predicting chip failure probability considering electromigration

NASA Astrophysics Data System (ADS)

Sun, Ted

In this research thesis, we present a new approach to analyze chip reliability subject to electromigration (EM) whose fundamental causes and EM phenomenon happened in different materials are presented in this thesis. This new approach utilizes the statistical nature of EM failure in order to assess overall EM risk. It includes within-die temperature variations from the chip's temperature map extracted by an Electronic Design Automation (EDA) tool to estimate the failure probability of a design. Both the power estimation and thermal analysis are performed in the EDA flow. We first used the traditional EM approach to analyze the design with a single temperature across the entire chip that involves 6 metal and 5 via layers. Next, we used the same traditional approach but with a realistic temperature map. The traditional EM analysis approach and that coupled with a temperature map and the comparison between the results of considering and not considering temperature map are presented in in this research. A comparison between these two results confirms that using a temperature map yields a less pessimistic estimation of the chip's EM risk. Finally, we employed the statistical methodology we developed considering a temperature map and different use-condition voltages and frequencies to estimate the overall failure probability of the chip. The statistical model established considers the scaling work with the usage of traditional Black equation and four major conditions. The statistical result comparisons are within our expectations. The results of this statistical analysis confirm that the chip level failure probability is higher i) at higher use-condition frequencies for all use-condition voltages, and ii) when a single temperature instead of a temperature map across the chip is considered. In this thesis, I start with an overall review on current design types, common flows, and necessary verifications and reliability checking steps used in this IC design industry. Furthermore, the important concepts about "Scripting Automation" which is used in all the integration of using diversified EDA tools in this research work are also described in detail with several examples and my completed coding works are also put in the appendix for your reference. Hopefully, this construction of my thesis will give readers a thorough understanding about my research work from the automation of EDA tools to the statistical data generation, from the nature of EM to the statistical model construction, and the comparisons among the traditional EM analysis and the statistical EM analysis approaches.

Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics.

PubMed

Zambenedetti, Miriam Ribas; Pavoni, Daniela Parada; Dallabona, Andreia Cristine; Dominguez, Alejandro Correa; Poersch, Celina de Oliveira; Fragoso, Stenio Perdigão; Krieger, Marco Aurélio

2017-05-01

Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections. In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window. The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test. The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses. The MS2 genome was cloned into the pET47b(+) plasmid, generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase. These particles were used as non-competitive IC in assays for RNA virus diagnostics. In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle. The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection. We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations. In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol. An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses.

Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics

PubMed Central

Zambenedetti, Miriam Ribas; Pavoni, Daniela Parada; Dallabona, Andreia Cristine; Dominguez, Alejandro Correa; Poersch, Celina de Oliveira; Fragoso, Stenio Perdigão; Krieger, Marco Aurélio

2017-01-01

BACKGROUND Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections. In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window. The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test. OBJECTIVES The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses. METHODS The MS2 genome was cloned into the pET47b(+) plasmid, generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase. These particles were used as non-competitive IC in assays for RNA virus diagnostics. In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle. The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection. FINDINGS We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations. In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol. An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses. PMID:28403327

Identifying reliable independent components via split-half comparisons

PubMed Central

Groppe, David M.; Makeig, Scott; Kutas, Marta

2011-01-01

Independent component analysis (ICA) is a family of unsupervised learning algorithms that have proven useful for the analysis of the electroencephalogram (EEG) and magnetoencephalogram (MEG). ICA decomposes an EEG/MEG data set into a basis of maximally temporally independent components (ICs) that are learned from the data. As with any statistic, a concern with using ICA is the degree to which the estimated ICs are reliable. An IC may not be reliable if ICA was trained on insufficient data, if ICA training was stopped prematurely or at a local minimum (for some algorithms), or if multiple global minima were present. Consequently, evidence of ICA reliability is critical for the credibility of ICA results. In this paper, we present a new algorithm for assessing the reliability of ICs based on applying ICA separately to split-halves of a data set. This algorithm improves upon existing methods in that it considers both IC scalp topographies and activations, uses a probabilistically interpretable threshold for accepting ICs as reliable, and requires applying ICA only three times per data set. As evidence of the method’s validity, we show that the method can perform comparably to more time intensive bootstrap resampling and depends in a reasonable manner on the amount of training data. Finally, using the method we illustrate the importance of checking the reliability of ICs by demonstrating that IC reliability is dramatically increased by removing the mean EEG at each channel for each epoch of data rather than the mean EEG in a prestimulus baseline. PMID:19162199

SESNPCA: Principal Component Analysis Applied to Stripped-Envelope Core-Collapse Supernovae

NASA Astrophysics Data System (ADS)

Williamson, Marc; Bianco, Federica; Modjaz, Maryam

2018-01-01

In the new era of time-domain astronomy, it will become increasingly important to have rigorous, data driven models for classifying transients, including supernovae (SNe). We present the first application of principal component analysis (PCA) to stripped-envelope core-collapse supernovae (SESNe). Previous studies of SNe types Ib, IIb, Ic, and broad-line Ic (Ic-BL) focus only on specific spectral features, while our PCA algorithm uses all of the information contained in each spectrum. We use one of the largest compiled datasets of SESNe, containing over 150 SNe, each with spectra taken at multiple phases. Our work focuses on 49 SNe with spectra taken 15 ± 5 days after maximum V-band light where better distinctions can be made between SNe type Ib and Ic spectra. We find that spectra of SNe type IIb and Ic-BL are separable from the other types in PCA space, indicating that PCA is a promising option for developing a purely data driven model for SESNe classification.

How thin barrier metal can be used to prevent Co diffusion in the modern integrated circuits?

NASA Astrophysics Data System (ADS)

Dixit, Hemant; Konar, Aniruddha; Pandey, Rajan; Ethirajan, Tamilmani

2017-11-01

In modern integrated circuits (ICs), billions of transistors are connected to each other via thin metal layers (e.g. copper, cobalt, etc) known as interconnects. At elevated process temperatures, inter-diffusion of atomic species can occur among these metal layers, causing sub-optimal performance of interconnects, which may lead to the failure of an IC. Thus, typically a thin barrier metal layer is used to prevent the inter-diffusion of atomic species within interconnects. For ICs with sub-10 nm transistors (10 nm technology node), the design rule (thickness scaling) demands the thinnest possible barrier layer. Therefore, here we investigate the critical thickness of a titanium-nitride (TiN) barrier that can prevent the cobalt diffusion using multi-scale modeling and simulations. First, we compute the Co diffusion barrier in crystalline and amorphous TiN with the nudged elastic band method within first-principles density functional theory simulations. Later, using the calculated activation energy barriers, we quantify the Co diffusion length in the TiN metal layer with the help of kinetic Monte Carlo simulations. Such a multi-scale modelling approach yields an exact critical thickness of the metal layer sufficient to prevent the Co diffusion in IC interconnects. We obtain a diffusion length of a maximum of 2 nm for a typical process of thermal annealing at 400 °C for 30 min. Our study thus provides useful physical insights for the Co diffusion in the TiN layer and further quantifies the critical thickness (~2 nm) to which the metal barrier layer can be thinned down for sub-10 nm ICs.

Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

PubMed

Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S

2016-03-01

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (< 12 years), 2 adolescent (12-18 years), and 4 adults (>18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

Alpha particle-induced soft errors in microelectronic devices. I

NASA Astrophysics Data System (ADS)

Redman, D. J.; Sega, R. M.; Joseph, R.

1980-03-01

The article provides a tutorial review and trend assessment of the problem of alpha particle-induced soft errors in VLSI memories. Attention is given to an analysis of the design evolution of modern ICs, and the characteristics of alpha particles and their origin in IC packaging are reviewed. Finally, the process of an alpha particle penetrating an IC is examined.

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer.

PubMed

Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

2016-10-01

To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

PubMed

Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

2018-05-01

Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia.

PubMed

Lim, Pharath; Alker, Alisa P; Khim, Nimol; Shah, Naman K; Incardona, Sandra; Doung, Socheat; Yi, Poravuth; Bouth, Denis Mey; Bouchier, Christiane; Puijalon, Odile Mercereau; Meshnick, Steven R; Wongsrichanalai, Chansuda; Fandeur, Thierry; Le Bras, Jacques; Ringwald, Pascal; Ariey, Frédéric

2009-01-12

The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group) in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group) in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p < 0.001). This was not observed in the patients treated with AL (n = 96, p = 0.364). The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR) = 7.80 [95%CI: 2.09-29.10], N = 115), p = 0.002) but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24-4.44], N = 109, p = 0.969). This study shows that pfmdr1 copy number is a molecular marker of AM treatment failure in falciparum malaria on the Thai-Cambodian border. However, while it is associated with increased IC50 for lumefantrine, pfmdr1 copy number is not associated with AL treatment failure in the area, suggesting involvement of other molecular mechanisms in AL treatment failures in Cambodia.

15q11.2–13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain

PubMed Central

Yasui, Dag H.; Scoles, Haley A.; Horike, Shin-ichi; Meguro-Horike, Makiko; Dunaway, Keith W.; Schroeder, Diane I.; LaSalle, Janine M.

2011-01-01

Copy number variations (CNVs) within human 15q11.2–13.3 show reduced penetrance and variable expressivity in a range of neurologic disorders. Therefore, characterizing 15q11.2–13.3 chromatin structure is important for understanding the regulation of this locus during normal neuronal development. Deletion of the Prader–Willi imprinting center (PWS-IC) within 15q11.2–13.3 disrupts long-range imprinted gene expression resulting in Prader–Willi syndrome. Previous results establish that MeCP2 binds to the PWS-IC and is required for optimal expression of distal GABRB3 and UBE3A. To examine the hypothesis that MeCP2 facilitates 15q11.2–13.3 transcription by linking the PWS-IC with distant elements, chromosome capture conformation on chip (4C) analysis was performed in human SH-SY5Y neuroblastoma cells. SH-SY5Y neurons had 2.84-fold fewer 15q11.2–13.3 PWS-IC chromatin interactions than undifferentiated SH-SY5Y neuroblasts, revealing developmental chromatin de-condensation of the locus. Out of 68 PWS-IC interactions with15q11.2–13.3 identified by 4C analysis and 62 15q11.2–13.3 MeCP2-binding sites identified by previous ChIP-chip studies, only five sites showed overlap. Remarkably, two of these overlapping PWS-IC- and MeCP2-bound sites mapped to sites flanking CHRNA7 (cholinergic receptor nicotinic alpha 7) encoding the cholinergic receptor, nicotinic, alpha 7. PWS-IC interaction with CHRNA7 in neurons was independently confirmed by fluorescent in situ hybridization analysis. Subsequent quantitative transcriptional analyses of frontal cortex from Rett syndrome and autism patients revealed significantly reduced CHRNA7 expression compared with controls. Together, these results suggest that transcription of CHRNA7 is modulated by chromatin interactions with the PWS-IC. Thus, loss of long-range chromatin interactions within 15q11.2–13.3 may contribute to multiple human neurodevelopmental disorders. PMID:21840925

15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain.

PubMed

Yasui, Dag H; Scoles, Haley A; Horike, Shin-Ichi; Meguro-Horike, Makiko; Dunaway, Keith W; Schroeder, Diane I; Lasalle, Janine M

2011-11-15

Copy number variations (CNVs) within human 15q11.2-13.3 show reduced penetrance and variable expressivity in a range of neurologic disorders. Therefore, characterizing 15q11.2-13.3 chromatin structure is important for understanding the regulation of this locus during normal neuronal development. Deletion of the Prader-Willi imprinting center (PWS-IC) within 15q11.2-13.3 disrupts long-range imprinted gene expression resulting in Prader-Willi syndrome. Previous results establish that MeCP2 binds to the PWS-IC and is required for optimal expression of distal GABRB3 and UBE3A. To examine the hypothesis that MeCP2 facilitates 15q11.2-13.3 transcription by linking the PWS-IC with distant elements, chromosome capture conformation on chip (4C) analysis was performed in human SH-SY5Y neuroblastoma cells. SH-SY5Y neurons had 2.84-fold fewer 15q11.2-13.3 PWS-IC chromatin interactions than undifferentiated SH-SY5Y neuroblasts, revealing developmental chromatin de-condensation of the locus. Out of 68 PWS-IC interactions with15q11.2-13.3 identified by 4C analysis and 62 15q11.2-13.3 MeCP2-binding sites identified by previous ChIP-chip studies, only five sites showed overlap. Remarkably, two of these overlapping PWS-IC- and MeCP2-bound sites mapped to sites flanking CHRNA7 (cholinergic receptor nicotinic alpha 7) encoding the cholinergic receptor, nicotinic, alpha 7. PWS-IC interaction with CHRNA7 in neurons was independently confirmed by fluorescent in situ hybridization analysis. Subsequent quantitative transcriptional analyses of frontal cortex from Rett syndrome and autism patients revealed significantly reduced CHRNA7 expression compared with controls. Together, these results suggest that transcription of CHRNA7 is modulated by chromatin interactions with the PWS-IC. Thus, loss of long-range chromatin interactions within 15q11.2-13.3 may contribute to multiple human neurodevelopmental disorders.

Peripheral atherectomy practice patterns in the United States from the Vascular Quality Initiative.

PubMed

Mohan, Sathish; Flahive, Julie M; Arous, Edward J; Judelson, Dejah R; Aiello, Francesco A; Schanzer, Andres; Simons, Jessica P

2018-06-21

Peripheral atherectomy has been shown to have technical success in single-arm studies, but clinical advantages over angioplasty and stenting have not been demonstrated, leaving its role unclear. We sought to describe patterns of atherectomy use in a real-world U.S. cohort to understand how it is currently being applied. The Vascular Quality Initiative was queried to identify all patients who underwent peripheral vascular intervention from January 2010 to September 2016. Descriptive statistics were performed to analyze demographics of the patients, comorbidities, indication, treatment modalities, and lesion characteristics. The intermittent claudication (IC) and critical limb ischemia (CLI) cohorts were analyzed separately. Of 85,605 limbs treated, treatment indication was IC in 51% (n = 43,506) and CLI in 49% (n = 42,099). Atherectomy was used in 15% (n = 13,092) of cases, equivalently for IC (15%; n = 6674) and CLI (15%; n = 6418). There was regional variation in use of atherectomy, ranging from a low of 0% in one region to a high of 32% in another region. During the study period, there was a significant increase in the proportion of cases that used atherectomy (11% in 2010 vs 18% in 2016; P < .0001). Compared with nonatherectomy cases, those with atherectomy use had higher incidence of prior peripheral vascular intervention (IC, 55% vs 43% [P < .0001]; CLI, 47% vs 41% [P < .0001]), greater mean number of arteries treated (IC, 1.8 vs 1.6 [P < .0001]; CLI, 2.1 vs 1.7 [P < .0001]), and lower proportion of prior leg bypass (IC, 10% vs 14% [P < .0001]; CLI, 11% vs 17% [P < .0001]). There was lower incidence of failure to cross the lesion (IC, 1% vs 4% [P < .0001]; CLI, 4% vs 7% [P < .0001]) but higher incidence of distal embolization (IC, 1.9% vs 0.8% [P < .0001]; CLI, 3.0% vs 1.4% [P < .0001]) and, in the CLI cohort, arterial perforation (1.4% vs 1.0%; P = .01). Despite a lack of evidence for atherectomy over angioplasty and stenting, its use has increased across the United States from 2010 to 2016. It is applied equally to IC and CLI populations, with no identifiable pattern of comorbidities or lesion characteristics, suggesting that indications are not clearly delineated or agreed on. This study places impetus on further understanding of the optimal role for atherectomy and its long-term clinical benefit in the management of peripheral arterial disease. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Integrated Circuit (3D IC) Key Technology: Through-Silicon Via (TSV).

PubMed

Shen, Wen-Wei; Chen, Kuan-Neng

2017-12-01

3D integration with through-silicon via (TSV) is a promising candidate to perform system-level integration with smaller package size, higher interconnection density, and better performance. TSV fabrication is the key technology to permit communications between various strata of the 3D integration system. TSV fabrication steps, such as etching, isolation, metallization processes, and related failure modes, as well as other characterizations are discussed in this invited review paper.

Simultaneous and iterative weighted regression analysis of toxicity tests using a microplate reader.

PubMed

Galgani, F; Cadiou, Y; Gilbert, F

1992-04-01

A system is described for determination of LC50 or IC50 by an iterative process based on data obtained from a plate reader using a marine unicellular alga as a target species. The esterase activity of Tetraselmis suesica on fluorescein diacetate as a substrate was measured using a fluorescence titerplate. Simultaneous analysis of results was performed using an iterative process adopting the sigmoid function Y = y/1 (dose of toxicant/IC50)slope for dose-response relationships. IC50 (+/- SEM) was estimated (P less than 0.05). An application with phosalone as a toxicant is presented.

Can the individual calibration be modified when laser fluorescence method is used for caries detection?

PubMed

Reyes, Alessandra; Ferreira, Gisele E; Santos, Joyce; Mendes, Fausto M; Imparato, Jose C P; Braga, Mariana M

2013-03-01

Individual calibration (IC) for caries detection methods based on fluorescence is time-consuming, especially for paediatric dentists, if the calibration has to be performed tooth-by-tooth. However, it is not clear how this calibration actually interfere in laser fluorescence (LF) readings. This in vivo study was to verify the influence of different modes of IC on laser fluorescence (LF) readings. Ninety six occlusal and 95 buccal surfaces of 1st permanent molars were examined using LF device after IC performed on control (no IC), the examined teeth, a permanent incisor, a 1st primary molar or a 2nd primary molar. All modes of IC were performed in the same child. Wilcoxon test and Bland-Altman analysis were used to compare the readings. Intraclass correlation coefficients (ICC) were calculated. Laser fluorescence readings without prior calibration were higher than readings performed after any mode of IC and resulted in different values of ICC. After other IC modes, the LF readings were statistically similar. The absence of IC influences LF readings and LF reproducibility, but different IC methods can be considered in clinical practice. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

Confirmation of gastric tube bedside placement with the sky blue method.

PubMed

Imamura, Takashi; Maeda, Hajime; Kinoshita, Hidetoshi; Shibukawa, Yasuko; Suda, Kiyomi; Fukuda, Yutaka; Goto, Aya; Nagasawa, Katsutoshi

2014-02-01

The purpose was to review our experiences and determine if applying the sky blue method is reliable in confirming gastric tube (GT) placement in neonates. The study population consisted of 44 infants (55 placements) who were admitted to the Takeda General Hospital between April 2012 and March 2013 and who required GT exchange. The sky blue method using indigo carmine (IC) was indicated for planned tube exchange only. Diluted IC was injected into the gastric space via the old GT just before the tube exchange. The tube was exchanged using a standard method. Then, we checked whether the diluted IC could be collected through the new GT or not. The reasons for GT placement were a gestational age of < 35 weeks in 31 (56.4%), poor sucking or swallowing disorders in 17 (30.4%), and respiratory disorders in 7 (12.7%) of the 55 placements. GT placement using the sky blue method was considered successful in 52 placements (94.4%), with the remaining 3 placements (5.6%) considered to be failures due to the inability to obtain IC from the gastric space. No adverse events were observed during the tube exchange period. Based on the results, the sky blue method can be considered to be reliable method for the confirmation of GT placement. These results also suggest that the number of radiologic evaluations performed to confirm correct replacement of the GT in infants can be reduced in the future.

Obstacles to care in first-episode psychosis patients with a long duration of untreated psychosis.

PubMed

Bay, Nina; Bjørnestad, Jone; Johannessen, Jan O; Larsen, Tor K; Joa, Inge

2016-02-01

This qualitative study is a sub-study of the early 'Treatment and Intervention in Psychosis Study' (TIPS-2), a program for early intervention strategies for people experiencing a first episode of psychosis. We aimed to improve knowledge about factors that prevent or delay patients with a long duration of psychosis from accessing psychiatric health-care services at an earlier illness stage and their personal views on the impact of ongoing informational campaigns (ICs) on help-seeking behaviour. Following an interpretative-phenomenological approach, eight consecutive TIPS-2 patients with duration of untreated psychosis lasting for more than 6 months were interviewed. The interviews were analysed using a meaning condensation procedure. Five main themes were identified: (i) participants' failure to recognize symptoms of psychosis; (ii) difficulties expressing their experiences; (iii) concerns about stigma; (iv) poor psychosis detection skills among health-care professionals; and (v) participants' lack of awareness or understanding of ICs. The five themes identified may suggest that despite exposure to the targeted ICs, participants were unable to recognize or understand the severity of their symptoms. Further, although family members or others sometimes recognized the initial symptoms of psychosis development, these symptoms were attributed to reasons other than psychosis. Participants reported that health-care personnel also had trouble identifying emerging signs of psychosis. The ICs need to be carefully crafted to relay information to people who do not consider themselves as currently experiencing signs of psychosis. © 2014 Wiley Publishing Asia Pty Ltd.

Sino-Canadian collaborations in stem cell research: a scientometric analysis.

PubMed

Ali-Khan, Sarah E; Ray, Monali; McMahon, Dominique S; Thorsteinsdóttir, Halla

2013-01-01

International collaboration (IC) is essential for the advance of stem cell research, a field characterized by marked asymmetries in knowledge and capacity between nations. China is emerging as a global leader in the stem cell field. However, knowledge on the extent and characteristics of IC in stem cell science, particularly China's collaboration with developed economies, is lacking. We provide a scientometric analysis of the China-Canada collaboration in stem cell research, placing this in the context of other leading producers in the field. We analyze stem cell research published from 2006 to 2010 from the Scopus database, using co-authored papers as a proxy for collaboration. We examine IC levels, collaboration preferences, scientific impact, the collaborating institutions in China and Canada, areas of mutual interest, and funding sources. Our analysis shows rapid global expansion of the field with 48% increase in papers from 2006 to 2010. China now ranks second globally after the United States. China has the lowest IC rate of countries examined, while Canada has one of the highest. China-Canada collaboration is rising steadily, more than doubling during 2006-2010. China-Canada collaboration enhances impact compared to papers authored solely by China-based researchers This difference remained significant even when comparing only papers published in English. While China is increasingly courted in IC by developed countries as a partner in stem cell research, it is clear that it has reached its status in the field largely through domestic publications. Nevertheless, IC enhances the impact of stem cell research in China, and in the field in general. This study establishes an objective baseline for comparison with future studies, setting the stage for in-depth exploration of the dynamics and genesis of IC in stem cell research.

Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

PubMed

Cerruto, M A; D'Elia, C; Siracusano, S; Gedeshi, X; Mariotto, A; Iafrate, M; Niero, M; Lonardi, C; Bassi, P; Belgrano, E; Imbimbo, C; Racioppi, M; Talamini, R; Ciciliato, S; Toffoli, L; Rizzo, M; Visalli, F; Verze, P; Artibani, W

2016-03-01

The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sino-Canadian Collaborations in Stem Cell Research: A Scientometric Analysis

PubMed Central

Ali-Khan, Sarah E.; Ray, Monali; McMahon, Dominique S.; Thorsteinsdóttir, Halla

2013-01-01

Background International collaboration (IC) is essential for the advance of stem cell research, a field characterized by marked asymmetries in knowledge and capacity between nations. China is emerging as a global leader in the stem cell field. However, knowledge on the extent and characteristics of IC in stem cell science, particularly China’s collaboration with developed economies, is lacking. Methods and Findings We provide a scientometric analysis of the China–Canada collaboration in stem cell research, placing this in the context of other leading producers in the field. We analyze stem cell research published from 2006 to 2010 from the Scopus database, using co-authored papers as a proxy for collaboration. We examine IC levels, collaboration preferences, scientific impact, the collaborating institutions in China and Canada, areas of mutual interest, and funding sources. Our analysis shows rapid global expansion of the field with 48% increase in papers from 2006 to 2010. China now ranks second globally after the United States. China has the lowest IC rate of countries examined, while Canada has one of the highest. China–Canada collaboration is rising steadily, more than doubling during 2006–2010. China–Canada collaboration enhances impact compared to papers authored solely by China-based researchers This difference remained significant even when comparing only papers published in English. Conclusions While China is increasingly courted in IC by developed countries as a partner in stem cell research, it is clear that it has reached its status in the field largely through domestic publications. Nevertheless, IC enhances the impact of stem cell research in China, and in the field in general. This study establishes an objective baseline for comparison with future studies, setting the stage for in-depth exploration of the dynamics and genesis of IC in stem cell research. PMID:23468927

Research on the exponential growth effect on network topology: Theoretical and empirical analysis

NASA Astrophysics Data System (ADS)

Li, Shouwei; You, Zongjun

Integrated circuit (IC) industry network has been built in Yangtze River Delta with the constant expansion of IC industry. The IC industry network grows exponentially with the establishment of new companies and the establishment of contacts with old firms. Based on preferential attachment and exponential growth, the paper presents the analytical results in which the vertices degree of scale-free network follows power-law distribution p(k)˜k‑γ (γ=2β+1) and parameter β satisfies 0.5≤β≤1. At the same time, we find that the preferential attachment takes place in a dynamic local world and the size of the dynamic local world is in direct proportion to the size of whole networks. The paper also gives the analytical results of no-preferential attachment and exponential growth on random networks. The computer simulated results of the model illustrate these analytical results. Through some investigations on the enterprises, this paper at first presents the distribution of IC industry, composition of industrial chain and service chain firstly. Then, the correlative network and its analysis of industrial chain and service chain are presented. The correlative analysis of the whole IC industry is also presented at the same time. Based on the theory of complex network, the analysis and comparison of industrial chain network and service chain network in Yangtze River Delta are provided in the paper.

Correlation between doctor's belief on the patient's self-determination and medical outcomes in obtaining informed consent.

PubMed

Yoshihara, Keisuke; Takase, Kozo

2013-03-01

We employed a questionnaire survey to assess attitudes toward informed consent (IC) among hospital doctors. Based on the result of the correlation analysis, the following two hypotheses were identified. The first hypothesis is that "the doctor's belief that the patient's self-determination is possible promotes cure of illness by obtaining IC." The second hypothesis is that "the doctor's belief that the patient's self-determination is possible has a positive influence on patient's quality of life by obtaining IC." We clarified the rationale for explaining these two hypotheses by applying cross tabulation analysis, discriminant analysis and principal component analysis (PCA). The doctors were divided into two groups in terms of their position on the patient's self-determination. One group of doctors believed the possibility of patient's self-determination, and the other did not. Through our statistical analyses, the characteristics that discriminate these two groups were identified. It was revealed that the former group placed a great importance on the hospitality value, while the latter placed an importance on the service value. Agreement or rejection of the concept of IC has been demonstrated as a key distinguishing factor between the two groups. The results of PCA showed that the doctor's belief on the patient's self-determination in obtaining IC had a significant effect on medical outcomes, and the two above-mentioned hypotheses were revealed.

Motor Recovery After Subcortical Stroke Depends on Modulation of Extant Motor Networks.

PubMed

Sharma, Nikhil; Baron, Jean-Claude

2015-01-01

Stroke is the leading cause of long-term disability. Functional imaging studies report widespread changes in movement-related cortical networks after stroke. Whether these are a result of stroke-specific cognitive processes or reflect modulation of existing movement-related networks is unknown. Understanding this distinction is critical in establishing more effective restorative therapies after stroke. Using multivariate analysis (tensor-independent component analysis - TICA), we map the neural networks involved during motor imagery (MI) and executed movement (EM) in subcortical stroke patients and age-matched controls. Twenty subcortical stroke patients and 17 age-matched controls were recruited. They were screened for their ability to carry out MI (Chaotic MI Assessment). The fMRI task was a right-hand finger-thumb opposition sequence (auditory-paced 1 Hz; 2, 3, 4, 5, 2…). Two separate runs were acquired (MI and rest and EM and rest; block design). There was no distinction between groups or tasks until the last stage of analysis, which allowed TICA to identify independent components (ICs) that were common or distinct to each group or task with no prior assumptions. TICA defined 28 ICs. ICs representing artifacts were excluded. ICs were only included if the subject scores were significant (for either EM or MI). Seven ICs remained that involved the primary and secondary motor networks. All ICs were shared between the stroke and age-matched controls. Five ICs were common to both tasks and three were exclusive to EM. Two ICs were related to motor recovery and one with time since stroke onset, but all were shared with age-matched controls. No IC was exclusive to stroke patients. We report that the cortical networks in stroke patients that relate to recovery of motor function represent modulation of existing cortical networks present in age-matched controls. The absence of cortical networks specific to stroke patients suggests that motor adaptation and other potential confounders (e.g., effort and additional muscle use) are not responsible for the changes in the cortical networks reported after stroke. This highlights that recovery of motor function after subcortical stroke involves preexisting cortical networks that could help identify more effective restorative therapies.

Useful Immunochromatographic Assay of Calprotectin in Gingival Crevicular Fluid for Diagnosis of Diseased Sites in Patients with Periodontal Diseases.

PubMed

Kido, Jun-Ichi; Murakami, Shinya; Kitamura, Masahiro; Yanagita, Manabu; Tabeta, Koichi; Yamazaki, Kazuhisa; Yoshie, Hiromasa; Watanabe, Hisashi; Izumi, Yuichi; Suda, Reiko; Yamamoto, Matsuo; Shiba, Hideki; Fujita, Tsuyoshi; Kurihara, Hidemi; Mizuno, Mitsuharu; Mishima, Akihiro; Kawahara, Nobumasa; Hashimoto, Kazuhiro; Naruishi, Koji; Nagata, Toshihiko

2017-09-06

Calprotectin, an inflammation-related protein, is present in gingival crevicular fluid (GCF) and the determination of calprotectin is useful for diagnosing periodontal diseases. We have recently developed a novel immunochromatographic (IC) chip system (SI-101402) to determine calprotectin levels in GCF. In the present study, the usefulness of this diagnostic system was investigated in patients with periodontal diseases. Thirty-six patients with periodontal diseases participated in this clinical test at multiple centers. Periodontitis sites (n=118) and non-periodontitis (healthy) sites (n=120) were selected after periodontal examination. GCF collection and periodontal examination were performed at baseline, after supragingival and subgingival scaling and root planing. Calprotectin amount in GCF was determined using a novel IC chip system and evaluated as a visual score and an IC reader value. The correlation between GCF calprotectin levels, clinical indicators and changes in calprotectin levels by periodontal treatments were investigated. Receiver operating characteristic (ROC) analysis of IC reader value for GCF calprotectin was performed to predict periodontal diseases. The visual score of GCF calprotectin was highly correlated the IC reader value. IC reader values of GCF calprotectin in periodontitis group were higher than those of healthy group at three dental examination stages and they significantly decreased with periodontal treatments. Visual scores and IC reader values of GCF calprotectin were correlated to the levels of clinical indicators. ROC analysis for GCF calprotectin showed an optimal cutoff value to predict periodontal diseases. Determination of GCF calprotectin using a novel IC chip system is useful for diagnosis of periodontal diseases.

Infectious complications after vehicular trauma in the United States.

PubMed

Fraser, Douglas R; Dombrovskiy, Viktor Y; Vogel, Todd R

2011-08-01

The purpose of this analysis was to evaluate and define the rates of infectious complications (IC) after vehicular trauma. Secondary goals were to identify the injuries associated with the greatest risk of nosocomial infection and to measure the utilization of hospital resources associated with IC and vehicular trauma. A secondary analysis of the Nationwide Inpatient Sample (2003-2007) was performed to classify major vehicular trauma injuries utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) Emergency (E) codes. The post-traumatic IC evaluated were pneumonia, urinary tract infection (UTI), sepsis, and surgical site infection (SSI). All data were analyzed by χ(2) analysis, multivariable logistic regression, and the Cochran-Armitage test for trends. A total of 784,037 vehicular trauma patients were identified (462,543 [59.0%] motor vehicle drivers, 142,283 [18.2%] motor vehicle passengers, 98,767 [12.6%] motorcyclists; 6,568 [<1%] motorcycle passengers, and 73,876 [9.4%] pedestrians). Of those sustaining injuries, 44,331 [5.7%] had post-traumatic IC. Pneumonia and UTI were most common after spinal cord injury (SCI), whereas sepsis and SSI were most common after colon injuries. After adjustment by age, sex, and co-morbidities, patients with SCI were 4.4 times as likely (95% confidence interval [CI] 4.20-4.63) and those with cranial injuries were 2.1 times as likely (95% CI 2.06-2.19) to develop IC as patients without these injuries. Secondary infection increased significantly the length of stay and hospital charges in all groups. Patients sustaining vehicular trauma in combination with SCI had the highest rate of IC. Infectious complications increased hospital resource utilization significantly after vehicular trauma. Future root-cause analysis of high-risk groups may decrease complications and hospital utilization.

Chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from Cymbopogon nardus L.

PubMed

Muhd Haffiz, J; Norhayati, I; Getha, K; Nor Azah, M A; Mohd Ilham, A; Lili Sahira, H; Roshan Jahn, M S; Muhd Syamil, A

2013-03-01

Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis.

Isolation of intact RNA from murine CD4+ T cells after intracellular cytokine staining and fluorescence-activated cell sorting.

PubMed

Kunnath-Velayudhan, Shajo; Porcelli, Steven A

2018-05-01

Intracellular cytokine staining (ICS) is a powerful method for identifying functionally distinct lymphocyte subsets, and for isolating these by fluorescence activated cell sorting (FACS). Although transcriptomic analysis of cells sorted on the basis of ICS has many potential applications, this is rarely performed because of the difficulty in isolating intact RNA from cells processed using standard fixation and permeabilization buffers for ICS. To address this issue, we compared three buffers shown previously to preserve RNA in nonhematopoietic cells subjected to intracellular staining for their effects on RNA isolated from T lymphocytes processed for ICS. Our results showed that buffers containing the recombinant ribonuclease inhibitor RNasin or high molar concentrations of salt yielded intact RNA from fixed and permeabilized T cells. As proof of principle, we successfully used the buffer containing RNasin to isolate intact RNA from CD4 + T cells that were sorted by FACS on the basis of specific cytokine production, thus demonstrating the potential of this approach for coupling ICS with transcriptomic analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

A Comparative Analysis of Computer End-User Support in the Air Force and Civilian Organizations

DTIC Science & Technology

1991-12-01

This explanation implies a further stratification of end users based on the specific tasks they perform, a new model of application combinations, and a...its support efforts to meet the needs of its end-uiser clientele iore closely. 79 INTEGRATED .9 VERBAL ANALYTIC Figure 14. Test Model of Applications ...The IC Model : IEM, Canada. ...............19 Proliferation of ICs ... ............... 20 Services ... ..................... 21 IC States

Application of ion chromatography in pharmaceutical and drug analysis.

PubMed

Jenke, Dennis

2011-08-01

Ion chromatography (IC) has developed and matured into an important analytical methodology in a number of diverse applications and industries, including pharmaceuticals. This manuscript provides a review of IC applications for the determinations of active and inactive ingredients, excipients, degradation products, and impurities relevant to pharmaceutical analyses and thus serves as a resource for investigators looking for insights into the use of the IC methodology in this field of application.

Acoustic evaluation of pirfenidone on patients with combined pulmonary fibrosis emphysema syndrome.

PubMed

Charleston-Villalobos, Sonia; Castaneda-Villa, Norma; Gonzalez-Camarena, Ramon; Mejia-Avila, M; Mateos-Toledo, H; Aljama-Corrales, Tomas

2016-08-01

The combined pulmonary fibrosis emphysema syndrome (CPFES) overall has a poor prognosis with a 5-year survival of 35-80%. Consequently, to evaluate possible positive effects on patients of novel agents as pirfenidone is relevant. However, the efficacy of pirfenidone in CPFES patients is still not well-known. In this study we propose an alternative to evaluate the effects of pirfenidone treatment on CPFES patients via acoustic information. Quantitative analysis of discontinuous adventitious lung sounds (DLS), known as crackles, has been promising to detect and characterize diverse pulmonary pathologies. The present study combines independent components (ICs) analysis of LS and the automated selection of ICs associated with DLS. ICs's features as fractal dimension, entropy and sparsity produce several clusters by kmeans. Those clusters containing ICs of DLS are exclusively considered to finally estimate the number of DLS per ICs by a time-variant AR modeling. For the evaluation of the effects of pirfenidone, the 2D DLS-ICs spatial distribution in conjunction with the estimated number of DLS events are shown. The methodology is applied to two real cases of CPFES with 6 and 12 months of treatment. The acoustical evaluation indicates that pirfenidone treatment may not be satisfactory for CPFES patients but further evaluation has to be performed.

Administrative claims analysis of asthma-related health care utilization for patients who received inhaled corticosteroids with either montelukast or salmeterol as combination therapy.

PubMed

Allen-Ramey, Felicia C; Bukstein, Don; Luskin, Allan; Sajjan, Shiva G; Markson, Leona E

2006-05-01

To compare asthma-related health care resource utilization among a matched cohort of asthma patients using inhaled corticosteroids (ICSs) plus either montelukast (MON) or salmeterol (SAL) as combination therapy for asthma, during a time prior to the availability of fixed-dose combinations of ICS/SAL. A retrospective analysis using the PHARMetrics patient-centric claims database was conducted for the period preceding the market introduction of combination fluticasone-SAL in September 2000. Patients had to meet the following criteria for inclusion in the study: they had to be between the ages of 4 and 55 years; they had to have been continuously enrolled for 2 years; they had to have initiated ICS/MON or ICS/SAL therapy between July 1, 1998, and June 30, 1999; and they had to have had either (a) a diagnosis of asthma (based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 493.xx) for 2 outpatient visits, 1 or more emergency department (ED) visits, or 1 or more hospitalizations within 1 year or (b) pharmacy claim records that contained a National Drug Code for an antiasthma medication (betaagonist, theophylline, ICS, cromolyn, or leukotriene) 2 or more times within 1 year. ICS/MON and ICS/SAL patients were matched 1 to 1 on age and propensity score. Outcomes included asthma-related hopitalizations and ED visits with ICD-9-CM codes of 493.xx, and oral corticosteroid (OCS) fills and short-acting beta-agonist (SABA) fills. Multivariate regression analyses were performed. Subgroup analyses based on sequential or concurrent initiation of combination therapy were also conducted. A total of 1,216 patients were matched (ICS/MON = 608; ICS/SAL= 608). Decreased odds of ED visits and/or hospitalizations were observed with ICS/MON (adjusted odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.35- 0.98) versus ICS/SAL. The odds of postindex OCS fills were not different for ICS/MON and ICS/SAL patients (adjusted OR = 1.04; 95% CI, 0.79-1.38). Postindex pharmacy claims for SABAs were significantly higher among ICS/MON patients versus ICS/SAL patients (adjusted relative risk [RR] = 1.33; 95% CI, 1.17-1.52), and this difference remained regardless of prior use or no prior use of ICSs. In subgroup analyses, mean change in SABA fills varied by how combination therapy was initiated, with sequential addition of asthma controllers leading to a reduction in SABA fills in both groups. For patients with concurrent initiation of combination therapy, the odds of ED visits/hospitalizations were significantly lower in patients initiating ICS/MON (adjusted OR = 0.25; 95% CI, 0.08-0.79). In this matched cohort, use of ICS/MON compared with ICS/SAL resulted in similar odds of OCS fills, decreased odds of ED visits and asthmarelated hospitalizations, but higher utilization of SABA.

bop5 mutations reveal new roles for the IC138 phosphoprotein in the regulation of flagellar motility and asymmetric waveforms

PubMed Central

VanderWaal, Kristyn E.; Yamamoto, Ryosuke; Wakabayashi, Ken-ichi; Fox, Laura; Kamiya, Ritsu; Dutcher, Susan K.; Bayly, Phillip V.; Sale, Winfield S.; Porter, Mary E.

2011-01-01

I1 dynein, or dynein f, is a highly conserved inner arm isoform that plays a key role in the regulation of flagellar motility. To understand how the IC138 IC/LC subcomplex modulates I1 activity, we characterized the molecular lesions and motility phenotypes of several bop5 alleles. bop5-3, bop5-4, and bop5-5 are null alleles, whereas bop5-6 is an intron mutation that reduces IC138 expression. I1 dynein assembles into the axoneme, but the IC138 IC/LC subcomplex is missing. bop5 strains, like other I1 mutants, swim forward with reduced swimming velocities and display an impaired reversal response during photoshock. Unlike mutants lacking the entire I1 dynein, however, bop5 strains exhibit normal phototaxis. bop5 defects are rescued by transformation with the wild-type IC138 gene. Analysis of flagellar waveforms reveals that loss of the IC138 subcomplex reduces shear amplitude, sliding velocities, and the speed of bend propagation in vivo, consistent with the reduction in microtubule sliding velocities observed in vitro. The results indicate that the IC138 IC/LC subcomplex is necessary to generate an efficient waveform for optimal motility, but it is not essential for phototaxis. These findings have significant implications for the mechanisms by which IC/LC complexes regulate dynein motor activity independent of effects on cargo binding or complex stability. PMID:21697502

Roadmap to Secure Control Systems in the Water Sector

DTIC Science & Technology

2008-03-01

solutions for ICS security. The purposes of this roadmap are as follows: • Define a consensus-based framework that articulates strategies of owners and...each failure is manageable in itself • Be used as ransomware 400,000 persons, and was estimated by the Center for Disease Control (CDC) to cost a total...and focused efforts. The water sector has developed and will pursue a set of strategic goals articulating these ambitions. These goals will help

Risk of pneumonia in obstructive lung disease: A real-life study comparing extra-fine and fine-particle inhaled corticosteroids.

PubMed

Sonnappa, Samatha; Martin, Richard; Israel, Elliot; Postma, Dirkje; van Aalderen, Wim; Burden, Annie; Usmani, Omar S; Price, David B

2017-01-01

Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD. The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used. Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS. The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose. To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used. 14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS. On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS. Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size. These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk.

Congenital disorder of glycosylation Ic due to a de novo deletion and an hALG-6 mutation.

PubMed

Eklund, Erik A; Sun, Liangwu; Yang, Samuel P; Pasion, Romela M; Thorland, Erik C; Freeze, Hudson H

2006-01-20

We describe a new cause of congenital disorder of glycosylation-Ic (CDG-Ic) in a young girl with a rather mild CDG phenotype. Her cells accumulated lipid-linked oligosaccharides lacking three glucose residues, and sequencing of the ALG6 gene showed what initially appeared to be a homozygous novel point mutation (338G>A). However, haplotype analysis showed that the patient does not carry any paternal DNA markers extending 33kb in the telomeric direction from the ALG6 region, and microsatellite analysis extended the abnormal region to at least 2.5Mb. We used high-resolution karyotyping to confirm a deletion (10-12Mb) [del(1)(p31.2p32.3)] and found no structural abnormalities in the father, suggesting a de novo event. Our findings extend the causes of CDG to larger DNA deletions and identify the first Japanese CDG-Ic mutation.

Irreducible incoherence and intelligent design: a look into the conceptual toolbox of a pseudoscience.

PubMed

Boudry, Maarten; Blancke, Stefaan; Braeckman, Johan

2010-12-01

The concept of Irreducible Complexity (IC) has played a pivotal role in the resurgence of the creationist movement over the past two decades. Evolutionary biologists and philosophers have unambiguously rejected the purported demonstration of "intelligent design" in nature, but there have been several, apparently contradictory, lines of criticism. We argue that this is in fact due to Michael Behe's own incoherent definition and use of IC. This paper offers an analysis of several equivocations inherent in the concept of Irreducible Complexity and discusses the way in which advocates of the Intelligent Design Creationism (IDC) have conveniently turned IC into a moving target. An analysis of these rhetorical strategies helps us to understand why IC has gained such prominence in the IDC movement, and why, despite its complete lack of scientific merits, it has even convinced some knowledgeable persons of the impending demise of evolutionary theory.

Alterations of microbiota in urine from women with interstitial cystitis

PubMed Central

2012-01-01

Background Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine. Results The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine. Conclusion The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease. PMID:22974186

Parental intermittent claudication as risk factor for claudication in adults.

PubMed

Prushik, Scott G; Farber, Alik; Gona, Philimon; Shrader, Peter; Pencina, Michael J; D'Agostino, Ralph B; Murabito, Joanne M

2012-03-01

Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased the risk of IC in adult offspring, independent of the established cardiovascular risk factors. We evaluated the Offspring Cohort Participants of the Framingham Heart Study who were ≥30 years old, cardiovascular disease free, and had both parents enrolled in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled proportional hazards regression analysis was used to examine whether the 12-year risk of incident IC in offspring participants was associated with parental IC, adjusting for age, gender, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. Of the 909 person-examinations in the parental IC history group and 5,397 person-examinations in the no-parental IC history group, there were 101 incident IC events (29 with parental IC history and 72 without a parental IC history) during follow-up. The age- and gender-adjusted 12-year cumulative incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74 to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a parental IC history. A parental history of IC significantly increased the risk of incident IC in the offspring (multivariable adjusted hazard ratio 1.81, 95% CI 1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In conclusion, IC in parents increases the risk of IC in adult offspring, independent of the established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of an automated analysis system for data from flow cytometric intracellular cytokine staining assays from clinical vaccine trials

PubMed Central

Shulman, Nick; Bellew, Matthew; Snelling, George; Carter, Donald; Huang, Yunda; Li, Hongli; Self, Steven G.; McElrath, M. Juliana; De Rosa, Stephen C.

2008-01-01

Background Intracellular cytokine staining (ICS) by multiparameter flow cytometry is one of the primary methods for determining T cell immunogenicity in HIV-1 clinical vaccine trials. Data analysis requires considerable expertise and time. The amount of data is quickly increasing as more and larger trials are performed, and thus there is a critical need for high throughput methods of data analysis. Methods A web based flow cytometric analysis system, LabKey Flow, was developed for analyses of data from standardized ICS assays. A gating template was created manually in commercially-available flow cytometric analysis software. Using this template, the system automatically compensated and analyzed all data sets. Quality control queries were designed to identify potentially incorrect sample collections. Results Comparison of the semi-automated analysis performed by LabKey Flow and the manual analysis performed using FlowJo software demonstrated excellent concordance (concordance correlation coefficient >0.990). Manual inspection of the analyses performed by LabKey Flow for 8-color ICS data files from several clinical vaccine trials indicates that template gates can appropriately be used for most data sets. Conclusions The semi-automated LabKey Flow analysis system can analyze accurately large ICS data files. Routine use of the system does not require specialized expertise. This high-throughput analysis will provide great utility for rapid evaluation of complex multiparameter flow cytometric measurements collected from large clinical trials. PMID:18615598

The association of ethnicity with electronically measured adherence to inhaled corticosteroids in children.

PubMed

Vasbinder, Erwin; Dahhan, Nordin; Wolf, Bart; Zoer, Jan; Blankman, Ellen; Bosman, Diederik; van Dijk, Liset; van den Bemt, Patricia

2013-03-01

To investigate the association of ethnicity with objectively, electronically measured adherence to inhaled corticosteroids (ICS) in a multicultural population of children with asthma in the city of Amsterdam. The study was designed as a prospective, observational multicenter study in which adherence to ICS and potential risk factors for adherence to ICS were measured in a cohort of Moroccan and native Dutch children with asthma. Electronic adherence measurements were performed for 3 months per patient using a Real Time Medication Monitoring (RTMM) system. Ethnicity and other potential risk factors, such as socio-economic status, asthma control and parental medication beliefs, were extracted from medical records or parent interviews. The association between adherence and ethnicity was analysed using multivariate linear regression analysis. A total of 90 children (aged 1-11 years) were included in the study and data of 87 children were used for analysis. Average adherence to ICS was 49.3 %. Native Dutch children showed higher adherence to ICS than Moroccan children (55.9 vs. 42.5 %, respectively; p = 0.044, univariate analysis). After correction for confounders (>3 annual visits to the paediatric outpatient clinic, regular use of a spacer during inhalation), the final regression model showed that ethnicity was independently associated with adherence (p = 0.028). In our Western European population of inner city children with asthma, poor adherence to ICS was a serious problem, and even somewhat more so in ethnic minorities. Paediatricians involved in asthma treatment should be aware of these cultural differences in medication-taking behaviour, but further studies are needed to elucidate the causal mechanism.

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

Li, Menglu; Tu, K. N., E-mail: kntu@ucla.edu; Kim, Dong Wook

Thermal-crosstalk induced thermomigration failure in un-powered microbumps has been found in 2.5D integrated circuit (IC) circuit. In 2.5D IC, a Si interposer was used between a polymer substrate and a device chip which has transistors. The interposer has no transistors. If transistors are added to the interposer chip, it becomes 3D IC. In our test structure, there are two Si chips placed horizontally on a Si interposer. The vertical connections between the interposer and the Si chips are through microbumps. We powered one daisy chain of the microbumps under one Si chip; however, the un-powered microbumps in the neighboring chipmore » are failed with big holes in the solder layer. We find that Joule heating from the powered microbumps is transferred horizontally to the bottom of the neighboring un-powered microbumps, and creates a large temperature gradient, in the order of 1000 °C/cm, through the un-powered microbumps in the neighboring chip, so the latter failed by thermomigration. In addition, we used synchrotron radiation tomography to compare three sets of microbumps in the test structure: microbumps under electromigration, microbumps under thermomigration, and microbumps under a constant temperature thermal annealing. The results show that the microbumps under thermomigration have the largest damage. Furthermore, simulation of temperature distribution in the test structure supports the finding of thermomigration.« less

Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.

PubMed

Wan, Guoxing; Tian, Lin; Yu, Yuandong; Li, Fang; Wang, Xuanbin; Li, Chen; Deng, Shouheng; Yu, Xiongjie; Cai, Xiaojun; Zuo, Zhigang; Cao, Fengjun

2017-09-09

The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

PubMed Central

Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

2008-01-01

Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Doe, Christine M; Humby, Trevor; Johnstone, Karen A; Resnick, James L; Holland, Anthony J; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2010-01-01

The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.

Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses.

PubMed

Schumann, Barbara; Winkler, Janine; Mickenautsch, Nicola; Warnken, Tobias; Dänicke, Sven

2016-08-01

Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and β-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC50 (μM) for DON, 3AcDON, β-ZEL, α-ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC50 values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 μM.The in vivo screening (N = 49) revealed the occurrence of ZEN (N = 24), α-ZEL (N = 3), β-ZEL (N = 37), DON, and DOM-1 (N = 2). The detected concentrations were much lower than the corresponding IC50 while the IC10 of DON and β-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of β-ZEL, α-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.

Impact of maternal obesity on inhaled corticosteroid use in childhood: a registry based analysis of first born children and a sibling pair analysis.

PubMed

Lowe, Adrian J; Ekeus, Cecilia; Bråbäck, Lennart; Rajaleid, Kristiina; Forsberg, Bertil; Hjern, Anders

2013-01-01

It has been proposed that maternal obesity during pregnancy may increase the risk that the child develops allergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought to assess if this association may be due to confounding by genetic or environmental risk factors that are common to maternal obesity and childhood asthma, using a sibling pair analysis. The study population comprised a Swedish national cohort of term children born between 1992 and 2008 to native Swedish parents. Maternal body mass index (BMI) was measured at 8-10 weeks gestation. Unconditional logistic regression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid (ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysis was performed, taking into account shared genetic and environmental risk factors. Maternal over-weight and obesity were associated with increased risk that the child would require ICS (for BMI≥35 kg/m(2), aOR = 1.30, 95%CI = 1.10-1.52 compared with normal weight mothers) in children aged 6-12 years. Similar effects were seen in younger children, but in children aged 13-16 years, maternal obesity (BMI≥30) was related to increased risk of ICS use in girls (aOR = 1.28, 95%CI = 1.07-1.53) but not boys (OR = 1.05, 95%CI = 0.87-1.26). The sib-pair analysis, which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failed to find any evidence that increasing maternal weight was related to increased risk of ICS use. Maternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, but only in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statistical power, or the effects of maternal BMI may be due to shared genetic or environmental risk factors.

Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma.

PubMed

Bacharier, Leonard B; Guilbert, Theresa W; Zeiger, Robert S; Strunk, Robert C; Morgan, Wayne J; Lemanske, Robert F; Moss, Mark; Szefler, Stanley J; Krawiec, Marzena; Boehmer, Susan; Mauger, David; Taussig, Lynn M; Martinez, Fernando D

2009-05-01

Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits. However, determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment. To determine if demographic and atopic features predict response to ICS in preschool children at high risk for asthma. Two years of treatment with an ICS, fluticasone propionate (88 microg twice daily), was compared with matching placebo in a double-masked, randomized, multicenter study of 285 children 2 and 3 years old at high risk for asthma development. Baseline demographic and atopic features were related to clinical outcomes in a post hoc subgroup analysis. Multivariate analysis demonstrated significantly greater improvement with fluticasone than placebo in terms of episode-free days among boys, white subjects, participants with an emergency department (ED) visit or hospitalization within the past year, and those who experienced more symptomatic days at baseline. Children with aeroallergen sensitization experienced greater benefits in terms of oral corticosteroid use, urgent care and ED visits, and use of supplemental controller medications. More favorable responses to ICS than placebo in high-risk preschool children over a 2-year period were more likely in those with a ED visit or hospitalization for asthma within the past year, children with aeroallergen sensitization, boys, and white subjects.

The relationship between perioperative administration of inhaled corticosteroid and postoperative respiratory complications after pulmonary resection for non-small-cell lung cancer in patients with chronic obstructive pulmonary disease.

PubMed

Yamanashi, Keiji; Marumo, Satoshi; Shoji, Tsuyoshi; Fukui, Takamasa; Sumitomo, Ryota; Otake, Yosuke; Sakuramoto, Minoru; Fukui, Motonari; Huang, Cheng-Long

2015-12-01

Inhaled corticosteroid (ICS) treatment has been shown to increase the risk of respiratory complications in patients with stable chronic obstructive pulmonary disease (COPD). However, the effects of perioperative ICS treatment on postoperative respiratory complications after lung cancer surgery have not been elucidated. The aim of this study was to investigate whether perioperative ICS treatment would increase the risk of postoperative respiratory complications after lung cancer surgery in patients with COPD. We retrospectively analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between January 2007 and December 2014. Subjects were grouped based on whether or not they were administered perioperative ICS treatment. Postoperative cardiopulmonary complications were compared between the groups. There were no statistically significant differences in the incidence of postoperative respiratory complications (P = 0.573) between the perioperative ICS treatment group (n = 16) and the control group (n = 158). Perioperative ICS treatment was not significantly associated with postoperative respiratory complications in the univariate or multivariate analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P = 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier analysis showed that there were no statistically significant differences in the postoperative respiratory complications-free durations between the groups (P = 0.566), even after propensity score matching (P = 0.551). There was no relationship between perioperative ICS administration and the incidences of postoperative respiratory complications after surgical resection for NSCLC in COPD patients.

Patients' characteristics informing practice: improving individualized nursing care in the radiation oncology setting.

PubMed

Rose, Pauline M

2018-05-04

A large number of patients attend for radiotherapy daily. Primary nurses in the study settings aim to individualize care for their patients. The individual characteristics of patients may determine their perceptions of nursing care, and provide guidance in tailoring their care. This study aimed to assess patients' personal characteristics on their perceptions of individualized care (IC) provided by nurses during a course of radiotherapy, and to determine predictor variables that may inform nursing practice. This cross-sectional, exploratory study was conducted in three radiotherapy departments in Australia. Patients (n = 250) completed the Individualized Care Scale_Patient (ICS_P). Data were analyzed using descriptive and inferential statistics, univariate analysis, and multiple regression analysis. Males reported significantly higher perceptions of IC than females in 7/9 subscales. Patients with head and neck and prostate cancer, as well as those requiring hospitalization during radiotherapy, scored significantly higher in 5/9 subscales. Courses > 30 days, those not receiving chemotherapy, and partnered patients reported greater IC across all subscales. Gender and hospitalization were the main predictor variables for IC. Patients reported moderately high levels of IC during their radiotherapy; however, standard demographic information may provide limited insight into improving care for the individual. Patient characteristics routinely chosen, such as age, gender, and education may not predict how patients perceive their care or support the tailoring of interventions to improve IC. Researching a range of related patient characteristics may prove a more useful concept for future nursing studies aiming to predict outcomes to tailor nursing practice.

Implementation of Change (IC).

DTIC Science & Technology

1980-06-30

4- co C\\J t ) t r) - 1 )C CC :r E 4-’ c) C- co cn a, ko r- co0 :3 -~ a)~ -D V) 0:3 4-2 CAA-SR-80-5 4-5. SUMMARY. The above discussion suggests that...MTOE documents frequently cost the Army resources; e.g., changes to components of sets, kits and outfits ( SKO ). On the other hand, failure to implement...either retraineo tn recruited to meet the qudlification requiremient. F-13 CAA-SR- KO -5 a. Central Assignment Procedures System (CAP III). Personnel

End User Acceptance - Requirements or Specifications, Certification, Testing

NASA Technical Reports Server (NTRS)

Jeevarajan, Judith

2013-01-01

NASA follows top level safety requirement of two-failure tolerance (t hree levels of controls or design for minimum risk) to all catastroph ic hazards in the design of safe li-ion batteries for space use. ? R igorous development testing at appropriate levels to credible offnominal conditions and review of test data. ? Implement robust design con trols based on test results and test again to confirm safety at the a ppropriate levels. ? Stringent testing of all (100%) flight batteries (from button cells to large batteries).

Does motor imagery share neural networks with executed movement: a multivariate fMRI analysis

PubMed Central

Sharma, Nikhil; Baron, Jean-Claude

2013-01-01

Introduction: Motor imagery (MI) is the mental rehearsal of a motor first person action-representation. There is interest in using MI to access the motor network after stroke. Conventional fMRI modeling has shown that MI and executed movement (EM) activate similar cortical areas but it remains unknown whether they share cortical networks. Proving this is central to using MI to access the motor network and as a form of motor training. Here we use multivariate analysis (tensor independent component analysis-TICA) to map the array of neural networks involved during MI and EM. Methods: Fifteen right-handed healthy volunteers (mean-age 28.4 years) were recruited and screened for their ability to carry out MI (Chaotic MI Assessment). fMRI consisted of an auditory-paced (1 Hz) right hand finger-thumb opposition sequence (2,3,4,5; 2…) with two separate runs acquired (MI & rest and EM & rest: block design). No distinction was made between MI and EM until the final stage of processing. This allowed TICA to identify independent-components (IC) that are common or distinct to both tasks with no prior assumptions. Results: TICA defined 52 ICs. Non-significant ICs and those representing artifact were excluded. Components in which the subject scores were significantly different to zero (for either EM or MI) were included. Seven IC remained. There were IC's shared between EM and MI involving the contralateral BA4, PMd, parietal areas and SMA. IC's exclusive to EM involved the contralateral BA4, S1 and ipsilateral cerebellum whereas the IC related exclusively to MI involved ipsilateral BA4 and PMd. Conclusion: In addition to networks specific to each task indicating a degree of independence, we formally demonstrate here for the first time that MI and EM share cortical networks. This significantly strengthens the rationale for using MI to access the motor networks, but the results also highlight important differences. PMID:24062666

Improved thermal stability of polylactic acid (PLA) composite film via PLA-β-cyclodextrin-inclusion complex systems.

PubMed

Byun, Youngjae; Rodriguez, Katia; Han, Jung H; Kim, Young Teck

2015-11-01

The effects of the incorporation of PLA-β-cyclodextrin-inclusion complex (IC) and β-cyclodextrin (β-CD) on biopolyester PLA films were investigated. Thermal stability, surface morphology, barrier, and mechanical properties of the films were measured at varying IC (1, 3, 5, and 7%) and β-CD (1 and 5%) concentrations. The PLA-IC-composite films (IC-PLA-CFs) showed uniform morphological structure, while samples containing β-CD (β-CD-PLA-CFs) showed high agglomeration of β-CD due to poor interfacial interaction between β-CD and PLA moieties. According to the thermal property analysis, the 5% IC-PLA-CFs showed 6.6 times lower dimensional changes (6.5%) at the temperature range of 20-80°C than that of pure PLA film (43.0%). The increase of IC or β-CD content in the PLA-composite films shifted the glass transition and crystallization temperature to higher temperature regions. The crystallinity of both composite films improved by increasing IC or β-CD content. Both composite films had higher oxygen and water vapor permeability as IC or β-CD content increased in comparison to pure PLA film. All the composite films had less flexibility and lower tensile strength than the pure PLA film. In conclusion, this study shows that the IC technique is valuable to improve the thermal expansion stability of PLA-based films. Published by Elsevier B.V.

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

PubMed Central

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

A Concept Analysis of Patient Participation in Intermediate Care.

PubMed

Kvæl, Linda Aimée Hartford; Debesay, Jonas; Langaas, Anne; Bye, Asta; Bergland, Astrid

2018-03-05

Although the concept of patient participation has been discussed for a number of years, there is still no clear definition of what constitutes the multidimensional concept, and the application of the concept in an intermediate care (IC) context lacks clarity. Therefore this paper seeks to identify and explore the attributes of the concept, to elaborate ways of understanding the concept of patient participation for geriatric patients in the context of IC. Walker and Avant's model of Concept analysis [1] based on a literature review. Patient participation in the context of IC can be defined as a dynamic process emphasizing the person as a whole, focusing on the establishment of multiple alliances that facilitate individualized information and knowledge exchange, and ensuring a reciprocal engagement in activities within flexible and interactive/dynamic organizational structures. Patient participation in IC means involving patients and their relatives in holistic interdisciplinary collaborative decision-making. The results highlight the complexity of patient participation and contribute to a greater understanding of the influence of organizational structure and management. The present study may provide a practical framework for researchers, policy makers and health professionals to facilitate patient participation in IC services. Copyright © 2018 Elsevier B.V. All rights reserved.

Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study.

PubMed

Ohyama, Kaname; Yoshimi, Haruka; Aibara, Nozomi; Nakamura, Yoichi; Miyata, Yasuyoshi; Sakai, Hideki; Fujita, Fumihiko; Imaizumi, Yoshitaka; Chauhan, Anil K; Kishikawa, Naoya; Kuroda, Naotaka

2017-01-15

Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., "focused cancer immunotherapy") based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n = 28), colon (n = 20), bladder (n = 20), renal cell (n = 15) and malignant lymphoma (n = 9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter-alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients. © 2016 UICC.

ToF-SIMS and principal component analysis of lipids and amino acids from inflamed and dysplastic human colonic mucosa.

PubMed

Urbini, Marco; Petito, Valentina; de Notaristefani, Francesco; Scaldaferri, Franco; Gasbarrini, Antonio; Tortora, Luca

2017-10-01

Here, time of flight secondary ion mass spectrometry (ToF-SIMS) and multivariate analysis were combined to study the role of ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), in the colon cancer progression. ToF-SIMS was used to obtain mass spectra and chemical maps from the mucosal surface of human normal (NC), inflamed (IC), and dysplastic (DC) colon tissues. Chemical mapping with a lateral resolution of ≈ 1 μm allowed to evaluate zonation of fatty acids and amino acids as well as the morphological condition of the intestinal glands. High mass resolution ToF-SIMS spectra showed chemical differences in lipid and amino acid composition as a function of pathological state. In positive ion mode, mono- (MAG), di- (DAG), and triacylglycerol (TAG) signals were detected in NC tissues, while in IC and DC tissues, the only cholesterol was present as lipid class representative. Signals from fatty acids, collected in negative ion mode, were subjected to principal component analysis (PCA). PCA showed a strict correlation between IC and DC samples, due to an increase of stearic, arachidonic, and linoleic acid. In the same way, differences in the amino acid composition were highlighted through multivariate analysis. PCA revealed that glutamic acid, leucine/isoleucine, and valine fragments are related to IC tissues. On the other hand, tyrosine, methionine, and tryptophan peaks contributed highly to the separation of DC tissues. Finally, a classification of NC, IC, and DC patients was also achieved through hierarchical cluster analysis of amino acid fragments. In this case, human colonic inflammation showed a stronger relationship with normal than dysplastic condition. Graphical Abstract ᅟ.

Ion chromatography for the precise analysis of chloride and sodium in sweat for the diagnosis of cystic fibrosis.

PubMed

Doorn, J; Storteboom, T T R; Mulder, A M; de Jong, W H A; Rottier, B L; Kema, I P

2015-07-01

Measurement of chloride in sweat is an essential part of the diagnostic algorithm for cystic fibrosis. The lack in sensitivity and reproducibility of current methods led us to develop an ion chromatography/high-performance liquid chromatography (IC/HPLC) method, suitable for the analysis of both chloride and sodium in small volumes of sweat. Precision, linearity and limit of detection of an in-house developed IC/HPLC method were established. Method comparison between the newly developed IC/HPLC method and the traditional Chlorocounter was performed, and trueness was determined using Passing Bablok method comparison with external quality assurance material (Royal College of Pathologists of Australasia). Precision and linearity fulfill criteria as established by UK guidelines are comparable with inductively coupled plasma-mass spectrometry methods. Passing Bablok analysis demonstrated excellent correlation between IC/HPLC measurements and external quality assessment target values, for both chloride and sodium. With a limit of quantitation of 0.95 mmol/L, our method is suitable for the analysis of small amounts of sweat and can thus be used in combination with the Macroduct collection system. Although a chromatographic application results in a somewhat more expensive test compared to a Chlorocounter test, more accurate measurements are achieved. In addition, simultaneous measurements of sodium concentrations will result in better detection of false positives, less test repeating and thus faster and more accurate and effective diagnosis. The described IC/HPLC method, therefore, provides a precise, relatively cheap and easy-to-handle application for the analysis of both chloride and sodium in sweat. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Dihydroartemisinin–piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study

PubMed Central

Amaratunga, Chanaki; Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Mao, Sivanna; Sopha, Chantha; Sam, Baramey; Dek, Dalin; Try, Vorleak; Amato, Roberto; Blessborn, Daniel; Song, Lijiang; Tullo, Gregory S; Fay, Michael P; Anderson, Jennifer M; Tarning, Joel; Fairhurst, Rick M

2016-01-01

Background Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin–piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia. Methods In this prospective cohort study, we enrolled patients aged 2–65 years with uncomplicated P falciparum malaria in three Cambodian provinces: Pursat, Preah Vihear, and Ratanakiri. Participants were given standard 3-day courses of dihydroartemisinin–piperaquine. Peripheral blood parasite densities were measured until parasites cleared and then weekly to 63 days. The primary outcome was recrudescent P falciparum parasitaemia within 63 days. We measured piperaquine plasma concentrations at baseline, 7 days, and day of recrudescence. We assessed phenotypic and genotypic markers of drug resistance in parasite isolates. The study is registered with ClinicalTrials.gov, number NCT01736319. Findings Between Sept 4, 2012, and Dec 31, 2013, we enrolled 241 participants. In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did. Patients with recrudescent P falciparum infections were more likely to have detectable piperaquine plasma concentrations at baseline compared with non-recrudescent patients, but did not differ significantly in age, initial parasite density, or piperaquine plasma concentrations at 7 days. Recrudescent parasites had a higher prevalence of kelch13 mutations, higher piperaquine 50% inhibitory concentration (IC50) values, and lower mefloquine IC50 values; none had multiple pfmdr1 copies, a genetic marker of mefloquine resistance. Interpretation Dihydroartemisinin–piperaquine failures are caused by both artemisinin and piperaquine resistance, and commonly occur in places where dihydroartemisinin–piperaquine has been used in the private sector. In Cambodia, artesunate plus mefloquine may be a viable option to treat dihydroartemisinin–piperaquine failures, and a more effective first-line ACT in areas where dihydroartemisinin–piperaquine failures are common. The use of single low-dose primaquine to eliminate circulating gametocytes is needed in areas where artemisinin and ACT resistance is prevalent. Funding National Institute of Allergy and Infectious Diseases. PMID:26774243

Water-soluble polysaccharides from agro-industrial by-products: functional and biological properties.

PubMed

Sila, Assaâd; Bayar, Nadia; Ghazala, Imen; Bougatef, Ali; Ellouz-Ghorbel, Raoudha; Ellouz-Chaabouni, Semia

2014-08-01

Water-soluble polysaccharides were isolated from almond (AWSP) and pistachio (PWSP) juice processing by-products. Their chemical and physical characteristics were determined using NMR and Infrared spectroscopic analysis. The complexities of the spectra reflected the heterogeneity of these polysaccharides. The ACE inhibitory activities (IC50 AWSP=2.81mgmL(-1) and IC50 PWSP=2.59mgmL(-1)) and antioxidant properties of AWSP and PWSP were investigated based on the DPPH radical-scavenging capacity assay (IC50 AWSP=2.87mgmL(-1) and IC50 PWSP=1.61mgmL(-1)). Reducing power, β-carotene bleaching inhibition (IC50AWSP=4.46mgmL(-1) and IC50 PWSP=3.39mgmL(-1)), and ferrous chelating assays (IC50 AWSP=0.22mgmL(-1) and IC50 PWSP=0.19mgmL(-1)) were also performed. The findings revealed that water-soluble polysaccharides exhibited antioxidant and antihypertensive activities. AWSP and PWSP showed excellent interfacial concentration-dependent properties. Overall, the results suggested that both AWSP and PWSP are promising sources of natural antioxidants and ACE inhibitory agents and could, therefore, be used as alternative additives in food, pharmaceutical and cosmetic preparations. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis and development of adjoint-based h-adaptive direct discontinuous Galerkin method for the compressible Navier-Stokes equations

NASA Astrophysics Data System (ADS)

Cheng, Jian; Yue, Huiqiang; Yu, Shengjiao; Liu, Tiegang

2018-06-01

In this paper, an adjoint-based high-order h-adaptive direct discontinuous Galerkin method is developed and analyzed for the two dimensional steady state compressible Navier-Stokes equations. Particular emphasis is devoted to the analysis of the adjoint consistency for three different direct discontinuous Galerkin discretizations: including the original direct discontinuous Galerkin method (DDG), the direct discontinuous Galerkin method with interface correction (DDG(IC)) and the symmetric direct discontinuous Galerkin method (SDDG). Theoretical analysis shows the extra interface correction term adopted in the DDG(IC) method and the SDDG method plays a key role in preserving the adjoint consistency. To be specific, for the model problem considered in this work, we prove that the original DDG method is not adjoint consistent, while the DDG(IC) method and the SDDG method can be adjoint consistent with appropriate treatment of boundary conditions and correct modifications towards the underlying output functionals. The performance of those three DDG methods is carefully investigated and evaluated through typical test cases. Based on the theoretical analysis, an adjoint-based h-adaptive DDG(IC) method is further developed and evaluated, numerical experiment shows its potential in the applications of adjoint-based adaptation for simulating compressible flows.

Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection.

PubMed

Wessels, Uwe; Zadak, Markus; Reiser, Astrid; Brockhaus, Janis; Ritter, Mirko; Abdolzade-Bavil, Afsaneh; Heinrich, Julia; Stubenrauch, Kay

2018-04-11

High drug concentrations in ocular fluids after intravitreal administration preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is therefore desirable for immunogenicity testing in ophthalmology. Immune complex (IC) antidrug antibody (ADA) assays were established for two species. The assays were compared with the bridging assay in ocular and plasma samples from two preclinical studies. The IC assays showed high drug tolerance, which enabled a reliable ADA detection in ocular fluids after intravitreal administration. The IC assays were superior to the bridging assay in the analysis of ocular fluids with high drug concentrations. The IC assay allows a reliable ADA detection in matrices with high drug concentrations, such as ocular fluids.

Fracture mechanics analysis of the dentine-luting cement interface.

PubMed

Ryan, A K; Mitchell, C A; Orr, J F

2002-01-01

The objectives of this study were to determine the fracture toughness of adhesive interfaces between dentine and clinically relevant, thin layers of dental luting cements. Cements tested included a conventional glass-ionomer, F (Fuji 1), a resin-modified glass-ionomer, FP (Fuji Plus) and a compomer cement, D (DyractCem). Ten miniature short-bar chevron notch specimens were manufactured for each cement, each comprising a 40 microm thick chevron of lute, between two 1.5 mm thick blocks of bovine dentine, encased in resin composite. The interfacial K(IC) results (MN/m3/2) were median (range): F; 0.152 (0.14-0.16), FP; 0.306 (0.27-0.37), D; 0.351 (0.31-0.37). Non-parametric statistical analysis showed that the fracture toughness of F was significantly lower (p <0.05) than those of FP or D, and all were significantly lower than values for monolithic cement specimens. Scanning electron microscopy of the specimens suggested crack propagation along the interface. However, energy dispersive X-ray analysis indicated that failure was cohesive within the cement. It is concluded that the fracture toughness of luting cement was lowered by cement-dentine interactions.

[Adherence to pharmaceutical guidance in patients over 85 years of age with chronic heart failure-stage C. Effects on 12-month mortality].

PubMed

Esteve Arríen, Ainhoa; Domínguez de Pablos, Gema; Minaya Saiz, Jesús

2009-01-01

To describe factors related to prescription on discharge of treatment for Chronic Heart Failure(CHF)-Stage C and to analyse whether this is related to 12month-mortality. Observational follow-up study of patients over 85 hospitalized during 2006/7 with Stage C-Chronic Heart Failure in an outskirt support hospital. Drug-prescription adherence was assessed according to the American Heart Society 2005-Guidelines and recommendations of the American Geriatrics Society-2007. A multivariate analysis of logistic regression was performed to obtain odds for 12-month mortality for each recommended therapy, adjusting by mortality risk factors. 104 patients aged 90+/-3yr were followed on discharge, 85% of which were women. NYHA-classes were distributed NYHA I-28,2%, II-37,9%, III-30,1%, IV-3,9%. Most frequently prescribed drugs were loop diuretics (83,3%) and IACEs/ARB (62%), and the less frequent beta-blockers (19,1%). IACEs/ARB were prescribed to those with lower functional impairment (p=0.04), and beta-blockers to those with worse NYHA class (p=0.02). All recommended prescriptions had a tendency to 12 month mortality risk reduction, even adjusted by age, functional status, co-morbidity, NYHA class and co-morbid atrial fibrillation, except for spironolactone (OR-1,8; IC95% 0,48-17,19). Treatment with CHF disease-modifying therapies except for spironolactone can reduce 12 month risk mortality, also in the oldest old. There exists room for improvement in frequency of drug prescription in this group of age.

SN2005da: A Spectroscopic and Photometric Analysis of a Peculiar Type Ic Supernova

NASA Astrophysics Data System (ADS)

Williamson, Jacob

2017-12-01

Core collapse supernovae are an important class of objects in stellar evolution research as they are the final life stage of high mass stars. Supernovae in general are classified into several spectral types; this paper explores SN 2005da, classified as a Type Ic, meaning it lacks hydrogen and helium lines. The supernova was originally classified as a broad-lined Type Ic (Type Ic-BL), with expansion velocities near maximum light greater than or approximately equal to 15000 km/s. However, some of the elements present in the spectrum, namely carbon and oxygen, have narrower lines (FWHM approximately equal to 2300 km/s) than other elements, indicating an interaction with a previously ejected envelope. The supernova is also found to have a decay time, with a change in magnitude over 15 days following maximum light of about 1.4 magnitudes, that is significantly faster than typical Type Ic or Ic-BL. This is more akin to a rarer object type known as a Type Ibn, although it lacks the characteristic narrow helium lines of this type. Therefore, SN 2005da appears to be unlike known examples of Type Ic supernovae.

Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma.

PubMed

Ramani, Meghana; Mudge, Miranda C; Morris, R Tyler; Zhang, Yuntao; Warcholek, Stanislaw A; Hurst, Miranda N; Riviere, Jim E; DeLong, Robert K

2017-03-06

There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (K b = 1.6-2.8 g -1 L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC-ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-γ. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma.

Translating infection control guidelines into practice: implementation process within a health care institution.

PubMed

Raveis, Victoria H; Conway, Laurie J; Uchida, Mayuko; Pogorzelska-Maziarz, Monika; Larson, Elaine L; Stone, Patricia W

2014-04-01

Health-care-associated infections (HAIs) remain a major patient safety problem even as policy and programmatic efforts designed to reduce HAIs have increased. Although information on implementing effective infection control (IC) efforts has steadily grown, knowledge gaps remain regarding the organizational elements that improve bedside practice and accommodate variations in clinical care settings. We conducted in-depth, semistructured interviews in 11 hospitals across the United States with a range of hospital personnel involved in IC (n = 116). We examined the collective nature of IC and the organizational elements that can enable disparate groups to work together to prevent HAIs. Our content analysis of participants' narratives yielded a rich description of the organizational process of implementing adherence to IC. Findings document the dynamic, fluid, interactional, and reactive nature of this process. Three themes emerged: implementing adherence efforts institution-wide, promoting an institutional culture to sustain adherence, and contending with opposition to the IC mandate.

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal dysfunction patients had 8.5-fold increased risk for adverse outcomes. Although IC is often self-limited, our data warrants special attention and aggressive therapy in treating these patients.

Resting energy expenditure per lean body mass determined by indirect calorimetry and bioelectrical impedance analysis in cats.

PubMed

Center, S A; Warner, K L; Randolph, J F; Wakshlag, J J; Sunvold, G D

2011-01-01

Resting energy expenditure (REE) approximates ≥60% of daily energy expenditure (DEE). Accurate REE determination could facilitate sequential comparisons among patients and diseases if normalized against lean body mass (LBM). (1) Validate open-flow indirect calorimetry (IC) system and multifrequency bioelectrical impedance analysis (MF-BIA) to determine REE and LBM, respectively, in healthy nonsedated cats of varied body conditions; (2) normalize REE against LBM. Fifty-seven adult neutered domestic short-haired cats with stable BW. Continuous (45-min) IC-measurements determined least observed metabolism REE. Cage gas flow regulated with mass flow controllers was verified using nitrogen dilution; span gases calibrated gas measurements. Respiratory quotient accuracy was verified using alcohol combustion. IC-REE was compared to DEE, determined using doubly labeled water. MF-BIA LBM was validated against criterion references (deuterium, sodium bromide). Intra- and interassay variation was determined for IC and MF-BIA. Mean IC-REE (175 ± 38.7 kcal; 1.5-14% intra- and interassay CV%) represented 61 ± 14.3% of DEE. Best MF-BIA measurements were collected in sternal recumbency and with electrodes in neck-tail configuration. MF-BIA LBM was not significantly different from criterion references and generated LBM interassay CV% of 6.6-10.1%. Over- and underconditioned cats had significantly (P ≤ .05) lower and higher IC-REE (kcal/kg) respectively, compared with normal-conditioned cats. However, differences resolved with REE/LBM (approximating 53 ± 10.3 kcal/LBM [kg]). IC and MF-BIA validated herein reasonably estimate REE and LBM in cats. REE/LBM(kg) may permit comparison of energy utilization in sequential studies or among different cats. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Development and Validation of a Portable and Inexpensive Tool to Measure the Drop Vertical Jump Using the Microsoft Kinect V2.

PubMed

Gray, Aaron D; Willis, Brad W; Skubic, Marjorie; Huo, Zhiyu; Razu, Swithin; Sherman, Seth L; Guess, Trent M; Jahandar, Amirhossein; Gulbrandsen, Trevor R; Miller, Scott; Siesener, Nathan J

Noncontact anterior cruciate ligament (ACL) injury in adolescent female athletes is an increasing problem. The knee-ankle separation ratio (KASR), calculated at initial contact (IC) and peak flexion (PF) during the drop vertical jump (DVJ), is a measure of dynamic knee valgus. The Microsoft Kinect V2 has shown promise as a reliable and valid marker-less motion capture device. The Kinect V2 will demonstrate good to excellent correlation between KASR results at IC and PF during the DVJ, as compared with a "gold standard" Vicon motion analysis system. Descriptive laboratory study. Level 2. Thirty-eight healthy volunteer subjects (20 male, 18 female) performed 5 DVJ trials, simultaneously measured by a Vicon MX-T40S system, 2 AMTI force platforms, and a Kinect V2 with customized software. A total of 190 jumps were completed. The KASR was calculated at IC and PF during the DVJ. The intraclass correlation coefficient (ICC) assessed the degree of KASR agreement between the Kinect and Vicon systems. The ICCs of the Kinect V2 and Vicon KASR at IC and PF were 0.84 and 0.95, respectively, showing excellent agreement between the 2 measures. The Kinect V2 successfully identified the KASR at PF and IC frames in 182 of 190 trials, demonstrating 95.8% reliability. The Kinect V2 demonstrated excellent ICC of the KASR at IC and PF during the DVJ when compared with the Vicon system. A customized Kinect V2 software program demonstrated good reliability in identifying the KASR at IC and PF during the DVJ. Reliable, valid, inexpensive, and efficient screening tools may improve the accessibility of motion analysis assessment of adolescent female athletes.

Screening of (-SEA) α-thalassaemia using an immunochromatographic strip assay for the ζ-globin chain in a population with a high prevalence and heterogeneity of haemoglobinopathies.

PubMed

Jomoui, Wittaya; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan; Fucharoen, Supan

2017-01-01

The presence of the ζ-globin chain is a good marker of (-- SEA ) α 0 -thalassaemia. We evaluated an immunochromatographic (IC) strip assay for ζ-globin in screening for (-- SEA ) α 0 -thalassaemia in a population with a high prevalence and heterogeneity of haemoglobinopathies. The study was carried out on 300 screen positive blood samples of Thai individuals. The IC strip assay for the ζ-globin chain was performed on all samples. The results were interpreted with thalassaemia genotyping using standard haemoglobin and DNA analyses. Several thalassaemia genotypes were noted. Among the 300 subjects investigated, 79 had a positive IC strip assay for ζ-globin and (-- SEA ) α 0 -thalassaemia was identified in 40 of them. No (-- SEA ) α 0 -thalassaemia was detected in the remaining 39 samples with a positive IC strip test result or in the 221 samples with a negative IC strip test result. Further DNA analysis identified α + -thalassaemia in 25 of the 39 (-- SEA ) α 0 -thalassaemia negative samples. Using this IC strip assay in combination with a conventional screening protocol for (-- SEA ) α 0 -thalassaemia could provide sensitivity and specificity of 100% and 90.4%, respectively. IC strip assay for ζ-globin is simple, rapid and does not require sophisticated equipment. Use of this test in addition to the existing screening protocol could detect potential (-- SEA ) α 0 -thalassaemia leading to a significant reduction in the workload of DNA analysis. This could be used in areas where haemoglobinopathies are prevalent and heterogeneous but molecular testing is not available. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

ANALYSIS OF ELECTROLESS NICKEL SOLUTIONS BY ANION CHROMATOGRAPHY

EPA Science Inventory

The principal appeal of ion chromatography (IC) as analytical technique lies in the ability to rapidly analyze a mixture of ions of widely varying concentrations and properties in a single elution. It is therefore not surprising that IC has been hampered by the similar ion exchan...

Separation and quantitation of plant and insect carbohydrate isomers found on the surface of cotton

USDA-ARS?s Scientific Manuscript database

Cotton stickiness researchers have worked to create ion chromatography (IC) carbohydrate separation methods which allow for minimal analysis time and reduced operational costs. Researchers have also tried to correlate scientifically backed IC data with the available physical stickiness tests, such ...

Cardiovascular mortality in patients with prostate cancer exposed to androgen deprivation therapy.

PubMed

Monzó-Gardiner, J I; Herranz-Amo, F

2015-10-01

A relationship between the administration of GnRH agonists and the risk of acute myocardial infarction (AMC) in patients with prostate cancer has been showed in the third observational study published in April 2014. The association AMC-orchiectomy was not found in any of these studies. Define risk factors for cardiovascular disease in patients treated with GnRH agonist. Their probable underlying pathogenic mechanism in the myocardium and peripheral vascular tree was also analyzed. English articles cited in PubMed were reviewed. No time period is specified. The last search date was 11/30/14. In patients with coronary history of AMC or congestive heart failure, hormonal neoadjuvant therapy increased cardiovascular mortality rates (HR: 1.96, IC 95%: 1.04-3.71; P=.04) as well as cardiovascular-specific mortality rates (AHR: 3.28; IC 95%: 1.01-10.64; P=.048). Two possible mechanisms can be involved: a) direct mechanism through myocardial receptor for GnRH/PKA along with atherogenic plaques; and b) indirect mechanism related with metabolic disturbances. Patients with AMC or congestive heart failure history could present a higher risk of death related to the use of GnRH agonists. In these cases, should carefully consider appropriateness of such treatment. These effects can explained by a direct mechanism on myocardium and peripheral vascular tree and indirect ones related with modified metabolic syndrome. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Review of methods for handling confounding by cluster and informative cluster size in clustered data

PubMed Central

Seaman, Shaun; Pavlou, Menelaos; Copas, Andrew

2014-01-01

Clustered data are common in medical research. Typically, one is interested in a regression model for the association between an outcome and covariates. Two complications that can arise when analysing clustered data are informative cluster size (ICS) and confounding by cluster (CBC). ICS and CBC mean that the outcome of a member given its covariates is associated with, respectively, the number of members in the cluster and the covariate values of other members in the cluster. Standard generalised linear mixed models for cluster-specific inference and standard generalised estimating equations for population-average inference assume, in general, the absence of ICS and CBC. Modifications of these approaches have been proposed to account for CBC or ICS. This article is a review of these methods. We express their assumptions in a common format, thus providing greater clarity about the assumptions that methods proposed for handling CBC make about ICS and vice versa, and about when different methods can be used in practice. We report relative efficiencies of methods where available, describe how methods are related, identify a previously unreported equivalence between two key methods, and propose some simple additional methods. Unnecessarily using a method that allows for ICS/CBC has an efficiency cost when ICS and CBC are absent. We review tools for identifying ICS/CBC. A strategy for analysis when CBC and ICS are suspected is demonstrated by examining the association between socio-economic deprivation and preterm neonatal death in Scotland. PMID:25087978

Auditory and visual interactions between the superior and inferior colliculi in the ferret.

PubMed

Stitt, Iain; Galindo-Leon, Edgar; Pieper, Florian; Hollensteiner, Karl J; Engler, Gerhard; Engel, Andreas K

2015-05-01

The integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. The earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (SC) and inferior colliculi (IC) are reciprocally connected in an audiovisual loop. Here, we investigate the mechanisms of audiovisual interaction in the midbrain by recording neural signals from the SC and IC simultaneously in anesthetized ferrets. Visual stimuli reliably produced band-limited phase locking of IC local field potentials (LFPs) in two distinct frequency bands: 6-10 and 15-30 Hz. These visual LFP responses co-localized with robust auditory responses that were characteristic of the IC. Imaginary coherence analysis confirmed that visual responses in the IC were not volume-conducted signals from the neighboring SC. Visual responses in the IC occurred later than retinally driven superficial SC layers and earlier than deep SC layers that receive indirect visual inputs, suggesting that retinal inputs do not drive visually evoked responses in the IC. In addition, SC and IC recording sites with overlapping visual spatial receptive fields displayed stronger functional connectivity than sites with separate receptive fields, indicating that visual spatial maps are aligned across both midbrain structures. Reciprocal coupling between the IC and SC therefore probably serves the dynamic integration of visual and auditory representations of space. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives.

PubMed

Ganou, C A; Eleftheriou, P Th; Theodosis-Nobelos, P; Fesatidou, M; Geronikaki, A A; Lialiaris, T; Rekka, E A

2018-02-01

PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC 50 = 4-45 μΜ, Ki = 2-23 μM), while only three thiazolyl derivatives showed low inhibition (best IC 50 = 18 μΜ, Ki = 9 μΜ). However, free binding energy (E) was in accordance with the IC 50 values only for some compounds. Docking analysis targeted to the whole enzyme revealed that the compounds exhibiting IC 50 values higher than expected could bind to other peripheral sites with lower free energy, E o , than when bound to the active/allosteric site. A prediction factor, E- (Σ Eo × 0.16), which takes into account lower energy binding to peripheral sites, was proposed and was found to correlate well with the IC 50 values following an asymmetrical sigmoidal equation with r 2 = 0.9692.

Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium

PubMed Central

Weil, Brian R.; Suzuki, Gen; Leiker, Merced M.; Fallavollita, James A.; Canty, John M.

2015-01-01

Rationale Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. Objective Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35×106) and CDCs (icCDCs, ~35×106) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). Methods and Results Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean ± SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 μm, icCDCs: 16.8±1.2 μm, vehicle: 20.2±3.7 μm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. Conclusions Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID:26271689

Migration to Current Open Source Technologies by MagIC Enables a More Responsive Website, Quicker Development Times, and Increased Community Engagement

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Koppers, A.; Constable, C.; Tauxe, L.; Jonestrask, L.

2017-12-01

The Magnetics Information Consortium (MagIC) supports an online database for the paleo, geo, and rock magnetic communities ( https://earthref.org/MagIC ). Researchers can upload data into the archive and download data as selected with a sophisticated search system. MagIC has completed the transition from an Oracle backed, Perl based, server oriented website to an ElasticSearch backed, Meteor based thick client website technology stack. Using JavaScript on both the sever and the client enables increased code reuse and allows easy offloading many computational operations to the client for faster response. On-the-fly data validation, column header suggestion, and spreadsheet online editing are some new features available with the new system. The 3.0 data model, method codes, and vocabulary lists can be browsed via the MagIC website and more easily updated. Source code for MagIC is publicly available on GitHub ( https://github.com/earthref/MagIC ). The MagIC file format is natively compatible with the PmagPy ( https://github.com/PmagPy/PmagPy) paleomagnetic analysis software. MagIC files can now be downloaded from the database and viewed and interpreted in the PmagPy GUI based tool, pmag_gui. Changes or interpretations of the data can then be saved by pmag_gui in the MagIC 3.0 data format and easily uploaded to the MagIC database. The rate of new contributions to the database has been increasing with many labs contributing measurement level data for the first time in the last year. Over a dozen file format conversion scripts are available for translating non-MagIC measurement data files into the MagIC format for easy uploading. We will continue to work with more labs until the whole community has a manageable workflow for contributing their measurement level data. MagIC will continue to provide a global repository for archiving and retrieving paleomagnetic and rock magnetic data and, with the new system in place, be able to more quickly respond to the community's requests for changes and improvements.

Structure-activity relationships of seco-prezizaane terpenoids in gamma-aminobutyric acid receptors of houseflies and rats.

PubMed

Kuriyama, Tadahiko; Schmidt, Thomas J; Okuyama, Emi; Ozoe, Yoshihisa

2002-06-01

Thirteen seco-prezizaane terpenoids isolated from star anise species (Illcium floridanum, Illcium parviflorum, and Illcium verum) were investigated for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB), a non-competitive antagonist of gamma-aminobutyric acid (GABA) receptors, to housefly-head and rat-brain membranes. Veranisatin A was found to be the most potent inhibitor in both membranes, with an IC(50)(fly) of 78.5 nM and an IC(50)(rat) of 271 nM, followed by anisatin (IC(50)(fly)=123 nM; IC(50)(rat)=282 nM). Six of the other 11 tested compounds were effective only in housefly-head membranes. Pseudoanisatin proved to display a high (>26-fold) selectivity for housefly versus rat GABA receptors (IC(50)(fly)=376 nM; IC(50)(rat) >10,000 nM). Although pseudoanisatin does not structurally resemble EBOB, Scatchard plots indicated that the two compounds bind to the same site in housefly receptors. Anisatin and pseudoanisatin exhibited moderate insecticidal activity against German cockroaches. Comparative molecular field analysis (CoMFA), a method of three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, demonstrated that seco-prezizaane terpenoids can bind to the same site as do picrotoxane terpenoids such as picrotoxinin and picrodendrins, and the CoMFA maps allowed us to identify the parts of the molecules essential to high activity in housefly GABA receptors.

Psychometric evaluation of an inpatient consumer survey measuring satisfaction with psychiatric care.

PubMed

Ortiz, Glorimar; Schacht, Lucille

2012-01-01

Measurement of consumers' satisfaction in psychiatric settings is important because it has been correlated with improved clinical outcomes and administrative measures of high-quality care. These consumer satisfaction measurements are actively used as performance measures required by the accreditation process and for quality improvement activities. Our objectives were (i) to re-evaluate, through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), the structure of an instrument intended to measure consumers' satisfaction with care in psychiatric settings and (ii) to examine and publish the psychometric characteristics, validity and reliability, of the Inpatient Consumer Survey (ICS). To psychometrically test the structure of the ICS, 34 878 survey results, submitted by 90 psychiatric hospitals in 2008, were extracted from the Behavioral Healthcare Performance Measurement System (BHPMS). Basic descriptive item-response and correlation analyses were performed for total surveys. Two datasets were randomly created for analysis. A random sample of 8229 survey results was used for EFA. Another random sample of 8261 consumer survey results was used for CFA. This same sample was used to perform validity and reliability analyses. The item-response analysis showed that the mean range for a disagree/agree five-point scale was 3.10-3.94. Correlation analysis showed a strong relationship between items. Six domains (dignity, rights, environment, empowerment, participation, and outcome) with internal reliabilities between good to moderate (0.87-0.73) were shown to be related to overall care satisfaction. Overall reliability for the instrument was excellent (0.94). Results from CFA provided support for the domains structure of the ICS proposed through EFA. The overall findings from this study provide evidence that the ICS is a reliable measure of consumer satisfaction in psychiatric inpatient settings. The analysis has shown the ICS to provide valid and reliable results and to focus on the specific concerns of consumers of psychiatric inpatient care. Scores by item indicate that opportunity for improvement exists across healthcare organizations.

Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation in First Complete Remission Can Abrogate the Poor Outcomes of Children with Acute Myeloid Leukemia Resistant to the First Course of Induction Chemotherapy.

PubMed

Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

2016-12-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy option for children with acute myeloid leukemia (AML) resistant to the first course of induction chemotherapy (IC 1st ). We aimed to identify the efficacy of unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first complete remission and whether children resistant (IC 1st -resistant; n = 38) or sensitive (IC 1st -sensitive; n = 59) to the IC 1st can achieve comparable outcomes. The cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) and severe chronic GVHD was .0% versus 20.1% (P = .038) and 21.7% versus 13.2% (P = .238), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was 22.2% versus 7.6% (P = .061) and 5.3% versus 10.8% (P = .364), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year probability of overall survival and disease-free survival was 76.3% versus 83.0% (P = .657) and 72.5% versus 81.6% (P = .396), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. Multivariate analysis failed to show significant differences in survival rates between the groups. Thus, our results show that unmanipulated haplo-HSCT may overcome the poor prognostic significance of IC 1st -resistance in children with AML, and it is valid as a postremission treatment for children with IC 1st -resistant AML lacking an HLA-matched donor. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Influence of the Prader-Willi syndrome imprinting center on the DNA methylation landscape in the mouse brain

PubMed Central

Brant, Jason O; Riva, Alberto; Resnick, James L; Yang, Thomas P

2014-01-01

Reduced representation bisulfite sequencing (RRBS) was used to analyze DNA methylation patterns across the mouse brain genome in mice carrying a deletion of the Prader-Willi syndrome imprinting center (PWS-IC) on either the maternally- or paternally-inherited chromosome. Within the ∼3.7 Mb imprinted Angelman/Prader-Willi syndrome (AS/PWS) domain, 254 CpG sites were interrogated for changes in methylation due to PWS-IC deletion. Paternally-inherited deletion of the PWS-IC increased methylation levels ∼2-fold at each CpG site (compared to wild-type controls) at differentially methylated regions (DMRs) associated with 5′ CpG island promoters of paternally-expressed genes; these methylation changes extended, to a variable degree, into the adjacent CpG island shores. Maternal PWS-IC deletion yielded little or no changes in methylation at these DMRs, and methylation of CpG sites outside of promoter DMRs also was unchanged upon maternal or paternal PWS-IC deletion. Using stringent ascertainment criteria, ∼750,000 additional CpG sites were also interrogated across the entire mouse genome. This analysis identified 26 loci outside of the imprinted AS/PWS domain showing altered DNA methylation levels of ≥25% upon PWS-IC deletion. Curiously, altered methylation at 9 of these loci was a consequence of maternal PWS-IC deletion (maternal PWS-IC deletion by itself is not known to be associated with a phenotype in either humans or mice), and 10 of these loci exhibited the same changes in methylation irrespective of the parental origin of the PWS-IC deletion. These results suggest that the PWS-IC may affect DNA methylation at these loci by directly interacting with them, or may affect methylation at these loci through indirect downstream effects due to PWS-IC deletion. They further suggest the PWS-IC may have a previously uncharacterized function outside of the imprinted AS/PWS domain. PMID:25482058

Influence of the Prader-Willi syndrome imprinting center on the DNA methylation landscape in the mouse brain.

PubMed

Brant, Jason O; Riva, Alberto; Resnick, James L; Yang, Thomas P

2014-11-01

Reduced representation bisulfite sequencing (RRBS) was used to analyze DNA methylation patterns across the mouse brain genome in mice carrying a deletion of the Prader-Willi syndrome imprinting center (PWS-IC) on either the maternally- or paternally-inherited chromosome. Within the ~3.7 Mb imprinted Angelman/Prader-Willi syndrome (AS/PWS) domain, 254 CpG sites were interrogated for changes in methylation due to PWS-IC deletion. Paternally-inherited deletion of the PWS-IC increased methylation levels ~2-fold at each CpG site (compared to wild-type controls) at differentially methylated regions (DMRs) associated with 5' CpG island promoters of paternally-expressed genes; these methylation changes extended, to a variable degree, into the adjacent CpG island shores. Maternal PWS-IC deletion yielded little or no changes in methylation at these DMRs, and methylation of CpG sites outside of promoter DMRs also was unchanged upon maternal or paternal PWS-IC deletion. Using stringent ascertainment criteria, ~750,000 additional CpG sites were also interrogated across the entire mouse genome. This analysis identified 26 loci outside of the imprinted AS/PWS domain showing altered DNA methylation levels of ≥25% upon PWS-IC deletion. Curiously, altered methylation at 9 of these loci was a consequence of maternal PWS-IC deletion (maternal PWS-IC deletion by itself is not known to be associated with a phenotype in either humans or mice), and 10 of these loci exhibited the same changes in methylation irrespective of the parental origin of the PWS-IC deletion. These results suggest that the PWS-IC may affect DNA methylation at these loci by directly interacting with them, or may affect methylation at these loci through indirect downstream effects due to PWS-IC deletion. They further suggest the PWS-IC may have a previously uncharacterized function outside of the imprinted AS/PWS domain.

Structural analysis of the intracellular domain of (pro)renin receptor fused to maltose-binding protein

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

Zhang, Yanfeng; Gao, Xiaoli; Michael Garavito, R., E-mail: garavito@msu.edu

2011-04-22

Highlights: {yields} Crystal structure of the intracellular domain of (pro)renin receptor (PRR-IC) as MBP fusion protein at 2.0 A (maltose-free) and 2.15 A (maltose-bound). {yields} MBP fusion protein is a dimer in crystals in the presence and absence of maltose. {yields} PRR-IC domain is responsible for the dimerization of the fusion protein. {yields} Residues in the PRR-IC domain, particularly two tyrosines, dominate the intermolecular interactions, suggesting a role for the PRR-IC domain in PRR dimerization. -- Abstract: The (pro)renin receptor (PRR) is an important component of the renin-angiotensin system (RAS), which regulates blood pressure and cardiovascular function. The integral membranemore » protein PRR contains a large extracellular domain ({approx}310 amino acids), a single transmembrane domain ({approx}20 amino acids) and an intracellular domain ({approx}19 amino acids). Although short, the intracellular (IC) domain of the PRR has functionally important roles in a number of signal transduction pathways activated by (pro)renin binding. Meanwhile, together with the transmembrane domain and a small portion of the extracellular domain ({approx}30 amino acids), the IC domain is also involved in assembly of V{sub 0} portion of the vacuolar proton-translocating ATPase (V-ATPase). To better understand structural and multifunctional roles of the PRR-IC, we report the crystal structure of the PRR-IC domain as maltose-binding protein (MBP) fusion proteins at 2.0 A (maltose-free) and 2.15 A (maltose-bound). In the two separate crystal forms having significantly different unit-cell dimensions and molecular packing, MBP-PRR-IC fusion protein was found to be a dimer, which is different with the natural monomer of native MBP. The PRR-IC domain appears as a relatively flexible loop and is responsible for the dimerization of MBP fusion protein. Residues in the PRR-IC domain, particularly two tyrosines, dominate the intermonomer interactions, suggesting a role for the PRR-IC domain in protein oligomerization.« less

Intellectual capital in the healthcare sector: a systematic review and critique of the literature.

PubMed

Evans, Jenna M; Brown, Adalsteinn; Baker, G Ross

2015-12-15

Variations in the performance of healthcare organizations may be partly explained by differing "stocks" of intellectual capital (IC), and differing approaches and capacities for leveraging IC. This study synthesizes what is currently known about the conceptualization, management and measurement of IC in healthcare through a review of the literature. Peer-reviewed papers on IC in healthcare published between 1990 and 2014 were identified through searches of five databases using the following key terms: intellectual capital/assets, knowledge capital/assets/resources, and intangible assets/resources. Articles deemed relevant for inclusion underwent systematic data extraction to identify overarching themes and were assessed for their methodological quality. Thirty-seven papers were included in the review. The primary research method used was cross-sectional questionnaires focused on hospital managers' perceptions of IC, followed by semi-structured interviews and analysis of administrative data. Empirical studies suggest that IC is linked to subjective process and performance indicators in healthcare organizations. Although the literature on IC in healthcare is growing, it is not advanced. In this paper, we identify and examine the conceptual, theoretical and methodological limitations of the literature. The concept and framework of IC offer a means to study the value of intangible resources in healthcare organizations, how to manage systematically these resources together, and their mutually enhancing interactions on performance. We offer several recommendations for future research.

Ionospheric Caustics in Solar Radio Observations

NASA Astrophysics Data System (ADS)

Koval, A.; Chen, Y.; Stanislavsky, A.

2016-12-01

The Earth ionosphere possesses by natural focusing and defocusing effects on radio waves due to presence of variable ionospheric irregularities which could act like convergent and divergent lenses on incident radiation. In particular, the focusing of emission from the Sun was firstly detected on the Nançay Decameter Array dynamic spectra in the 1980s. On time-frequency spectrograms the intensity variations form specific structures different from well-known solar radio bursts and clearly distinguishing on a background of solar radiation. Such structures have been identified as ionospheric caustics (ICs) and considered to be the result of radio waves refraction on medium scale travelling ionospheric disturbances (MSTIDs). Although nowadays the ICs are registered by different radio observatories due to augmentation of low-frequency radio telescopes, the most recent papers devoted to ICs in solar radio records date back to the 1980s. In this study, we revisit the ICs issue with some new results by conducting a statistical analysis of occurrence rate of ICs in solar dynamic spectra in meter-decameter wavelength range for long continuous period (15 years). The seasonal variations in ICs appearance have been found for the first time. Besides, we report the possible solar cycle dependence of ICs emergence. The radio waves propagation in the ionosphere comprising MSTIDs will be considered. The present research renews the subject of ICs in the low-frequency solar radio astronomy after about 35-year letup.

Surveying the Commons: Current Implementation of Information Commons Web sites

ERIC Educational Resources Information Center

Leeder, Christopher

2009-01-01

This study assessed the content of 72 academic library Information Commons (IC) Web sites using content analysis, quantitative assessment and qualitative surveys of site administrators to analyze current implementation by the academic library community. Results show that IC Web sites vary widely in content, design and functionality, with few…

Individualism-Collectivism: Links to Occupational Plans and Work Values

ERIC Educational Resources Information Center

Hartung, Paul J.; Fouad, Nadya A.; Leong, Frederick T. L.; Hardin, Erin E.

2010-01-01

Individualism-collectivism (IC) constitutes a cultural variable thought to influence a wide variety of variables including career planning and decision making. To examine this possibility, college students (216 women, 106 men, 64% racial-ethnic minorities) responded to measures of IC, occupational plans, and work values. Multivariate analysis of…

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

Skillman, Evan D.; Hidalgo, Sebastian L.; Monelli, Matteo

We present an analysis of the star formation history (SFH) of a field near the half-light radius in the Local Group dwarf irregular galaxy IC 1613 based on deep Hubble Space Telescope Advanced Camera for Surveys imaging. Our observations reach the oldest main sequence turn-off, allowing a time resolution at the oldest ages of ∼1 Gyr. Our analysis shows that the SFH of the observed field in IC 1613 is consistent with being constant over the entire lifetime of the galaxy. These observations rule out an early dominant episode of star formation in IC 1613. We compare the SFH ofmore » IC 1613 with expectations from cosmological models. Since most of the mass is in place at early times for low-mass halos, a naive expectation is that most of the star formation should have taken place at early times. Models in which star formation follows mass accretion result in too many stars formed early and gas mass fractions that are too low today (the 'over-cooling problem'). The depth of the present photometry of IC 1613 shows that, at a resolution of ∼1 Gyr, the star formation rate is consistent with being constant, at even the earliest times, which is difficult to achieve in models where star formation follows mass assembly.« less

Effects of inorganic carbon on the nitrous oxide emissions and microbial diversity of an anaerobic ammonia oxidation reactor.

PubMed

Zhang, Wenjie; Wang, Dunqiu; Jin, Yue

2018-02-01

Inorganic carbon (IC) is important for anaerobic ammonium oxidation (anammox). In this study, the effects of the IC concentration on N 2 O emissions and microbial diversity in an anammox reactor were investigated. N 2 O emissions were positively correlated with IC concentrations, and IC concentrations in the range of 55-130 mg/L were optimal, considering the nitrogen removal rate and N 2 O emissions. High IC concentrations resulted in the formation of CaCO 3 on the surface of anammox granules, which impacted the diffusion conditions of the substrate. Microbial community analysis indicated that high IC concentrations decreased the populations of specific bacteria, such as Achromobacter spanius strain YJART-7, Achromobacter xylosoxidans strain IHB B 6801, and Denitratisoma oestradiolicum clone 20b_15. D. oestradiolicum clone 20b_15 appeared to be the key contributor to N 2 O emissions. High N 2 O emissions may result from changes in organic carbon sources, which lead to denitrification by D. oestradiolicum clone 20b_15. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ion chromatography-mass spectrometry: a review of recent technologies and applications in forensic and environmental explosives analysis.

PubMed

Barron, Leon; Gilchrist, Elizabeth

2014-01-02

The development and application of ion chromatography (IC) coupled to mass spectrometry (MS) is discussed herein for the quantitative determination of low-order explosives-related ionic species in environmental and forensic sample types. Issues relating to environmental explosives contamination and the need for more confirmatory IC-MS based applications in forensic science are examined. In particular, the compatibility of a range of IC separation modes with MS detection is summarised along with the analytical challenges that have been overcome to facilitate determinations at the ng-μg L(-1) level. Observed trends in coupling IC to inductively coupled plasma and electrospray ionisation mass spectrometry form a particular focus. This review also includes a discussion of the relative performance of reported IC-MS methods in comparison to orthogonal ion separation-based, spectrometric and spectroscopic approaches to confirmatory detection of low-order explosives. Finally, some promising areas for future research are highlighted and discussed with respect to potential IC-MS applications. Copyright © 2013 Elsevier B.V. All rights reserved.

On-Die Sensors for Transient Events

NASA Astrophysics Data System (ADS)

Suchak, Mihir Vimal

Failures caused by transient electromagnetic events like Electrostatic Discharge (ESD) are a major concern for embedded systems. The component often failing is an integrated circuit (IC). Determining which IC is affected in a multi-device system is a challenging task. Debugging errors often requires sophisticated lab setups which require intentionally disturbing and probing various parts of the system which might not be easily accessible. Opening the system and adding probes may change its response to the transient event, which further compounds the problem. On-die transient event sensors were developed that require relatively little area on die, making them inexpensive, they consume negligible static current, and do not interfere with normal operation of the IC. These circuits can be used to determine the pin involved and the level of the event in the event of a transient event affecting the IC, thus allowing the user to debug system-level transient events without modifying the system. The circuit and detection scheme design has been completed and verified in simulations with Cadence Virtuoso environment. Simulations accounted for the impact of the ESD protection circuits, parasitics from the I/O pin, package and I/O ring, and included a model of an ESD gun to test the circuit's response to an ESD pulse as specified in IEC 61000-4-2. Multiple detection schemes are proposed. The final detection scheme consists of an event detector and a level sensor. The event detector latches on the presence of an event at a pad, to determine on which pin an event occurred. The level sensor generates current proportional to the level of the event. This current is converted to a voltage and digitized at the A/D converter to be read by the microprocessor. Detection scheme shows good performance in simulations when checked against process variations and different kind of events.

Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model.

PubMed

Cashman, J D; Clark-Lewis, I; Eaves, A C; Eaves, C J

1999-12-01

Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice transplanted with human cord blood or adult marrow cells and injected 6 weeks posttransplant with 2 daily doses of transforming growth factor-beta(1) (TGF-beta(1)), monocyte chemoattractant protein-1 (MCP-1), or a nonaggregating form of macrophage inflammatory protein-1alpha (MIP-1alpha) showed unique patterns of inhibition of human progenitor proliferation 1 day later. TGF-beta(1) was active on long-term culture initiating cells (LTC-IC) and on primitive erythroid and granulopoietic colony-forming cells (HPP-CFC), but had no effect on mature CFC. MCP-1 inhibited the cycling of both types of HPP-CFC but not LTC-IC. MIP-1alpha did not inhibit either LTC-IC or granulopoietic HPP-CFC but was active on erythroid HPP-CFC and mature granulopoietic CFC. All of these responses were independent of the source of human cells transplanted. LTC-IC of either human cord blood or adult marrow origin continue to proliferate in NOD/SCID mice for many weeks, although the turnover of all types of human CFC in mice transplanted with adult human marrow (but not cord blood) is downregulated after 6 weeks. Interestingly, administration of either MIP-1beta, an antagonist of both MIP-1alpha and MCP-1 or MCP-1(9-76), an antagonist of MCP-1 (and MCP-2 and MCP-3), into mice in which human marrow-derived CFC had become quiescent, caused the rapid reactivation of these progenitors in vivo. These results provide the first definition of stage-specific inhibitors of human hematopoietic progenitor cell cycling in vivo. In addition they show that endogenous chemokines can contribute to late graft failure, which can be reversed by the administration of specific antagonists.

Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

PubMed Central

Venegas, Carmen; Arenas, Alex; Rada, Gabriel

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has shown benefit in inhibit collagen production and has also demonstrated benefit in decline progression in IPF in physiological outcomes as Forced vital capacity (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit in mortality but no in clinically relevant outcomes as exacerbations or worsening of IPF. Methods: We conducted a systematic review to evaluate the effectiveness of physiological and clinical outcomes of pirfenidone compared to placebo in IPF. We performed a search with no language restriction. Two researchers performed literature search, quality assessment, data extraction and analysis. And was performed a summary of findings table following the GRADE approach. Results: We included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32–0.88) and IPF related mortality (RR 0.32 IC 0.14–0.75); other outcomes evaluated were worsening of IPF (RR 0.64 IC 0.50–0.83) and acute exacerbation (RR: 0.72 IC 0.30–1.66 respectively). Also there was a decrease in progression free survival (PFS) (RR 0.83 IC 0.74–0.92) compared to placebo. Conclusions: We observed significant differences in physiologic and clinically relevant outcomes such as reduction in all-cause mortality, IPF related mortality, worsening and exacerbation of IPF and PFS. So pirfenidone treatment should be considered not only for its benefits in pulmonary function tests but also by its clinically relevant outcomes. PMID:26308723

A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

PubMed

Rades, Dirk; Janssen, Stefan; Dziggel, Liesa; Blanck, Oliver; Bajrovic, Amira; Veninga, Theo; Schild, Steven E

2017-01-06

This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

Studies of new media radiation induced laser

NASA Technical Reports Server (NTRS)

Han, K. S.; Shiu, Y. J.; Raju, S. R.; Hwang, I. H.; Tabibi, B.

1984-01-01

Various lasants were investigated especially, 2-iodohepafluoropropane (i-C3F7I) for the direct solar pumped lasers. Optical pumping of iodine laser was achieved using a small flashlamp. Using i-C3F7I as a laser gain medium, threshold inversion density, small signal gain, and laser performance at the elevated temperature were measured. The experimental results and analysis are presented. The iodine laser kinetics of the C3F7I and IBr system were numerically simulated. The concept of a direct solar-pumped laser amplifier using (i-C3F7I) as the laser material was evaluated and several kinetic coefficients for i-C3F7I laser system were reexamined. The results are discussed.

Assessing the Blood Supply Status of the Focal Ground-Glass Opacity in Lungs Using Spectral Computed Tomography.

PubMed

Liu, Guanfu; Li, Mengying; Li, Guosheng; Li, Zhiyong; Liu, Ailian; Pu, Renwang; Cao, Huizhi; Liu, Yijun

2018-01-01

To exploit material decomposition analysis in dual-energy spectral computed tomography (CT) to assess the blood supply status of the ground-glass opacity (GGO) in lungs. This retrospective study included 48 patients with lung adenocarcinoma, who underwent a contrast-enhanced dual-energy spectral CT scan before treatment (53 GGOs in total). The iodine concentration (IC) and water content (WC) of the GGO, the contralateral and ipsilateral normal lung tissues were measured in the arterial phase (AP) and their differences were analyzed. IC, normalized IC (NIC), and WC values were compared between the pure ground-glass opacity (pGGO) and the mixed ground-glass opacity (mGGO), and between the group of preinvasive lesions and the minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) groups. The values of pGGO (IC = 20.9 ± 6.2 mg/mL and WC = 345.1 ± 87.1 mg/mL) and mGGO (IC = 23.8 ± 8.3 mg/mL and WC = 606.8 ± 124.5 mg/mL) in the AP were significantly higher than those of the contralateral normal lung tissues (IC = 15.0 ± 4.9 mg/mL and WC = 156.4 ± 36.8 mg/mL; IC = 16.2 ± 5.7 mg/mL and WC = 169.4 ± 41.0 mg/mL) and ipsilateral normal lung tissues (IC = 15.1 ± 6.2 mg/mL and WC = 156.3 ± 38.8 mg/mL; IC = 15.9 ± 6.0 mg/mL and WC = 174.7 ± 39.2 mg/mL; all p < 0.001). After normalizing the data according to the values of the artery, pGGO (NIC = 0.1 and WC = 345.1 ± 87.1 mg/mL) and mGGO (NIC = 0.2 and WC = 606.8 ± 124.5 mg/mL) were statistically different ( p = 0.049 and p < 0.001, respectively), but not for the IC value ( p = 0.161). The WC values of the group with preinvasive lesions and MIA (345.4 ± 96.1 mg/mL) and IA (550.1 ± 158.2 mg/mL) were statistically different ( p < 0.001). Using dual-energy spectral CT and material decomposition analysis, the IC in GGO can be quantitatively measured which can be an indicator of the blood supply status in the GGO.

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

PubMed Central

Postma, Dirkje S.; Dekhuijzen, Richard; van der Molen, Thys; Martin, Richard J.; van Aalderen, Wim; Roche, Nicolas; Guilbert, Theresa W.; Israel, Elliot; van Eickels, Daniela; Khalid, Javaria Mona; Herings, Ron M.C.; Overbeek, Jetty A.; Miglio, Cristiana; Thomas, Victoria; Hutton, Catherine; Hillyer, Elizabeth V.

2017-01-01

Purpose Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). Methods This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. Results Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. Conclusions In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS. PMID:28102056

Infection control and prevention practices implemented to reduce transmission risk of Middle East respiratory syndrome-coronavirus in a tertiary care institution in Saudi Arabia.

PubMed

Butt, Taimur S; Koutlakis-Barron, Irene; AlJumaah, Suliman; AlThawadi, Sahar; AlMofada, Saleh

2016-05-01

Transmission of Middle East respiratory syndrome-coronavirus (MERS-CoV) among health care workers (HCWs) and patients has been documented with mortality rate approximating 36%. We propose advanced infection control measures (A-IC) used in conjunction with basic infection control measures (B-IC) help reduce pathogen transmission. B-IC include standard and transmission-based precautions. A-IC are initiatives implemented within our center to enhance effectiveness of B-IC. Study effectiveness of combining B-IC and A-IC to prevent transmission of MERS-CoV to HCWs. A retrospective observational study was undertaken. A-IC measures include administrative support with daily rounds; infection control risk assessment; timely screening, isolation, and specimen analysis; collaboration; epidemic planning; stockpiling; implementation of contingency plans; full personal protective equipment use for advanced airway management; use of a real-time electronic isolation flagging system; infection prevention and control team on-call protocols; pretransfer MERS-CoV testing; and education. A total of 874 real-time polymerase chain reaction MERS-CoV tests were performed during the period beginning July 1, 2013, and ending January 31, 2015. Six hundred ninety-four non-HCWs were tested, of these 16 tested positive for MERS-CoV and their infection was community acquired. Sixty-nine percent of the confirmed MERS-CoV-positive cases were men, with an average age of 56 years (range, 19-84 years). Of the total tested for MERS-CoV, 180 individuals were HCWs with zero positivity. Adhering to a combination of B-IC and A-IC reduces the risk of MERS-CoV transmission to HCWs. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Health care service utilization among patients with bladder pain syndrome/interstitial cystitis in a single payer healthcare system.

PubMed

Chung, Shiu-Dong; Liu, Shih-Ping; Li, Hsien-Chang; Lin, Herng-Ching

2014-01-01

This study aims to investigate the differences in the utilization of healthcare services between patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and patients without using a population-based database in Taiwan. This study comprised of 350 patients with BPS/IC and 1,750 age-matched controls. Healthcare resource utilization was evaluated in the one-year follow-up period as follows: number of outpatient visits and inpatient days, and the mean costs of outpatient and inpatient treatment. A multivariate regression analysis was used to evaluate the relationship between BPS/IC and total costs of health care services. For urological services, patients with BPS/IC had a significantly higher number of outpatient visits (2.5 vs. 0.2, p<0.001) as well as significantly higher outpatient costs ($US166 vs. $US6.8, p<0.001) than the controls. For non-urologic services, patients with BPS/IC had a significantly high number of outpatient visits (35.0 vs. 21.3, p<0.001) as well as significantly higher outpatient cots ($US912 vs. $US675, p<0.001) as compared to the controls. Overall, patients with BPS/IC had 174% more outpatient visits and 150% higher total costs than the controls. Multiple-regression-analyses also showed that the patients with BPS/IC had significantly higher total costs for all healthcare services than the controls. This study found that patients with BPS/IC have a significantly higher number of healthcare related visits, and have significantly higher healthcare related costs than age-matched controls. The high level of healthcare services utilization accrued with BPS/IC was not necessarily exclusive for BPS/IC, but may have also been associated with medical co-morbidities.

Interpersonal Callousness from Childhood to Adolescence: Developmental Trajectories and Early Risk Factors.

PubMed

Byrd, Amy L; Hawes, Samuel W; Loeber, Rolf; Pardini, Dustin A

2018-01-01

Youth with a callous interpersonal style, consistent with features of adult psychopathy (e.g., lack of guilt, deceitful), are at risk for exhibiting severe and protracted antisocial behaviors. However, no studies have examined changes that occur in interpersonal callousness (IC) from childhood to adolescence, and little is known about the influence of early child, social, and contextual factors on trajectories of IC. The current study examined distinct patterns of IC across childhood and adolescence and associations with early risk factors. Participants were an at-risk sample of 503 boys (56% African American) assessed annually from around ages 7-15. Analyses examined child (anger dysregulation, fearfulness), social (peer, family, maltreatment), and contextual (psychosocial adversity) factors associated with teacher-reported IC trajectories across childhood and adolescence. Using latent class growth analysis, five trajectories of IC were identified (early-onset chronic, childhood-limited, adolescent-onset, moderate, low). Approximately 10% of boys followed an early-onset chronic trajectory, and a roughly equal percent of youth followed childhood-limited trajectory (10%) or an adolescent-onset trajectory (12%) of IC across development. Specifically, half of the boys with high IC in childhood did not continue to exhibit significant levels of these features into adolescence, whereas an equal proportion of youth with low IC in childhood demonstrated increasing levels during the transition to adolescence. Boys in the early-onset chronic group were characterized by the most risk factors and were differentiated from those with childhood-limited and adolescent-onset IC only by higher conduct problems, fearlessness, and emotional abuse/neglect. Findings are discussed in terms of developmental models of IC and several avenues for early targeted interventions.

In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus.

PubMed

Arbab, Ahmed Hassan; Parvez, Mohammad Khalid; Al-Dosari, Mohammed Salem; Al-Rehaily, Adnan Jathlan

2017-07-01

Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC 50 ) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC 50 =10.65), Pulicaria crispa (ethyl acetate extract, IC 50 =14.45), Coccinea grandis (total ethanol extract, IC 50 =31.57), Fumaria parviflora (hexane extract, IC 50 =35.44), Capparis decidua (aqueous extract, IC 50 =66.82), Corallocarpus epigeus (total ethanol extract, IC 50 =71.9), Indigofera caerulea (methanol extract, IC 50 =73.21), Abutilon figarianum (dichloromethane extract, IC 50 =99.76) and Acacia oerfota (total ethanol extract, IC 50 =101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua , C. epigeus, A. figarianum , A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.

VizieR Online Data Catalog: IN-SYNC. III. Radial velocities of IC348 stars (Cottaar+, 2015)

NASA Astrophysics Data System (ADS)

Cottaar, M.; Covey, K. R.; Foster, J. B.; Meyer, M. R.; Tan, J. C.; Nidever, D. L.; Drew Chojnowski, S.; da Rio, N.; Flaherty, K. M.; Frinchaboy, P. M.; Majewski, S.; Skrutskie, M. F.; Wilson, J. C.; Zasowski, G.

2015-11-01

Cottaar et al. (Paper I, 2014, J/ApJ/794/125) describes the analysis of the high-resolution near-infrared spectra obtained by the APOGEE multi-object spectrograph from stars in IC 348, NGC 1333, NGC 2264, and Orion A as part of the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) ancillary program. Using radial velocities determined from APOGEE spectra of 380 likely cluster members, we have measured the radial velocity distribution of the young (2-6Myr) cluster IC 348. (2 data files).

Effect of in ovo feeding of dextrin-iodinated casein in broilers: II. Hatch window and growth performance.

PubMed

Abousaad, S; Lassiter, K; Piekarski, A; Chary, P; Striplin, K; Christensen, K; Bielke, L R; Hargis, B M; Dridi, S; Bottje, W G

2017-05-01

Studies were conducted using a commercial InovojectTM system to determine effects of in ovo feeding of dextrin and iodinated casein (IC) on hatch and posthatch growth in broilers. At ∼18.5 d embryonic development, eggs were treated with 0, 240, or 480 μg IC/mL in saline (Cont, IC240, and IC480) or dextrin (Dext, DextIC240 and DextIC480). The Dext solution consisted of 18% maltodextrin and 10% potato starch dextrin; saline was the vehicle used by the company for in ovo vaccination. The volume for all in ovo treatments was 50 μL/injection. Eggs in Experiment 1 were transferred to a commercial hatcher unit whereas eggs in Experiments 2 and 3 were transferred to a research hatcher unit to assess effects of treatments on timing of hatch. At hatch, chicks were randomly selected and placed in floor pens and grown to 6 wk. In Experiment 1, there were no differences in hatch weights, but broilers provided Dext IC240 in ovo were heavier (P < 0.05) at 6 wk compared to other treatments with the exception of the Dext IC240 group. In Experiment 2, hatch weights were heavier (P < 0.05) in chicks receiving IC240 and DexIC480 treatments compared to Controls. At 6 wk, broilers in all treatments were heavier (P < 0.05) than Cont with the exception of IC480. In Experiment 3, hatch was stimulated by IC240 (in saline), but was delayed by Dext IC240. Serum analysis of β-hydroxybutyrate (μM/mL), as an indicator of ketone accumulation from fat metabolism of chicks held in chick boxes for 24 h posthatch (to simulate delay in placement after hatch), indicated that chicks in the IC240 group (that hatched earlier) had higher blood ketones compared to chicks that received Dext or DextIC240 in ovo (that hatched later). We conclude dextrin and iodinated casein (240 μg/mL) provided in ovo (∼18.5 d of embryonic development) has the potential to improve chick quality and posthatch body weight by delaying or narrowing hatch window. © 2016 Poultry Science Association Inc.

Aspirin resistance in patients with hemodynamic cerebral ischemia undergoing extracranial-intracranial bypass surgery.

PubMed

Jussen, Daniel; Horn, Peter; Vajkoczy, Peter

2013-01-01

Aspirin (acetylsalicylic acid, ASA) is the treatment of choice for prevention of vascular events in symptomatic steno-occlusive cerebrovascular disease (CVD). Cerebral revascularization using standard extracranial-intracranial (EC-IC) bypass surgery may be used to revert hemodynamic compromise. Aspirin is prescribed as standard medication in order to avoid bypass failure. Accumulating evidence of an increased risk of major adverse clinical events led to this study, in which we aimed to assess the prevalence of aspirin resistance and prothrombotic disorders among patients scheduled for EC-IC bypass surgery, and the effectiveness of aspirin dose escalation. We prospectively screened patients with circumscribed high-grade stenosis or occlusion of brain-supplying vessels fulfilling the hemodynamic criteria for EC-IC bypass surgery for aspirin resistance using a platelet function analyzer (PFA-100®) test. We also determined their smoking habits and screened for prothrombotic disorders and comorbidities. The patients were divided into 2 major groups: group A had atherosclerotic steno-occlusive CVD and group B consisted of patients with nonatherosclerotic steno-occlusive CVD (moyamoya disease) and a subgroup of pediatric moyamoya patients (pediatric subgroup). Bypass patency was documented via digital subtraction angiography. Standard initial ASA dose applied was 100 mg/day. In cases of aspirin resistance, doses were increased and the PFA-100 test was repeated. A total of 56 patients were included over a time period of 6 months. In group A (n = 25), we found a ratio of 40% of patients with primary resistance to aspirin 100 mg/day. In contrast, in group B (n = 25), only 20% of the patients were resistant to aspirin 100 mg/day; in the pediatric population (n = 6), there was no primary aspirin resistance. After a dose escalation to 300 mg/day, the ratio of aspirin resistance was reduced to 20% in group A and to 0% in group B. Altogether 5 patients with atherosclerotic steno-occlusive CVD remained aspirin-resistant despite the dose escalation; 2 of them suffered an early bypass failure. Smoking habits and diabetes mellitus were positively correlated with aspirin resistance. Moreover, 25% of all patients had laboratory signs of a prothrombotic disorder, but this had no influence on aspirin response or bypass patency. Aspirin resistance is common in the population of patients with hemodynamic cerebral ischemia scheduled for cerebral revascularization. It may have an adverse impact on the outcome of surgery. Screening and treatment via dose escalation of aspirin is a straightforward and sensible routine for patients undergoing EC-IC bypass surgery. Copyright © 2013 S. Karger AG, Basel.

Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

PubMed Central

DiSantostefano, Rachael L.; Sampson, Tim; Le, Hoa Van; Hinds, David; Davis, Kourtney J.; Bakerly, Nawar Diar

2014-01-01

Introduction Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. Objective To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. Methods Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002–2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. Outcomes: severe pneumonia (primary) and any pneumonia (secondary). Results Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. Conclusions The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20–50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD. PMID:24878543

Regulatory Elements Associated with Paternally-Expressed Genes in the Imprinted Murine Angelman/Prader-Willi Syndrome Domain

PubMed Central

Khadake, Jyoti; Heggestad, Arnold D.; Ma, Xiaojie; Johnstone, Karen A.; Resnick, James L.; Yang, Thomas P.

2013-01-01

The Angelman/Prader-Willi syndrome (AS/PWS) domain contains at least 8 imprinted genes regulated by a bipartite imprinting center (IC) associated with the SNRPN gene. One component of the IC, the PWS-IC, governs the paternal epigenotype and expression of paternal genes. The mechanisms by which imprinting and expression of paternal genes within the AS/PWS domain – such as MKRN3 and NDN – are regulated by the PWS-IC are unclear. The syntenic region in the mouse is organized and imprinted similarly to the human domain with the murine PWS-IC defined by a 6 kb interval within the Snrpn locus that includes the promoter. To identify regulatory elements that may mediate PWS-IC function, we mapped the location and allele-specificity of DNase I hypersensitive (DH) sites within the PWS-IC in brain cells, then identified transcription factor binding sites within a subset of these DH sites. Six major paternal-specific DH sites were detected in the Snrpn gene, five of which map within the 6 kb PWS-IC. We postulate these five DH sites represent functional components of the murine PWS-IC. Analysis of transcription factor binding within multiple DH sites detected nuclear respiratory factors (NRF's) and YY1 specifically on the paternal allele. NRF's and YY1 were also detected in the paternal promoter region of the murine Mrkn3 and Ndn genes. These results suggest that NRF's and YY1 may facilitate PWS-IC function and coordinately regulate expression of paternal genes. The presence of NRF's also suggests a link between transcriptional regulation within the AS/PWS domain and regulation of respiration. 3C analyses indicated Mkrn3 lies in close proximity to the PWS-IC on the paternal chromosome, evidence that the PWS-IC functions by allele-specific interaction with its distal target genes. This could occur by allele-specific co-localization of the PWS-IC and its target genes to transcription factories containing NRF's and YY1. PMID:23390487

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

Prentice, S. J.; Mazzali, P. A.; Pian, E.

The optical and optical/near-infrared pseudo-bolometric light curves of 85 stripped-envelope supernovae (SNe) are constructed using a consistent method and a standard cosmology. The light curves are analysed to derive temporal characteristics and peak luminosity L p , enabling the construction of a luminosity function. Subsequently, the mass of 56 Ni synthesized in the explosion, along with the ratio of ejecta mass to ejecta kinetic energy, are found. Analysis shows that host-galaxy extinction is an important factor in accurately determining luminosity values as it is significantly greater than Galactic extinction in most cases. It is found that broad-lined SNe Ic (SNemore » Ic-BL) and gamma-ray burst SNe are the most luminous subtypes with a combined median L p , in erg s -1 , of log(L p) = 43.00 compared to 42.51 for SNe Ic, 42.50 for SNe Ib, and 42.36 for SNe IIb. It is also found that SNe Ic-BL synthesize approximately twice the amount of 56Ni compared with SNe Ic, Ib, and IIb, with median M Ni = 0.34, 0.16, 0.14, and 0.11 M ⊙ , respectively. SNe Ic-BL, and to a lesser extent SNe Ic, typically rise from L p /2 to L p more quickly than SNe Ib/IIb; consequently, their light curves are not as broad.« less

Iterative categorization (IC): a systematic technique for analysing qualitative data

PubMed Central

2016-01-01

Abstract The processes of analysing qualitative data, particularly the stage between coding and publication, are often vague and/or poorly explained within addiction science and research more broadly. A simple but rigorous and transparent technique for analysing qualitative textual data, developed within the field of addiction, is described. The technique, iterative categorization (IC), is suitable for use with inductive and deductive codes and can support a range of common analytical approaches, e.g. thematic analysis, Framework, constant comparison, analytical induction, content analysis, conversational analysis, discourse analysis, interpretative phenomenological analysis and narrative analysis. Once the data have been coded, the only software required is a standard word processing package. Worked examples are provided. PMID:26806155

Impact of Integrated Care Model (ICM) on Direct Medical Costs in Management of Advanced Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Bandurska, Ewa; Damps-Konstańska, Iwona; Popowski, Piotr; Jędrzejczyk, Tadeusz; Janowiak, Piotr; Świętnicka, Katarzyna; Zarzeczna-Baran, Marzena; Jassem, Ewa

2017-06-12

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a commonly diagnosed condition in people older than 50 years of age. In advanced stage of this disease, integrated care (IC) is recommended as an optimal approach. IC allows for holistic and patient-focused care carried out at the patient's home. The aim of this study was to analyze the impact of IC on costs of care and on demand for medical services among patients included in IC. MATERIAL AND METHODS The study included 154 patients diagnosed with advanced COPD. Costs of care (general, COPD, and exacerbations-related) were evaluated for 1 year, including 6-months before and after implementing IC. The analysis included assessment of the number of medical procedures of various types before and after entering IC and changes in medical services providers. RESULTS Direct medical costs of standard care in advanced COPD were 886.78 EUR per 6 months. Costs of care of all types decreased after introducing IC. Changes in COPD and exacerbation-related costs were statistically significant (p=0.012492 and p=0.017023, respectively). Patients less frequently used medical services for respiratory system and cardiovascular diseases. Similarly, the number of hospitalizations and visits to emergency medicine departments decreased (by 40.24% and 8.5%, respectively). The number of GP visits increased after introducing IC (by 7.14%). CONCLUSIONS The high costs of care in advanced COPD indicate the need for new forms of effective care. IC caused a decrease in costs and in the number of hospitalization, with a simultaneous increase in the number of GP visits.

Integrating marker-assisted background analysis with foreground selection for pyramiding bacterial blight resistance genes into Basmati rice.

PubMed

Baliyan, Nikita; Malik, Rekha; Rani, Reema; Mehta, Kirti; Vashisth, Urvashi; Dhillon, Santosh; Boora, Khazan Singh

2018-01-01

Bacterial leaf blight (BB), caused by the bacterium Xanthomonas oryzae pv. Oryzae (Xoo), is the major constraint amongst rice diseases in India. CSR-30 is a very popular high-yielding, salt-tolerant Basmati variety widely grown in Haryana, India, but highly susceptible to BB. In the present study, we have successfully introgressed three BB resistance genes (Xa21, xa13 and xa5) from BB-resistant donor variety IRBB-60 into the BB-susceptible Basmati variety CSR-30 through marker-assisted selection (MAS) exercised with stringent phenotypic selection without compromising the Basmati traits. Background analysis using 131 polymorphic SSR markers revealed that recurrent parent genome (RPG) recovery ranged up to 97.1% among 15 BC 3 F 1 three-gene-pyramided genotypes. Based on agronomic evaluation, BB reaction, aroma, percentage recovery of RPG, and grain quality evaluation, four genotypes, viz., IC-R28, IC-R68, IC-R32, and IC-R42, were found promising and advanced to BC 3 F 2 generation. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Neural Processing of Target Distance by Echolocating Bats: Functional Roles of the Auditory Midbrain

PubMed Central

Wenstrup, Jeffrey J.; Portfors, Christine V.

2011-01-01

Using their biological sonar, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. The mustached bat's auditory midbrain (inferior colliculus, IC) is crucial to the analysis of pulse-echo delay. IC neurons are selective for certain delays between frequency modulated (FM) elements of the pulse and echo. One role of the IC is to create these “delay-tuned”, “FM-FM” response properties through a series of spectro-temporal integrative interactions. A second major role of the midbrain is to project target distance information to many parts of the brain. Pathways through auditory thalamus undergo radical reorganization to create highly ordered maps of pulse-echo delay in auditory cortex, likely contributing to perceptual features of target distance analysis. FM-FM neurons in IC also project strongly to pre-motor centers including the pretectum and the pontine nuclei. These pathways may contribute to rapid adjustments in flight, body position, and sonar vocalizations that occur as a bat closes in on a target. PMID:21238485

The indirect costs of psoriatic arthritis: systematic review and meta-analysis.

PubMed

Kawalec, Paweł; Malinowski, Krzysztof Piotr

2015-02-01

The aim of this systematic review is to collect all current data on the indirect costs (IC) related to psoriatic arthritis (PsA). The search was conducted using MEDLINE (via PubMed), Embase and Centre for Reviews and Dissemination databases. We considered original studies, systematic reviews, economic evaluations, conference abstracts and posters. All collected data were recalculated to average annual cost per patient, expressed using the consumer price index for 2013 and converted to US dollars using purchasing power parity. Eight of the identified publications presented IC of PsA. Average annual IC per patient calculated using the friction cost approach range from US$1693.83 to $12,318.45, while using the human capital approach they range from US$1750.68 to $50,270.52. Result of the meta-analysis was a basis for calculating cost of work disability equaled US$10,754.04 per patient per year in 2013 prices. This systematic review revealed a great economic burden of the disease to the society. A small number of studies on IC in PsA justify further investigations.

Use of internal control T-cell populations in the flow cytometric evaluation for T-cell neoplasms.

PubMed

Hunt, Alicia M; Shallenberger, Wendy; Ten Eyck, Stephen P; Craig, Fiona E

2016-09-01

Flow cytometry is an important tool for identification of neoplastic T-cells, but immunophenotypic abnormalities are often subtle and must be distinguished from nonneoplastic subsets. Use of internal control (IC) T-cells in the evaluation for T-cell neoplasms was explored, both as a quality measure and as a reference for evaluating abnormal antigen expression. All peripheral blood specimens (3-month period), or those containing abnormal T-cells (29-month period), stained with CD45 V500, CD2 V450, CD3 PE-Cy7, CD7 PE, CD4 Per-CP-Cy5.5, CD8 APC-H7, CD56 APC, CD16&57 FITC, were evaluated. IC T-cells were identified (DIVA, BD Biosciences) and median fluorescence intensity (MFI) recorded. Selected files were merged and reference templates generated (Infinicyt, Cytognos). IC T-cells were present in all specimens, including those with abnormal T-cells, but subsets were less well-represented. IC T-cell CD3 MFI differed between instruments (p = 0.0007) and subsets (p < 0.001), but not specimen categories, and served as a longitudinal process control. Merged files highlighted small unusual IC-T subsets: CD2+(dim) (0.25% total), CD2- (0.03% total). An IC reference template highlighted neoplastic T-cells, but was limited by staining variability (IC CD3 MFI reference samples different from test (p = 0.003)). IC T-cells present in the majority of specimens can serve as positive and longitudinal process controls. Use of IC T-cells as an internal reference is limited by variable representation of subsets. Analysis of merged IC T-cells from previously analyzed patient samples can alert the interpreter to less-well-recognized non-neoplastic subsets. However, application of a merged file IC reference template was limited by staining variability. © 2016 Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Tuberculosis vaccine candidate: Characterization of H4-IC31 formulation and H4 antigen conformation.

PubMed

Deshmukh, Sasmit S; Magcalas, Federico Webster; Kalbfleisch, Kristen N; Carpick, Bruce W; Kirkitadze, Marina D

2018-08-05

Tuberculosis (TB) is one of the leading causes of death worldwide, making the development of effective TB vaccines a global priority. A TB vaccine consisting of a recombinant fusion protein, H4, combined with a novel synthetic cationic adjuvant, IC31 ® , is currently being developed. The H4 fusion protein consists of two immunogenic mycobacterial antigens, Ag85 B and TB10.4, and the IC31 ® adjuvant is a mixture of KLK, a leucine-rich peptide (KLKL5KLK), and the oligodeoxynucleotide ODN1a, a TLR9 ligand. However, efficient and robust methods for assessing these formulated components are lacking. Here, we developed and optimized phase analysis light scattering (PALS), electrical sensing zone (ESZ), and Raman, FTIR, and CD spectroscopy methods to characterize the H4-IC31 vaccine formulation. PALS-measured conductivity and zeta potential values could differentiate between the similarly sized particles of IC31 ® adjuvant and the H4-IC31 vaccine candidate and could thereby serve as a control during vaccine formulation. In addition, zeta potential is indicative of the adjuvant to antigen ratio which is the key in the immunomodulatory response of the vaccine. ESZ was used as an orthogonal method to measure IC31 ® and H4-IC31 particle sizes. Raman, FTIR, and CD spectroscopy revealed structural changes in H4 protein and IC31 ® adjuvant, inducing an increase in both the β-sheet and random coil content as a result of adsorption. Furthermore, nanoDSF showed changes in the tertiary structure of H4 protein as a result of adjuvantation to IC31 ® . Our findings demonstrate the applicability of biophysical methods to characterize vaccine components in the final H4-IC31 drug product without the requirement for desorption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Improving depiction of temporal bone anatomy with low-radiation dose CT by an integrated circuit detector in pediatric patients: a preliminary study.

PubMed

He, Jingzhen; Zu, Yuliang; Wang, Qing; Ma, Xiangxing

2014-12-01

The purpose of this study was to determine the performance of low-dose computed tomography (CT) scanning with integrated circuit (IC) detector in defining fine structures of temporal bone in children by comparing with the conventional detector. The study was performed with the approval of our institutional review board and the patients' anonymity was maintained. A total of 86 children<3 years of age underwent imaging of temporal bone with low-dose CT (80 kV/150 mAs) equipped with either IC detector or conventional discrete circuit (DC) detector. The image noise was measured for quantitative analysis. Thirty-five structures of temporal bone were further assessed and rated by 2 radiologists for qualitative analysis. κ Statistics were performed to determine the agreement reached between the 2 radiologists on each image. Mann-Whitney U test was used to determine the difference in image quality between the 2 detector systems. Objective analysis showed that the image noise was significantly lower (P<0.001) with the IC detector than with the DC detector. The κ values for qualitative assessment of the 35 fine anatomical structures revealed high interobserver agreement. The delineation for 30 of the 35 landmarks (86%) with the IC detector was superior to that with the conventional DC detector (P<0.05) although there were no differences in the delineation of the remaining 5 structures (P>0.05). The low-dose CT images acquired with the IC detector provide better depiction of fine osseous structures of temporal bone than that with the conventional DC detector.

Benefits and Costs of Improved Cookstoves: Assessing the Implications of Variability in Health, Forest and Climate Impacts

PubMed Central

Jeuland, Marc A.; Pattanayak, Subhrendu K.

2012-01-01

Current attention to improved cook stoves (ICS) focuses on the “triple benefits” they provide, in improved health and time savings for households, in preservation of forests and associated ecosystem services, and in reducing emissions that contribute to global climate change. Despite the purported economic benefits of such technologies, however, progress in achieving large-scale adoption and use has been remarkably slow. This paper uses Monte Carlo simulation analysis to evaluate the claim that households will always reap positive and large benefits from the use of such technologies. Our analysis allows for better understanding of the variability in economic costs and benefits of ICS use in developing countries, which depend on unknown combinations of numerous uncertain parameters. The model results suggest that the private net benefits of ICS will sometimes be negative, and in many instances highly so. Moreover, carbon financing and social subsidies may help enhance incentives to adopt, but will not always be appropriate. The costs and benefits of these technologies are most affected by their relative fuel costs, time and fuel use efficiencies, the incidence and cost-of-illness of acute respiratory illness, and the cost of household cooking time. Combining these results with the fact that households often find these technologies to be inconvenient or culturally inappropriate leads us to understand why uptake has been disappointing. Given the current attention to the scale up of ICS, this analysis is timely and important for highlighting some of the challenges for global efforts to promote ICS. PMID:22348005

NASA Team 2 Sea Ice Concentration Algorithm Retrieval Uncertainty

NASA Technical Reports Server (NTRS)

Brucker, Ludovic; Cavalieri, Donald J.; Markus, Thorsten; Ivanoff, Alvaro

2014-01-01

Satellite microwave radiometers are widely used to estimate sea ice cover properties (concentration, extent, and area) through the use of sea ice concentration (IC) algorithms. Rare are the algorithms providing associated IC uncertainty estimates. Algorithm uncertainty estimates are needed to assess accurately global and regional trends in IC (and thus extent and area), and to improve sea ice predictions on seasonal to interannual timescales using data assimilation approaches. This paper presents a method to provide relative IC uncertainty estimates using the enhanced NASA Team (NT2) IC algorithm. The proposed approach takes advantage of the NT2 calculations and solely relies on the brightness temperatures (TBs) used as input. NT2 IC and its associated relative uncertainty are obtained for both the Northern and Southern Hemispheres using the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) TB. NT2 IC relative uncertainties estimated on a footprint-by-footprint swath-by-swath basis were averaged daily over each 12.5-km grid cell of the polar stereographic grid. For both hemispheres and throughout the year, the NT2 relative uncertainty is less than 5%. In the Southern Hemisphere, it is low in the interior ice pack, and it increases in the marginal ice zone up to 5%. In the Northern Hemisphere, areas with high uncertainties are also found in the high IC area of the Central Arctic. Retrieval uncertainties are greater in areas corresponding to NT2 ice types associated with deep snow and new ice. Seasonal variations in uncertainty show larger values in summer as a result of melt conditions and greater atmospheric contributions. Our analysis also includes an evaluation of the NT2 algorithm sensitivity to AMSR-E sensor noise. There is a 60% probability that the IC does not change (to within the computed retrieval precision of 1%) due to sensor noise, and the cumulated probability shows that there is a 90% chance that the IC varies by less than +/-3%. We also examined the daily IC variability, which is dominated by sea ice drift and ice formation/melt. Daily IC variability is the highest, year round, in the MIZ (often up to 20%, locally 30%). The temporal and spatial distributions of the retrieval uncertainties and the daily IC variability is expected to be useful for algorithm intercomparisons, climate trend assessments, and possibly IC assimilation in models.

Studies of new media radiation induced laser. Final Report, 1 February 1979-30 April 1984

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

Han, K.S.; Shiu, Y.J.; Raju, S.R.

Various lasants were investigated especially, 2-iodohepafluoropropane (i-C3F7I) for the direct solar pumped lasers. Optical pumping of iodine laser was achieved using a small flashlamp. Using i-C3F7I as a laser gain medium, threshold inversion density, small signal gain, and laser performance at the elevated temperature were measured. The experimental results and analysis are presented. The iodine laser kinetics of the C3F7I and IBr system were numerically simulated. The concept of a direct solar-pumped laser amplifier using (i-C3F7I) as the laser material was evaluated and several kinetic coefficients for i-C3F7I laser system were reexamined. The results are discussed.

Naming it 'nano': Expert views on 'nano' terminology in informed consent forms of first-in-human nanomedicine trials.

PubMed

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

2016-04-01

Obtaining valid informed consent (IC) can be challenging in first-in-human (FIH) trials in nanomedicine due to the complex interventions, the hype and hope concerning potential benefits, and fear of harms attributed to 'nano' particles. We describe and analyze the opinions of expert stakeholders involved in translational nanomedicine regarding explicit use of 'nano' terminology in IC documents. We draw on content analysis of 46 in-depth interviews with European and North American stakeholders. We received a spectrum of responses (reluctance, ambivalence, absolute insistence) on explicit mention of 'nano' in IC forms with underlying reasons. We conclude that consistent, clear and honest communication regarding the 'nano' dimension of investigational product is critical in IC forms of FIH trials.

Demonstration of a specific C3a receptor on guinea pig platelets

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

Fukuoka, Y.; Hugli, T.E.

1988-05-15

Guinea pig platelets reportedly contain receptors specific for the anaphylatoxin C3a based on both ligand-binding studies and functional responses. A portion of the human 125I-C3a that binds to guinea pig platelets is competitively displaced by excess unlabeled C3a; however, the majority of ligand uptake was nonspecific. Uptake of 125I-C3a by guinea pig platelets is maximal in 1 min, and stimulation of guinea pig platelets by thrombin, ADP, or the Ca2+ ionophore A23187 showed little influence on binding of the ligand. Scatchard analysis indicated that approximately 1200 binding sites for C3a exist per cell with an estimated Kd of 8 xmore » 10(-10) M. Human C3a des Arg also binds to guinea pig platelets, but Scatchard analysis indicated that no specific binding occurred. Because the ligand-binding studies were complicated by high levels of nonspecific uptake, we attempted to chemically cross-link the C3a molecule to a specific component on the platelet surface. Cross-linkage of 125I-C3a to guinea pig platelets with bis(sulfosuccinimidyl)suberate revealed radioactive complexes at 105,000 and 115,000 m.w. on SDS-PAGE gels by autoradiographic analysis. In the presence of excess unlabeled C3a, complex formation was inhibited. No cross-linkage could be demonstrated between the inactive 125I-C3a des Arg and the putative C3a-R on guinea pig platelets. Human C3a, but not C3a des Arg induces serotonin release and aggregation of the guinea pig platelets. Human C3a was unable to induce either serotonin release or promote aggregation of human platelets. Uptake of human 125I-C3a by human platelets was not saturable, and Scatchard analysis was inconclusive. Attempts to cross-link 125I-C3a to components on the surface of human platelets also failed to reveal a ligand-receptor complex. Therefore, we conclude that guinea pig platelets have specific surface receptors to C3a and that human platelets appear devoid of receptors to the anaphylatoxin.« less

[Deliberate interruptions and changes of dose of inhaled corticosteroids by asthma patients: "a community pharmacy study"].

PubMed

Laforest, L; Van Ganse, É; Devouassoux, G; Chatté, G; Tamberou, C; Belhassen, M; Chamba, G

2015-01-01

Adherence to inhaled corticosteroids (ICS) remains a major issue for asthma management, even among patients receiving a regular prescription from their doctor. The frequency of deliberate interruption of ICS, and of spontaneous changes of dose, were studied in a population of asthma patients recruited in community pharmacies. Asthma patients (aged 18-50) recruited in community pharmacies reported in self-administered questionnaires their spontaneous interruptions and changes of doses of ICS during the past 3 months. The characteristics of patients who interrupted their therapy or who modified the dose were compared with other patients. The studied population included 252 patients (mean age 35 year-old, females: 59%), of whom 62% had inadequately controlled asthma. Among these patients, 25% had interrupted ICS therapy during the past 3 months, while 21% spontaneously changed the dose. The most reported reason for interrupting ICS was the cessation of symptoms (50%). In multivariate analysis, interrupting ICS was mainly associated with inadequate asthma control (OR=3.1, 95% CI 1.5-6.4), while the strongest association with changing ICS doses was the patients' perception of asthma as a concern in their lives (OR=3.2, 95% CI 1.2-8.4). These results underline a poor understanding of the purpose of ICS therapy by patients. They also highlight the need of therapeutic education to improve the management of the disease. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults

PubMed Central

Linzarini, Adriano; Dollfus, Sonia; Etard, Olivier; Orliac, François; Houdé, Olivier

2018-01-01

Abstract Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the “common variant–small effect” model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores. PMID:29527565

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults.

PubMed

Tissier, Cloélia; Linzarini, Adriano; Allaire-Duquette, Geneviève; Mevel, Katell; Poirel, Nicolas; Dollfus, Sonia; Etard, Olivier; Orliac, François; Peyrin, Carole; Charron, Sylvain; Raznahan, Armin; Houdé, Olivier; Borst, Grégoire; Cachia, Arnaud

2018-01-01

Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the "common variant-small effect" model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores.

Using NCAP to predict RFI effects in linear bipolar integrated circuits

NASA Astrophysics Data System (ADS)

Fang, T.-F.; Whalen, J. J.; Chen, G. K. C.

1980-11-01

Applications of the Nonlinear Circuit Analysis Program (NCAP) to calculate RFI effects in electronic circuits containing discrete semiconductor devices have been reported upon previously. The objective of this paper is to demonstrate that the computer program NCAP also can be used to calcuate RFI effects in linear bipolar integrated circuits (IC's). The IC's reported upon are the microA741 operational amplifier (op amp) which is one of the most widely used IC's, and a differential pair which is a basic building block in many linear IC's. The microA741 op amp was used as the active component in a unity-gain buffer amplifier. The differential pair was used in a broad-band cascode amplifier circuit. The computer program NCAP was used to predict how amplitude-modulated RF signals are demodulated in the IC's to cause undesired low-frequency responses. The predicted and measured results for radio frequencies in the 0.050-60-MHz range are in good agreement.

Posterior insular cortex - a site of vestibular-somatosensory interaction?

PubMed

Baier, Bernhard; Zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-09-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact.

In-service testing of Ni{sub 3}Al coupons and trays in carburizing furnaces at Delphi Saginaw. CRADA final report

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

Sikka, V.K.; Santella, M.L.; Viswanathan, S.

1998-08-01

This Cooperative Research and Development Agreement (CRADA) report deals with the development of nickel aluminide alloy for improved longer life heat-resistant fixture assemblies for batch and continuous pusher carburizing furnaces. The nickel aluminide development was compared in both coupon and component testing with the currently used Fe-Ni-Cr heat-resisting alloy known as HU. The specific goals of the CRADA were: (1) casting process development, (2) characterization and possible modification of the alloy composition to optimize its manufacturing ability and performance under typical furnace operating conditions, and (3) testing and evaluation of specimens and prototype fixtures. In support of the CRADA objectives,more » coupons of nickel aluminide and the HU alloy were installed in both batch and pusher furnaces. The coupons were taken from two silicon levels and contained welds made with two different filler compositions (IC-221LA and IC-221W). Both nickel-aluminide and HU coupons were removed from the batch and pusher carburizing furnace at time intervals ranging from one month to one year. The exposed coupons were cut and mounted for metallographic, hardness, and microprobe analysis. The results of the microstructural analysis have been transmitted to General Motors Corporation, Saginaw Division (Delphi Saginaw) through reports that were presented at periodic CRADA review meetings. Based on coupon testing and verification of the coupon results with the testing of trays, Delphi Saginaw moved forward with the use of six additional trays in a batch furnace and two assemblies in a pusher furnace. Fifty percent of the trays and fixtures are in the as-cast condition and the remaining trays and fixtures are in the preoxidized condition. The successful operating experience of two assemblies in the pusher furnace for nearly a year formed the basis for a production run of 63 more assemblies. The production run required melting of 94 heats weighing 500 lb. each. Twenty-six of the 94 heats were from virgin stock, and 68 were from the revert that used 50% virgin and 50% revert. Detailed chemical analysis of the 94 heats reflected that the nickel aluminide can be cast into heat-treat fixtures under production conditions. In addition to the chemical analysis, the castings showed excellent dimensional reproducibility. A total of six batch furnace trays and 65 pusher furnace assemblies of nickel aluminide alloy IC-221M are currently operating in production furnaces at Delphi Saginaw. Two of the pusher furnace assemblies have completed two years of service without any failure. The CRADA has accomplished the goal of demonstrating that the nickel aluminide can be produced under commercial production conditions and it has superior performance over the currently used HU alloy in both batch and pusher furnaces.« less

Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in Tel Aviv, 1998-2008.

PubMed

Mor, Z; Kolb, H; Lidji, M; Migliori, Gb; Leventhal, A

2013-03-21

Non-national migrants have limited access to medical therapy. This study compares diagnostic delay and treatment outcomes of non-insured non-national migrants (NINNM) with insured Israeli citizens (IC) in the Tel Aviv tuberculosis (TB) clinic between 1998 and 2008. Patient delay was the time from symptoms onset to doctor's visit, while system delay was measured from doctor visit to anti-TB therapy administration. We randomly sampled 222 NINNM and 265 IC. NINNM were younger than IC, had lower male to female ratio and fewer smoked. They had less drug/alcohol abuse, more cavitations on chest radiography, longer patient and shorter system delay. Mean patient and system delays of all patients were 25 ± 14 and 79 ± 42 days, respectively. In multivariate analysis, being NINNM, asymptomatic or smoking predicted longer patient delay, while being asymptomatic or having additional co-morbidity predicted longer system delay. Treatment success in sputum smear-positive pulmonary TB NINNM was 81% and 95.7% in IC (p=0.01). Treatment success was not associated with patient or system delay. In multivariate analysis, work security and treatment adherence predicted treatment success. NINNM had longer patient delay and worse therapy outcome, while IC had longer system delay. Both delays should be reduced. NINNM should be informed that TB therapy is free and unlinked with deportation.

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

NASA Astrophysics Data System (ADS)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

Optimizing methods for linking cinematic features to fMRI data.

PubMed

Kauttonen, Janne; Hlushchuk, Yevhen; Tikka, Pia

2015-04-15

One of the challenges of naturalistic neurosciences using movie-viewing experiments is how to interpret observed brain activations in relation to the multiplicity of time-locked stimulus features. As previous studies have shown less inter-subject synchronization across viewers of random video footage than story-driven films, new methods need to be developed for analysis of less story-driven contents. To optimize the linkage between our fMRI data collected during viewing of a deliberately non-narrative silent film 'At Land' by Maya Deren (1944) and its annotated content, we combined the method of elastic-net regularization with the model-driven linear regression and the well-established data-driven independent component analysis (ICA) and inter-subject correlation (ISC) methods. In the linear regression analysis, both IC and region-of-interest (ROI) time-series were fitted with time-series of a total of 36 binary-valued and one real-valued tactile annotation of film features. The elastic-net regularization and cross-validation were applied in the ordinary least-squares linear regression in order to avoid over-fitting due to the multicollinearity of regressors, the results were compared against both the partial least-squares (PLS) regression and the un-regularized full-model regression. Non-parametric permutation testing scheme was applied to evaluate the statistical significance of regression. We found statistically significant correlation between the annotation model and 9 ICs out of 40 ICs. Regression analysis was also repeated for a large set of cubic ROIs covering the grey matter. Both IC- and ROI-based regression analyses revealed activations in parietal and occipital regions, with additional smaller clusters in the frontal lobe. Furthermore, we found elastic-net based regression more sensitive than PLS and un-regularized regression since it detected a larger number of significant ICs and ROIs. Along with the ISC ranking methods, our regression analysis proved a feasible method for ordering the ICs based on their functional relevance to the annotated cinematic features. The novelty of our method is - in comparison to the hypothesis-driven manual pre-selection and observation of some individual regressors biased by choice - in applying data-driven approach to all content features simultaneously. We found especially the combination of regularized regression and ICA useful when analyzing fMRI data obtained using non-narrative movie stimulus with a large set of complex and correlated features. Copyright © 2015. Published by Elsevier Inc.

Second Breakdown of 18V Grounded Gate NMOS induced by the Kirk Effect under Electrostatic Discharge

NASA Astrophysics Data System (ADS)

Jeon, Byung-Chul; Lee, Seung-Chul; Han, Min-Koo

2003-09-01

Electrostatic Discharge (ESD) failure mechanisms of 18V grounded gate NMOS (GGNMOS) for liquid crystal display driver IC (LDI) applications are investigated and effects of layout design parameters on the ESD immunity level are analyzed. Experimental results show that 18V GGNMOS exhibits snapback characteristics and the ESD immunity level is rather high when XO (N-drift overlap over n+ source/drain) is sufficiently large, while GGNMOS does not exhibit the sustaining region and is very vulnerable to ESD stress when XO is relatively small. Simulation results show that the ESD failure mechanism of 18V GGNMOS could be the low-temperature second breakdown induced by the Kirk effect. It is inferred that a certain amount of XO is indispensable to ensure snapback characteristics and high ESD immunity level. Simulation results also show that the ESD immunity level is increased as drain contact to gate space (DCGS) is increased.

Cost-minimization analysis of imipenem/cilastatin versus meropenem in moderate to severe infections at a tertiary care hospital in Saudi Arabia.

PubMed

Joosub, Imraan; Gray, Andy; Crisostomo, Analyn; Salam, Abdul

2015-11-01

The aim of this study was to compare the costs of management of moderate to severe infections in patients treated with imipenem/cilastatin (IC) and meropenem (MEM). Pharmacoeconomic studies in Saudi Arabia are scarce. The current hospital formulary contains 2 carbapenems: IC and MEM. These antibiotics share a similar spectrum of activity. There are conflicting reviews with regard to the relative cost-effectiveness of these two agents. A retrospective, single-centre cohort study of 88 patients of IC versus MEM in moderate to severe infections was performed, applying cost-minimization analysis (CMA) methods. In accordance with CMA methods, the assumption of equivalent efficacy was first demonstrated by literature retrieved and appraised. Adult patients (⩾18 years old) diagnosed with moderate to severe infections, including skin and skin structure infections (SSIs), sepsis, intra-abdominal infections (IAIs), respiratory tract infections, urinary tract infections (UTIs) and hospital-acquired infections (HAIs), who were prescribed IC 500 mg every six hours intravenously (2 g per day) or MEM 1 g every eight hours (3 g per day), were included in the study. Only direct costs related to the management of the infections were included, in accordance with a payer perspective. Overall there was no difference in the mean total daily costs between IC (SAR 4784.46, 95% CI 4140.68, 5428.24) and MEM (4390.14, 95% CI 3785.82, 4994.45; p = 0.37). A significantly lower medicine acquisition cost per vial of IC was observed when compared to MEM, however there was a significantly higher cost attached to administration sets used in the IC group than the MEM group. Consultation, nursing and physician costs were not significantly different between the groups. No differences were observed in costs associated with adverse drug events (ADEs). This study has shown that while acquisition costs of IC at a dose of 500 mg q6 h may be lower than for MEM 1 g q8 h, mean total costs per day were not significantly different between IC and MEM, indicating that medicine costs are only a small element of the overall costs of managing moderate to severe infections.

Role of ictal baseline shifts and ictal high-frequency oscillations in stereo-electroencephalography analysis of mesial temporal lobe seizures.

PubMed

Wu, Shasha; Kunhi Veedu, Hari Prasad; Lhatoo, Samden D; Koubeissi, Mohamad Z; Miller, Jonathan P; Lüders, Hans O

2014-05-01

To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. There was no significant difference in all groups (P > 0.05). IC + RT + AC group had heavier acute toxicity effects than other groups, but it did not affect the treatment process, all patients could be tolerated. This retrospective study has demonstrated that alternating Chemo-radiotherapy and early radiotherapy not only can improve the survival rate for locally Advanced Nasopharyngeal Carcinoma, but also have slight toxicities and side reaction, all patients may tolerated.

Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.

PubMed

Martin, Judith M; Macias-Parra, Mercedes; Mudry, Peter; Conte, Umberto; Yan, Jean L; Liu, Ping; Capparella, M Rita; Aram, Jalal A

2017-01-01

Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited. Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored. Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established. Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.

Predictors of dynamic hyperinflation during the 6-minute walk test in stable chronic obstructive pulmonary disease patients

PubMed Central

Chen, Rui; Lin, Lin; Tian, Jing-Wei; Zeng, Bin; Zhang, Lei

2015-01-01

Background Dynamic hyperinflation (DH) is a major contributor to exercise limitation in chronic obstructive pulmonary disease (COPD). Therefore, we aimed to elucidate the physiological factors responsible for DH development during the 6-minute walk test (6MWT) in COPD patients and compare ventilatory response to the 6MWT in hyperinflators and non-hyperinflators. Methods A total of 105 consecutive subjects with stable COPD underwent a 6MWT, and the Borg dyspnea scale, oxygen saturation (SpO2), breathing pattern, and inspiratory capacity (IC) were recorded before and immediately after walking. The change in IC was measured, and subjects were divided into hyperinflators (ΔIC >0.0 L) and non-hyperinflators (ΔIC ≤0.0 L). Spirometry, the Modified Medical Research Council (MMRC) dyspnea scale and St George’s Respiratory Questionnaire (SGRQ) were also assessed. Results DH was present in 66.67% of subjects. ΔIC/IC was significantly and negatively correlated with the small airway function. On multiple stepwise regression analysis forced expiratory flow after exhaling 50% of the forced vital capacity (FEF50%) was the only predictor of ΔIC/IC. Non-hyperinflators had a higher post-walking VT (t=2.419, P=0.017) and post-walking VE (t=2.599, P=0.011) than the hyperinflators did. Age and resting IC were independent predictors of the 6-minute walk distance (6MWD) in hyperinflators. Conclusions DH was considerably common in subjects with COPD. Small airway function may partly contribute to the DH severity during walking. The ventilator response to the 6MWT differed between hyperinflators and non-hyperinflators. Resting hyperinflation is an important predictor of functional exercise capacity in hyperinflators. PMID:26380729

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

PubMed

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

Correlation between in vitro and in vivo antimalarial activity of compounds using CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and CQ-resistant strain of P. yoelii.

PubMed

Srivastava, Kumkum; Agarwal, Pooja; Soni, Awakash; Puri, S K

2017-07-01

Present efforts have been made to establish a correlation between in vitro and in vivo antimalarial activity using MIC, IC 50 and IC 90 values against CQ-sensitive (3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity against Plasmodium yoelii. The method of discriminant function analysis (DFA) was applied to analyze the data. It was observed that in vitro IC 90 values against both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative activity. The respective IC 50 and IC 90 values of compounds, which cured mice (i.e., animals did not show recrudescence of parasitemia even after 60 days posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum. Whereas the IC 50 and IC 90 values of compounds which exhibited in vivo suppressive activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively, against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P. falciparum. The findings suggest that IC 90 values against both 3D7 and K1 strains (p < 0.02) are the main contributors for the prediction of in vivo curative activity of a new molecule. Apart from this, a reasonable correlation between MIC and IC 50 values of compounds has also been established.

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

PubMed

Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

2012-06-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

Informal caregivers experience of supplemental oxygen in pulmonary fibrosis.

PubMed

Graney, Bridget A; Wamboldt, Frederick S; Baird, Susan; Churney, Tara; Fier, Kaitlin; Korn, Marjorie; McCormick, Mark; Vierzba, Thomas; Swigris, Jeffrey J

2017-07-01

Patients prescribed supplemental oxygen (O 2 ) therapy face challenges as they adjust to being constantly "tethered" to an oxygen delivery device. Informal caregivers (ICs) of patients with pulmonary fibrosis (PF) face their own, often overlooked hardships when O 2 is brought into their home and added to their lives. Our aim was to understand the multiple effects of supplemental oxygen therapy on ICs of patients with PF. We conducted single, semi-structured telephone interviews with twenty ICs of patients with PF who were using O 2 for at least 8 months. We performed a qualitative, content analysis based in grounded theory to examine data across subjects. ICs initially reacted to O 2 with trepidation and sadness as they came to recognize the changes it would cause in the lives of their patient-loved one (PLO). ICs recognized both beneficial and negative effects of O 2 on their PLOs. ICs also realized that O 2 created significant changes in their own lives, including introducing new roles and responsibilities for them, altering their home environments and significantly impacting their relationships with their PLOs. Although O 2 was a tangible and constant reminder of disease progression, over time ICs were able to adapt and accept their new lives with O 2 . ICs of patients with PF experience many life changes when their PLO is prescribed O 2 . Having O 2 prescribers anticipate and recognize these challenges provides an opportunity to give support and guidance to ICs of PF patients who require O 2 in the hopes of limiting the negative impact of O 2 on their lives. Clinicaltrials.gov , registration number NCT01961362 . Registered 9 October 2013.

Impact of Integrated Care Model (ICM) on Direct Medical Costs in Management of Advanced Chronic Obstructive Pulmonary Disease (COPD)

PubMed Central

Bandurska, Ewa; Damps-Konstańska, Iwona; Popowski, Piotr; Jędrzejczyk, Tadeusz; Janowiak, Piotr; Świętnicka, Katarzyna; Zarzeczna-Baran, Marzena; Jassem, Ewa

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is a commonly diagnosed condition in people older than 50 years of age. In advanced stage of this disease, integrated care (IC) is recommended as an optimal approach. IC allows for holistic and patient-focused care carried out at the patient’s home. The aim of this study was to analyze the impact of IC on costs of care and on demand for medical services among patients included in IC. Material/Methods The study included 154 patients diagnosed with advanced COPD. Costs of care (general, COPD, and exacerbations-related) were evaluated for 1 year, including 6-months before and after implementing IC. The analysis included assessment of the number of medical procedures of various types before and after entering IC and changes in medical services providers. Results Direct medical costs of standard care in advanced COPD were 886.78 EUR per 6 months. Costs of care of all types decreased after introducing IC. Changes in COPD and exacerbation-related costs were statistically significant (p=0.012492 and p=0.017023, respectively). Patients less frequently used medical services for respiratory system and cardiovascular diseases. Similarly, the number of hospitalizations and visits to emergency medicine departments decreased (by 40.24% and 8.5%, respectively). The number of GP visits increased after introducing IC (by 7.14%). Conclusions The high costs of care in advanced COPD indicate the need for new forms of effective care. IC caused a decrease in costs and in the number of hospitalization, with a simultaneous increase in the number of GP visits. PMID:28603270

What can we learn from sediment connectivitiy indicies regarding natural hazard processes in torrent catchments?

NASA Astrophysics Data System (ADS)

Schmutz, Daria; Zimmermann, Markus; Keiler, Margreth

2017-04-01

Sediment connectivity is defined as the degree of coupling between sediment sources and sinks in a system and describes the effectiveness of the transfer of sediment from hillslopes into channels and within channels (Bracken et al. 2015). Borselli et al. (2008) developed a connectivity index (IC) based on digital terrain models (DTMs). Cavalli et al. (2013) adapted this index for mountainous catchments. These measures of connectivity provide overall information about connectivity pattern in the catchment, thus the understanding of sediment connectivity can help to improve the hazard analysis in these areas. Considering the location of settlements in the alpine regions, high sediment transfer can pose a threat to villages located nearby torrents or at the debris cones. However, there is still a lack of studies on the linkage between IC and hazardous events with high sediment yield in alpine catchments. In this study, the expressiveness and applicability of IC is tested in relation with hazardous events in several catchments of the Bernese and Pennine Alps (Switzerland). The IC is modelled based on DTMs (resolution 2 m or if available 0.5 m) indicating the surface from the time before and after a documented hazardous event and analysed with respect to changes in connectivity caused by the event. The spatial pattern of connectivity is compared with the observed sediment dynamic during the event using event documentations. In order to validate the IC, a semi-quantitative field connectivity index (FIC) is developed addressing characteristics of the channel, banks and slopes and applied in a selection of the case studies. First analysis shows that the IC is highly sensitive to the resolution and quality of the DTM. Connectivity calculated by the IC is highest along the channel. The general pattern of connectivity is comparable applying the IC for the DTM before and after the event. Range of the connectivity values gained from IC modelling is highly specific for each study area and so are their changes by the events. Whereas some slopes show an increased connectivity, others are less connected or not affected according to the IC. Further results of the comparison between the FIC and the IC and an evaluation of both indices in the context of hazardous events will be presented. REFERENCES Borselli, L., Cassi, P. & Torri, D. 2008: Prolegomena to sediment and flow connectivity in the landscape. A GIS and field numerical assessment. CATENA 75 (3), 268-277. Bracken, L. J., Turnbull, L., Wainwright, J. & Bogaart, P. 2015: Sediment connectivity. A framework for understanding sediment transfer at multiple scales. Earth Surface Processes and Landforms 40 (2), 177-188. Cavalli, M., Trevisani, S., Comiti, F. & Marchi, L. 2013: Geomorphometric assessment of spatial sediment connectivity in small Alpine catchments. Geomorphology 188, 31-41.

Massively Parallel, Molecular Analysis Platform Developed Using a CMOS Integrated Circuit With Biological Nanopores

PubMed Central

Roever, Stefan

2012-01-01

A massively parallel, low cost molecular analysis platform will dramatically change the nature of protein, molecular and genomics research, DNA sequencing, and ultimately, molecular diagnostics. An integrated circuit (IC) with 264 sensors was fabricated using standard CMOS semiconductor processing technology. Each of these sensors is individually controlled with precision analog circuitry and is capable of single molecule measurements. Under electronic and software control, the IC was used to demonstrate the feasibility of creating and detecting lipid bilayers and biological nanopores using wild type α-hemolysin. The ability to dynamically create bilayers over each of the sensors will greatly accelerate pore development and pore mutation analysis. In addition, the noise performance of the IC was measured to be 30fA(rms). With this noise performance, single base detection of DNA was demonstrated using α-hemolysin. The data shows that a single molecule, electrical detection platform using biological nanopores can be operationalized and can ultimately scale to millions of sensors. Such a massively parallel platform will revolutionize molecular analysis and will completely change the field of molecular diagnostics in the future.

Posterior pharyngeal candidiasis in the absence of clinically overt oral involvement: a cross-sectional study.

PubMed

Glavey, Siobhan V; Keane, Niamh; Power, Maria; O'Regan, Anthony W

2013-12-01

Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. Median age was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS, and 20 % of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at bronchoscopy, even in the absence of clinically overt oral involvement.

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program

PubMed Central

Chiu, Sherry Yueh-Hsia; Chuang, Shu-Ling; Chen, Sam Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chang, Dun-Cheng; Lee, Yi-Chia; Wu, Ming-Shiang; Chou, Chu-Kuang; Hsu, Wen-Feng; Chiou, Shu-Ti; Chiu, Han-Mo

2017-01-01

Objectives Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. Design From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. Results One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (μg Hb/g faeces) (100–149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. Conclusions Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC. PMID:26515543

Pyrolysis characteristics of integrated circuit boards at various particle sizes and temperatures.

PubMed

Chiang, Hung-Lung; Lin, Kuo-Hsiung; Lai, Mei-Hsiu; Chen, Ting-Chien; Ma, Sen-Yi

2007-10-01

A pyrolysis method was employed to recycle the metals and brominated compounds blended into printed circuit boards. This research investigated the effect of particle size and process temperature on the element composition of IC boards and pyrolytic residues, liquid products, and water-soluble ionic species in the exhaust, with the overall goal being to identify the pyrolysis conditions that will have the least impact on the environment. Integrated circuit (IC) boards were crushed into 5-40 mesh (0.71-4.4mm), and the crushed particles were pyrolyzed at temperatures ranging from 200 to 500 degrees C. The thermal decomposition kinetics were measured by a thermogravimetric (TG) analyzer. The composition of pyrolytic residues was analyzed by Energy Dispersive X-ray Spectrometer (EDS), Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In addition, the element compositions of liquid products were analyzed by ICP-AES and ICP-MS. Pyrolytic exhaust was collected by a water-absorption system in an ice-bath cooler, and IC analysis showed that the absorbed solution comprised 11 ionic species. Based on the pyrolytic kinetic parameters of TG analysis and pyrolytic residues at various temperatures for 30 min, the effect of particle size was insignificant in this study, and temperature was the key factor for the IC board pyrolysis. Two stages of decomposition were found for IC board pyrolysis under nitrogen atmosphere. The activation energy was 38-47 kcal/mol for the first-stage reaction and 5.2-9.4 kcal/mol for the second-stage reaction. Metal content was low in the liquid by-product of the IC board pyrolysis process, which is an advantage in that the liquid product could be used as a fuel. Brominate and ammonium were the main water-soluble ionic species of the pyrolytic exhaust. A plan for their safe and effective disposal must be developed if the pyrolytic recycling process is to be applied to IC boards.

A New Highly Selective and Specific Anti-puerarin polyclonal Antibody for Determination of Puerarin Using a Mannich Reaction Hapten Conjugate

PubMed Central

Udomsin, Orapin; Krittanai, Supaluk; Kitisripanya, Tharita; Tanaka, Hiroyuki; Putalun, Waraporn

2017-01-01

Background: Puerarin (PUE) is a phytoestrogen found in Pueraria candollei and Pueraria lobata. These plants are substantial for traditional medicine in various Asian countries. PUE is a key marker that can be found only in the Pueraria species. Objective: To establish the method for determination of PUE content which is required for quality control of pharmaceutical products. Materials and Methods: PUE-cationized bovine serum albumin conjugate was created via Mannich reaction. After the rabbit immunization, the obtain anti-PUE polyclonal antibody (PAb) was used to develop an enzyme-linked immunosorbent assay (ELISA). Results: An anti-PUE PAb possess a great sensitivity and specificity. The cross-reactivity analysis shows no cross-reaction of an established antibody against other substances. In addition, we successfully developed an indirect competitive ELISA (icELISA) for the quantitative analysis of PUE. The result of method validation conforms to acceptance criteria and correlates with high-performance liquid chromatography, the reference method. The icELISA was applied to determine PUE content in Pueraria spp. plant samples and its derived pharmaceutical products. Conclusion: This highly specific immunogen was created from the Mannich reaction. An icELISA can also be applied to other research propose in the further studies. SUMMARY The new immunogen conjugated (puerarin-cBSA) via Mannich reaction was successfully in rising of antibody against puerarin (PUE)The obtained anti-PUE polyclonal antibody (PAb) was high sensitivity and specificity to PUEAn indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed and validated using anti-PUE PAbThe established icELISA was applied to determine PUE content in various tuberous root of Pueraria sppMoreover, icELISA method can be applicable in Pueraria spp. derived products. Abbreviations used: PUE: Puerarin; PAb: Polyclonal antibody; ELISA: Enzyme-linked immunosorbent assay; icELISA: Indirect competitive ELISA; cBSA: Cationized bovine serum albumin. PMID:29491643

Agreement between different methods and predictive equations for resting energy expenditure in overweight and obese Brazilian men.

PubMed

de Oliveira, Fernanda Cristina Esteves; Alves, Raquel Duarte Moreira; Zuconi, Carolina Pereira; Ribeiro, Andréia Queiroz; Bressan, Josefina

2012-09-01

Predictive equations and methods tend to overestimate or underestimate resting energy expenditure (REE) compared with indirect calorimetry (IC). This cross-sectional study aimed to evaluate the agreement between methods and equations for REE estimation of overweight and obese Brazilian men. Data from 48 healthy volunteers, ages 20 to 43 years and with body mass index ranging from 26.4 to 35.2, were collected between October 2008 and October 2009. REE was measured by IC, using Deltatrac (IC1) and KORR-MetaCheck (IC2) devices. It was estimated by bioelectrical impedance analysis (BIA) using tetrapolar (BIA1) and bipolar (BIA2) devices, and by the equations of Mifflin, World Health Organization/Food and Agriculture Organization/United Nations University, Fleisch, Horie-Waitzberg and Gonzalez, and Ireton-Jones. The association and agreement among the methods and equations were assessed by the interclass correlation coefficient, Bland-Altman analysis, and by the percentage of the difference between values obtained from the standard method and alternative methods and equations. Most methods showed high agreement with IC1. The highest agreements were found for Mifflin (-2.14%), Fleisch (-3.05%), Horie-Waitzberg and Gonzalez (4.41%), and BIA2 (5.25%). Similar results were shown by the Bland-Altman analyses. BIA2, followed by BIA1, Ireton-Jones, Mifflin, and Fleisch, showed the highest association with IC1. Thus, the Mifflin, Fleisch, Horie-Waitzberg and Gonzalez equations, and BIA2, were the most accurate methods for REE estimation in this study. However, because those equations have shown considerable variability, they should be used cautiously. In addition, the IC2 was not found to be an accurate method for REE estimation in overweight and obese men included in this study. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells

PubMed Central

Pannella, Micaela; Caliceti, Cristiana; Fortini, Francesca; Aquila, Giorgio; Sega, Francesco Vieceli Dalla; Pannuti, Antonio; Fortini, Cinzia; Morelli, Marco Bruno; Fucili, Alessandro; Francolini, Gloria; Voltan, Rebecca; Secchiero, Paola; Dinelli, GiovannI; Leoncini, Emanuela; Ferracin, Manuela; Hrelia, Silvana; Miele, Lucio; Rizzo, Paola

2017-01-01

It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = −0.526 and r = −0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. PMID:26987674

Update on Common-Cause Failure Experience and Mitigation Practices

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

Wood, Richard Thomas; Muhlheim, Michael David; Pullum, Laura L

2014-04-01

Experience in other industries has shown that digital technology can provide substantial benefits in terms of performance and reliability. However, the U.S. nuclear power industry has been slow to adopt the technology extensively in its instrumentation and control (I&C) applications because of inhibiting factors such as regulatory uncertainty, insufficient technological experience base, implementation complexity, limited availability of nuclear-qualified products and vendors, and inadequate definition of modernization cost recapture. Although there have been examples of digital technology usage in the nuclear power industry, challenges to the qualification of digital technology for high-integrity nuclear power plant (NPP) applications have severely constrained moremore » widespread progress in achieving the benefits that are possible through the transition to digital. The U.S. Department of Energy (DOE) Office of Nuclear Energy (NE) established the Advanced Sensors and Instrumentation (ASI) technology area under the Nuclear Energy Enabling Technologies (NEET) Program to coordinate the instrumentation and controls (I&C) research across DOE NE and to identify and lead efforts to address common needs. As part of the NEET ASI research program, the Digital Technology Qualification project was established. Under this project, the Oak Ridge National Laboratory (ORNL) is leading the investigation into mitigation of digital common-cause failure (CCF) vulnerabilities for nuclear-qualified applications. This technical report documents updated and expanded findings from research activities by ORNL. Specifically, the report describes CCF experience in the nuclear and nonnuclear industries, identifies the state of the practice for CCF mitigation through key examples, and presents conclusions from the determination of knowledge gaps.« less

The bolometric light curves and physical parameters of stripped-envelope supernovae

DOE PAGES

Prentice, S. J.; Mazzali, P. A.; Pian, E.; ...

2016-02-08

The optical and optical/near-infrared pseudo-bolometric light curves of 85 stripped-envelope supernovae (SNe) are constructed using a consistent method and a standard cosmology. The light curves are analysed to derive temporal characteristics and peak luminosity L p , enabling the construction of a luminosity function. Subsequently, the mass of 56 Ni synthesized in the explosion, along with the ratio of ejecta mass to ejecta kinetic energy, are found. Analysis shows that host-galaxy extinction is an important factor in accurately determining luminosity values as it is significantly greater than Galactic extinction in most cases. It is found that broad-lined SNe Ic (SNemore » Ic-BL) and gamma-ray burst SNe are the most luminous subtypes with a combined median L p , in erg s -1 , of log(L p) = 43.00 compared to 42.51 for SNe Ic, 42.50 for SNe Ib, and 42.36 for SNe IIb. It is also found that SNe Ic-BL synthesize approximately twice the amount of 56Ni compared with SNe Ic, Ib, and IIb, with median M Ni = 0.34, 0.16, 0.14, and 0.11 M ⊙ , respectively. SNe Ic-BL, and to a lesser extent SNe Ic, typically rise from L p /2 to L p more quickly than SNe Ib/IIb; consequently, their light curves are not as broad.« less

A New Interface for the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Koppers, A. A. P.; Tauxe, L.; Constable, C.; Shaar, R.; Jonestrask, L.

2014-12-01

The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of uploading data, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Data uploading has been simplified and no longer requires the use of the Excel SmartBook interface. Instead, properly formatted MagIC text files can be dragged-and-dropped onto an HTML 5 web interface. Data can be uploaded one table at a time to facilitate ease of uploading and data error checking is done online on the whole dataset at once instead of incrementally in an Excel Console. Searching the database has improved with the addition of more sophisticated search parameters and with the ability to use them in complex combinations. Searches may also be saved as permanent URLs for easy reference or for use as a citation in a publication. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. Data from the MagIC database may be downloaded from individual contributions or from online searches for offline use and analysis in the tab delimited MagIC text file format. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

Factors associated with vaginal birth after cesarean in a maternity hospital of Rio de Janeiro.

PubMed

d'Orsi, E; Chor, D; Giffin, K; Barbosa, G P; Angulo-Tuesta, A J; Gama, A S; Pessoa, L G; Shiraiwa, T; Fonseca, M J

2001-08-01

Identifying characteristics associated with vaginal birth after cesarean. Case-control study based on medical records. women with previous cesarean, who had delivered in a public Rio de Janeiro maternity hospital between 1992 and 1996. 141 cases (vaginal births after cesarean) and 304 controls (a new cesarean after other(s)). Multivariate analysis with logistic regression was carried out. The following characteristics were associated with greater probability of vaginal birth (IC=95%): only one previous cesarean (OR=19.05; IC=6.88-52.76); cervical dilatation at admission above 3 cm (OR=8.86; IC=4.93-15.94); gestational age below 37 weeks (OR=3.01; IC=1.40-6.46); history of at least one previous vaginal birth (OR=2.12; IC=1.18-3.82); level of education below high school (OR=1.94; IC=1.02-3.69). Chronic hypertension reduced the chances of vaginal birth (OR=0.44; IC=0.22-0.88). Among the factors that can be modified to reduce the number of repeated cesareans are: trial of labor promotion, reducing admission of women at early stages of labor and adequate hypertension management during pregnancy. Among the factors that can be modified to reduce the number of repeated cesareans are: the trial of labor promotion for women who present previous cesarean, reducing admission of women at early stages of labor and adequate hypertension management during pregnancy.

Assessing Treatment Effects of Inhaled Corticosteroids on Medical Expenses and Exacerbations among COPD Patients: Longitudinal Analysis of Managed Care Claims

PubMed Central

Akazawa, Manabu; Stearns, Sally C; Biddle, Andrea K

2008-01-01

Objective To assess costs, effectiveness, and cost-effectiveness of inhaled corticosteroids (ICS) augmenting bronchodilator treatment for chronic obstructive pulmonary disease (COPD). Data Sources Claims between 1997 and 2005 from a large managed care database. Study Design Individual-level, fixed-effects regression models estimated the effects of initiating ICS on medical expenses and likelihood of severe exacerbation. Bootstrapping provided estimates of the incremental cost per severe exacerbation avoided. Data Extraction Methods COPD patients aged 40 or older with ≥15 months of continuous eligibility were identified. Monthly observations for 1 year before and up to 2 years following initiation of bronchodilators were constructed. Principal Findings ICS treatment reduced monthly risk of severe exacerbation by 25 percent. Total costs with ICS increased for 16 months, but declined thereafter. ICS use was cost saving 46 percent of the time, with an incremental cost-effectiveness ratio of $2,973 per exacerbation avoided; for patients ≥50 years old, ICS was cost saving 57 percent of time. Conclusions ICS treatment reduces exacerbations, with an increase in total costs initially for the full sample. Compared with younger patients with COPD, patients aged 50 or older have reduced costs and improved outcomes. The estimated cost per severe exacerbation avoided, however, may be high for either group because of uncertainty as reflected by the large standard errors of the parameter estimates. PMID:18671750

Cortical Auditory Deafferentation Induces Long-Term Plasticity in the Inferior Colliculus of Adult Rats: Microarray and qPCR Analysis

PubMed Central

Clarkson, Cheryl; Herrero-Turrión, M. Javier; Merchán, Miguel A.

2012-01-01

The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs. PMID:23233834

Significant savings with a stepped care model for treatment of patients with intermittent claudication.

PubMed

Fokkenrood, H J P; Scheltinga, M R M; Koelemay, M J W; Breek, J C; Hasaart, F; Vahl, A C; Teijink, J A W

2014-10-01

International guidelines recommend supervised exercise therapy (SET) as primary treatment for intermittent claudication (IC). The aim of this study was to calculate treatment costs in patients with IC and to estimate nationwide annual savings if a stepped care model (SCM, primary SET treatment followed by revascularization in case of SET failure) was followed. Invoice data of all patients with IC in 2009 were obtained from a Dutch health insurance company (3.4 million members). Patients were divided into three groups based on initial treatment after diagnosis (t0). The SET group received SET initiated at any time between 12 months before and up to 3 months after t0. The intervention group (INT) underwent endovascular or open revascularization between t0 and t+3 months. The third group (REST) received neither SET nor any intervention. All peripheral arterial disease related invoices were recorded during 2 years and average costs per patient were calculated. Savings following use of a SCM were calculated for three scenarios. Data on 4954 patients were analyzed. Initial treatment was SET (n = 701, 14.1%), INT (n = 1363, 27.5%), or REST (n = 2890, 58.3%). Within 2 years from t0, invasive revascularization in the SET group was performed in 45 patients (6.4%). Additional interventions (primary at other location and/or re-interventions) were performed in 480 INT patients (35.2%). Some 431 REST patients received additional SET (n = 299, 10.3%) or an intervention (n = 132, 4.5%). Mean total IC related costs per patient were €2,191, €9851 and €824 for SET, INT, and REST, respectively. Based on a hypothetical worst, moderate, and best case scenario, some 3.8, 20.6, or 33.0 million euros would have been saved per annum if SCM was implemented in the Dutch healthcare system. Implementation of a SCM treatment for patients with IC may lead to significant savings of health care resources. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Collagen fragment biomarkers as serological biomarkers of lean body mass – a biomarker pilot study from the DAHANCA25B cohort and matched controls

PubMed Central

Nedergaard, Anders; Dalgas, Ulrik; Primdahl, Hanne; Johansen, Jørgen; Overgaard, Jens; Overgaard, Kristian; Henriksen, Kim; Karsdal, Morten Asser; Lønbro, Simon

2015-01-01

Background Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying success. Easily applicable serological biomarkers of lean and/or muscle mass and change therein would benefit monitoring of muscle mass during muscle atrophy as well as during recovery. We set out to validate if novel peptide biomarkers derived from Collagen III and VI were markers of lean body mass (LBM) or change therein in head and neck cancer patients in the Danish Head and Neck Cancer Group(DAHANCA) 25B cohort subjected to resistance training as well as in an age-matched and gender-matched control group. Methods Blood samples and dual X-ray absorptiometry data were measured at baseline, after 12 and 24 weeks in 41 HNSCC subjects of the DAHANCA 25B cohort of subjects recovering from neck and head cancer (stages provided in Table 1), and at baseline only in 21 healthy age-matched and gender-matched controls. Serum from blood was analyzed for the ProC3, IC6, and C6M peptide biomarkers and LBM were derived from the dual X-ray absorptiometry scans. Results We were not able to show any correlation between biomarkers and LBM or C6M and anabolic response to exercise in recovering head and neck cancer patients. However, we did find that the biomarkers IC6, IC6/C6M, and ProC3 are biomarkers of LBM in the control group subjects (R2/P of 0.249/0.035, 0.416/0.007 and 0.178 and P = 0.057, respectively), Conclusion In conclusion, the IC6, ProC3, and IC6/C6M biomarkers are indeed biomarkers of LBM in healthy individuals of both genders, but not in HNSCC patients. PMID:26673155

Spatiotemporal analysis of single-trial EEG of emotional pictures based on independent component analysis and source location

NASA Astrophysics Data System (ADS)

Liu, Jiangang; Tian, Jie

2007-03-01

The present study combined the Independent Component Analysis (ICA) and low-resolution brain electromagnetic tomography (LORETA) algorithms to identify the spatial distribution and time course of single-trial EEG record differences between neural responses to emotional stimuli vs. the neutral. Single-trial multichannel (129-sensor) EEG records were collected from 21 healthy, right-handed subjects viewing the emotion emotional (pleasant/unpleasant) and neutral pictures selected from International Affective Picture System (IAPS). For each subject, the single-trial EEG records of each emotional pictures were concatenated with the neutral, and a three-step analysis was applied to each of them in the same way. First, the ICA was performed to decompose each concatenated single-trial EEG records into temporally independent and spatially fixed components, namely independent components (ICs). The IC associated with artifacts were isolated. Second, the clustering analysis classified, across subjects, the temporally and spatially similar ICs into the same clusters, in which nonparametric permutation test for Global Field Power (GFP) of IC projection scalp maps identified significantly different temporal segments of each emotional condition vs. neutral. Third, the brain regions accounted for those significant segments were localized spatially with LORETA analysis. In each cluster, a voxel-by-voxel randomization test identified significantly different brain regions between each emotional condition vs. the neutral. Compared to the neutral, both emotional pictures elicited activation in the visual, temporal, ventromedial and dorsomedial prefrontal cortex and anterior cingulated gyrus. In addition, the pleasant pictures activated the left middle prefrontal cortex and the posterior precuneus, while the unpleasant pictures activated the right orbitofrontal cortex, posterior cingulated gyrus and somatosensory region. Our results were well consistent with other functional imaging studies, while revealed temporal dynamics of emotional processing of specific brain structure with high temporal resolution.

Comparison of multivariate analysis methods for extracting the paraffin component from the paraffin-embedded cancer tissue spectra for Raman imaging

NASA Astrophysics Data System (ADS)

Meksiarun, Phiranuphon; Ishigaki, Mika; Huck-Pezzei, Verena A. C.; Huck, Christian W.; Wongravee, Kanet; Sato, Hidetoshi; Ozaki, Yukihiro

2017-03-01

This study aimed to extract the paraffin component from paraffin-embedded oral cancer tissue spectra using three multivariate analysis (MVA) methods; Independent Component Analysis (ICA), Partial Least Squares (PLS) and Independent Component - Partial Least Square (IC-PLS). The estimated paraffin components were used for removing the contribution of paraffin from the tissue spectra. These three methods were compared in terms of the efficiency of paraffin removal and the ability to retain the tissue information. It was found that ICA, PLS and IC-PLS could remove the paraffin component from the spectra at almost the same level while Principal Component Analysis (PCA) was incapable. In terms of retaining cancer tissue spectral integrity, effects of PLS and IC-PLS on the non-paraffin region were significantly less than that of ICA where cancer tissue spectral areas were deteriorated. The paraffin-removed spectra were used for constructing Raman images of oral cancer tissue and compared with Hematoxylin and Eosin (H&E) stained tissues for verification. This study has demonstrated the capability of Raman spectroscopy together with multivariate analysis methods as a diagnostic tool for the paraffin-embedded tissue section.

Efficacy of intraoperative cell salvage in decreasing perioperative blood transfusion rates in first-time cardiac surgery patients: a retrospective study.

PubMed

Côté, Claudia L; Yip, Alexandra M; MacLeod, Jeffrey B; O'Reilly, Bill; Murray, Joshua; Ouzounian, Maral; Brown, Craig D; Forgie, Rand; Pelletier, Marc P; Hassan, Ansar

2016-09-01

Evidence regarding the safety and efficacy of intraoperative cell salvage (ICS) in transfusion reduction during cardiac surgery remains conflicting. We sought to evaluate the impact of routine ICS on outcomes following cardiac surgery. We conducted a retrospective analysis of patients who underwent nonemergent, first-time cardiac surgery 18 months before and 18 months after the implementation of routine ICS. Perioperative transfusion rates, postoperative bleeding, clinical and hematological outcomes, and overall cost were examined. We used multivariable logistic regression modelling to determine the risk-adjusted effect of ICS on likelihood of perioperative transfusion. A total of 389 patients formed the final study population (186 undergoing ICS and 203 controls). Patients undergoing ICS had significantly lower perioperative transfusion rates of packed red blood cells (pRBCs; 33.9% v. 45.3% p = 0.021), coagulation products (16.7% v. 32.5% p < 0.001) and any blood product (38.2% v. 52.7%, p = 0.004). Patients receiving ICS had decreased mediastinal drainage at 12 h (mean 320 [range 230-550] mL v. mean 400 [range 260-690] mL, p = 0.011) and increased postoperative hemoglobin (mean 104.7 ± 13.2 g/L v. 95.0 ± 11.9 g/L, p < 0.001). Following adjustment for other baseline and intraoperative covariates, ICS emerged as an independent predictor of lower perioperative transfusion rates of pRBCs (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31-0.87), coagulation products (OR 0.41, 95% CI 0.24-0.71) and any blood product (OR 0.47, 95% CI 0.29-0.77). Additionally, ICS was associated with a cost benefit of $116 per patient. Intraoperative cell salvage could represent a clinically cost-effective way of reducing transfusion rates in patients undergoing cardiac surgery. Further research on systematic ICS is required before recommending it for routine use.

Traditional and Improved Stove Use on Household Air Pollution and Personal Exposures in Rural Western Kenya

PubMed Central

Yip, Fuyuen; Christensen, Bryan; Sircar, Kanta; Naeher, Luke; Bruce, Nigel; Pennise, David; Lozier, Matthew; Pilishvili, Tamara; Loo, Jennifer; Stanistreet, Debbi; Nyagol, Ronald; Muoki, Justus; de Beer, Lindsey; Sage, Michael; Kapil, Vikas

2017-01-01

Background Over 40% of the world's population rely on solid fuels for heating and cooking. Use of improved biomass cookstoves (ICS) has the potential to reduce household air pollution (HAP). Objectives As part of an evaluation to identify ICS for use in Kenya, we collected indoor air and personal air samples to assess differences between traditional cookstoves (TCS) and ICS. Methods We conducted a cross-over study in 2012 in two Kenyan villages; up to six different ICS were installed in 45 households during six two-week periods. Forty-eight hour kitchen measurements of fine particulate matter (PM2.5) and carbon monoxide (CO) were collected for the TCS and ICS. Concurrent personal CO measurements were conducted on the mother and one child. We performed descriptive analysis and compared paired measurements between baseline (TCS only) and each ICS. Results The geometric mean of 48-hour baseline PM2.5 and CO concentrations in the kitchen was 586 μg/m3 (95% CI: 460, 747) and 4.9 ppm (95% CI: 4.3, 5.5), respectively. For each ICS, the geometric mean kitchen air pollutant concentration was lower than the TCS: median reductions were 38.8% (95% CI: 29.5, 45.2) for PM2.5 and 27.1% (95% CI: 17.4, 40.3) for CO, with statistically significant relationships for four ICS. We also observed a reduction in personal exposures with ICS use. Conclusions We observed a reduction in mean 48-hour PM2.5 and CO concentrations compared to the TCS; however, concentrations for both pollutants were still consistently higher than WHO Guidelines. Our findings illustrate that ICS tested in real-world settings can reduce exposures to HAP, but implementation of cleaner fuels and related stove technologies may also be necessary to optimize public health benefits. PMID:27923586

Characterization of cogon grass (Imperata cylindrica) pollen extract and preliminary analysis of grass group 1, 4 and 5 homologues using monoclonal antibodies to Phleum pratense.

PubMed

Kumar, L; Sridhara, S; Singh, B P; Gangal, S V

1998-11-01

Previous studies have established the role of Imperata cylindrica (Ic) pollen in type I allergic disorders. However, no systematic information is available on the allergen composition of Ic pollen extract. To characterize the IgE-binding proteins of Ic pollen extract and to detect the presence of grass group 1, 4 and 5 allergen homologues, if any. Pollen extract of Ic was analyzed by in vivo and in vitro procedures such as intradermal tests (ID), enzyme-linked immunosorbent assay (ELISA), ELISA-inhibition, thin-layer isoelectric focusing (TLIEF), sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Dot blot assay was carried out to check the presence of well-known group 1, 4, and 5 allergen homologues in Ic pollen extract. Out of 303 respiratory allergies patients skin-tested, 27 showed sensitivity to Ic pollen extract. Specific IgE levels were elevated in all 15 serum samples tested. The extract prepared for this study was found to be highly potent since it required only 400 ng of homologous proteins for 50% inhibition of binding in ELISA inhibition assays. TLIEF of Ic pollen extract showed 44 silver-stained bands (pI 3.5-7.0) while SDS-PAGE resolved it into 24 Coomassie-Brilliant-Blue-stained bands (MW 100-10 kD). Immunoblotting with individual patient sera recognized 7 major IgE-binding bands (MW 85, 62, 57, 43, 40, 28 and 16 kD) in Ic pollen extract. A panel of monoclonal antibodies, specific to group 1, 4 and 5 allergens from Phleum pratense pollen extract identified group 5 and group 4 homologues in Ic pollen extract. Ic pollen extract was characterized for the protein profile by TLIEF and SDS-PAGE. IgE reactivity was determined by ELISA and immunoblot. Monoclonal antibodies to group 5 and group 4 allergens reacted weakly showing that this pollen contains group 5 and group 4 homologous allergens.

Assessment of traditional and improved stove use on household air pollution and personal exposures in rural western Kenya.

PubMed

Yip, Fuyuen; Christensen, Bryan; Sircar, Kanta; Naeher, Luke; Bruce, Nigel; Pennise, David; Lozier, Matthew; Pilishvili, Tamara; Loo Farrar, Jennifer; Stanistreet, Debbi; Nyagol, Ronald; Muoki, Justus; de Beer, Lindsey; Sage, Michael; Kapil, Vikas

2017-02-01

Over 40% of the world's population relies on solid fuels for heating and cooking. Use of improved biomass cookstoves (ICS) has the potential to reduce household air pollution (HAP). As part of an evaluation to identify ICS for use in Kenya, we collected indoor air and personal air samples to assess differences between traditional cookstoves (TCS) and ICS. We conducted a cross-over study in 2012 in two Kenyan villages; up to six different ICS were installed in 45 households during six two-week periods. Forty-eight hour kitchen measurements of fine particulate matter (PM 2.5 ) and carbon monoxide (CO) were collected for the TCS and ICS. Concurrent personal CO measurements were conducted on the mother and one child in each household. We performed descriptive analysis and compared paired measurements between baseline (TCS only) and each ICS. The geometric mean of 48-hour baseline PM 2.5 and CO concentrations in the kitchen was 586μg/m 3 (95% CI: 460, 747) and 4.9ppm (95% CI: 4.3, 5.5), respectively. For each ICS, the geometric mean kitchen air pollutant concentration was lower than the TCS: median reductions were 38.8% (95% CI: 29.5, 45.2) for PM 2.5 and 27.1% (95% CI: 17.4, 40.3) for CO, with statistically significant relationships for four ICS. We also observed a reduction in personal exposures to CO with ICS use. We observed a reduction in mean 48-hour PM 2.5 and CO concentrations compared to the TCS; however, concentrations for both pollutants were still consistently higher than WHO air quality guidelines. Our findings illustrate that ICS tested in real-world settings can reduce exposures to HAP, but implementation of cleaner fuels and related stove technologies may also be necessary to optimize public health benefits. Published by Elsevier Ltd.

Correlation Between Bladder Pain Syndrome/Interstitial Cystitis and Pelvic Inflammatory Disease

PubMed Central

Chung, Shiu-Dong; Chang, Chao-Hsiang; Hung, Peir-Haur; Chung, Chi-Jung; Muo, Chih-Hsin; Huang, Chao-Yuan

2015-01-01

Abstract Pelvic inflammatory disease (PID) has been investigated in Western countries and identified to be associated with chronic pelvic pain and inflammation. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a complex syndrome that is significantly more prevalent in women than in men. Chronic pelvic pain is a main symptom of BPS/IC, and chronic inflammation is a major etiology of BPS/IC. This study aimed to investigate the correlation between BPS/IC and PID using a population-based dataset. We constructed a case–control study from the Taiwan National Health Insurance program. The case cohort comprised 449 patients with BPS/IC, and 1796 randomly selected subjects (about 1:4 matching) were used as controls. A Multivariate logistic regression model was constructed to estimate the association between BPS/IC and PID. Of the 2245 sampled subjects, a significant difference was observed in the prevalence of PID between BPS/IC cases and controls (41.7% vs 15.4%, P < 0.001). Multivariate logistic regression analysis revealed that the odds ratio (OR) for PID among cases was 3.69 (95% confidence interval [CI]: 2.89–4.71). Furthermore, the ORs for PID among BPS/IC cases were 4.52 (95% CI: 2.55–8.01), 4.31 (95% CI: 2.91–6.38), 3.00 (95% CI: 1.82–4.94), and 5.35 (95% CI: 1.88–15.20) in the <35, 35–49, 50–64, and >65 years age groups, respectively, after adjusting for geographic region, irritable bowel syndrome, and hypertension. Joint effect was also noted, specifically when patients had both PID and irritable bowel disease with OR of 10.5 (95% CI: 4.88–22.50). This study demonstrated a correlation between PID and BPS/IC. Clinicians treating women with PID should be alert to BPS/IC-related symptoms in the population. PMID:26579800

Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

PubMed Central

Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

2013-01-01

A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations are provided. PMID:23620485

Cost-effectiveness analysis of smoking cessation interventions using cell phones in a low-income population.

PubMed

Daly, Allan T; Deshmukh, Ashish A; Vidrine, Damon J; Prokhorov, Alexander V; Frank, Summer G; Tahay, Patricia D; Houchen, Maggie E; Cantor, Scott B

2018-06-09

The prevalence of cigarette smoking is significantly higher among those living at or below the federal poverty level. Cell phone-based interventions among such populations have the potential to reduce smoking rates and be cost-effective. We performed a cost-effectiveness analysis of three smoking cessation interventions: Standard Care (SC) (brief advice to quit, nicotine replacement therapy and self-help written materials), Enhanced Care (EC) (SC plus cell phone-delivered messaging) and Intensive Care (IC) (EC plus cell phone-delivered counselling). Quit rates were obtained from Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods). We evaluated shorter-term outcomes of cost per quit and long-term outcomes using cost per quality-adjusted life year (QALY). For men, EC cost an additional $541 per quit vs SC; however, IC cost an additional $5232 per quit vs EC. For women, EC was weakly dominated by IC-IC cost an additional $1092 per quit vs SC. Similarly, for men, EC had incremental cost-effectiveness ratio (ICER) of $426 per QALY gained vs SC; however, IC resulted in ICER of $4127 per QALY gained vs EC. For women, EC was weakly dominated; the ICER of IC vs SC was $1251 per QALY gained. The ICER was below maximum acceptable willingness-to-pay threshold of $50 000 per QALY under all alternative modelling assumptions. Cell phone interventions for low socioeconomic groups are a cost-effective use of healthcare resources. Intensive Care was the most cost-effective strategy both for men and women. NCT00948129; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations

PubMed Central

Kashchenko, Nina I.; Chirikova, Nadezhda K.; Akobirshoeva, Anzurat; Zilfikarov, Ifrat N.; Vennos, Cecile

2017-01-01

Marigold (Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC50 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 36.47 µM), and the least active component was manghaslin (quercetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18–19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents. PMID:28767066

Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations.

PubMed

Olennikov, Daniil N; Kashchenko, Nina I; Chirikova, Nadezhda K; Akobirshoeva, Anzurat; Zilfikarov, Ifrat N; Vennos, Cecile

2017-08-02

Marigold ( Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC 50 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3- О -(2'',6''-di-acetyl)-glucoside (IC 50 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3- O -(2'',6''-di-rhamnosyl)-glucoside; IC 50 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3- О -(2'',6''-di-acetyl)-glucoside (IC 50 36.47 µM), and the least active component was manghaslin (quercetin-3- O -(2'',6''-di-rhamnosyl)-glucoside; IC 50 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18-19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents.

Fibromyalgia in 300 adult index patients with primary immunodeficiency.

PubMed

Barton, James C; Bertoli, Luigi F; Barton, Jackson C; Acton, Ronald T

2017-01-01

We sought to determine the prevalence and clinical and laboratory associations of fibromyalgia in adults with primary immunodeficiency (immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable immunodeficiency (CVID). We performed a retrospective analysis of these observations in 300 non-Hispanic white adult index patients with recurrent/severe respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia; chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC); diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed univariate comparisons, logistic multivariable regressions, and an analysis of covariance. Mean age was 49 ± 12 (standard deviation) y. There were 246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjögren's syndrome, 8.0%; IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in patients with fibromyalgia. Logistic regression on fibromyalgia revealed three positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence interval 1.2, 5.6]); Sjögren's syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC (p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant interactions of chronic fatigue, Sjögren's syndrome, and interstitial cystitis on fibromyalgia. Fibromyalgia is common in non-Hispanic white adult index patients with primary immunodeficiency, especially women. Chronic fatigue, Sjögren's syndrome, and IC are significantly associated with fibromyalgia after adjustment for other independent variables.

Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat.

PubMed

Masuda, Tadashi; Hida, Hideki; Kanda, Yoshie; Aihara, Noritaka; Ohta, Kengo; Yamada, Kazuo; Nishino, Hitoo

2007-01-01

Cerebral hemorrhage leads to local production of free iron, radicals, cytokines, etc. To investigate whether a decrease of iron-mediated radical production influences functional recovery after intracerebral hemorrhage (ICH), a modified ICH rat model with a small hemorrhage near the internal capsule (IC) accompanied with relatively severe motor dysfunction was first developed. Then clioquinol (CQ), an iron chelator that reduces hydroxyl radical production, was orally administrated. Injection of different doses of Type IV collagenase (1.4 mul 1-200 U/ml) into the left striatum near the IC in Wistar rats showed that injection of 7.5 U/ml collagenase resulted in a small hemorrhoidal lesion near the IC with relatively severe motor dysfunction (IC model). Retrograde labeling of neurons in the sensory-motor cortex and axons in the corticospinal tract using Fluoro-gold (FG) injection into the spinal cord (C3-C4) showed that few labeled neurons in the sensory-motor cortex were detected in the IC model, FG-labeled axons disappeared, and FG-including ED-1-positive cells appeared within 24 hr in the IC. Assessments of behavior and histologic analysis after oral administration of CQ in the IC model indicated that oral administration of CQ prevented a decrease of FG-labeled neurons, and resulted in better motor-function recovery. CQ inhibited hydrogen peroxide-induced cell toxicity in oligodendrocytes in vitro, but not in neurons. Our data suggests that CQ ameliorated motor dysfunction after a small hemorrhage near the IC by a mechanism that is related to reduction of chain-reactive hydroxyl radical production in oligodendrocytes.

Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel.

PubMed

Jensen, B S; Strobaek, D; Christophersen, P; Jorgensen, T D; Hansen, C; Silahtaroglu, A; Olesen, S P; Ahring, P K

1998-09-01

The human intermediate-conductance, Ca2+-activated K+ channel (hIK) was identified by searching the expressed sequence tag database. hIK was found to be identical to two recently cloned K+ channels, hSK4 and hIK1. RNA dot blot analysis showed a widespread tissue expression, with the highest levels in salivary gland, placenta, trachea, and lung. With use of fluorescent in situ hybridization and radiation hybrid mapping, hIK mapped to chromosome 19q13.2 in the same region as the disease Diamond-Blackfan anemia. Stable expression of hIK in HEK-293 cells revealed single Ca2+-activated K+ channels exhibiting weak inward rectification (30 and 11 pS at -100 and +100 mV, respectively). Whole cell recordings showed a noninactivating, inwardly rectifying K+ conductance. Ionic selectivity estimated from bi-ionic reversal potentials gave the permeability (PK/PX) sequence K+ = Rb+ (1.0) > Cs+ (10.4) > Na+, Li+, N-methyl-D-glucamine (>51). NH+4 blocked the channel completely. hIK was blocked by the classical inhibitors of the Gardos channel charybdotoxin (IC50 28 nM) and clotrimazole (IC50 153 nM) as well as by nitrendipine (IC50 27 nM), Stichodactyla toxin (IC50 291 nM), margatoxin (IC50 459 nM), miconazole (IC50 785 nM), econazole (IC50 2.4 microM), and cetiedil (IC50 79 microM). Finally, 1-ethyl-2-benzimidazolinone, an opener of the T84 cell IK channel, activated hIK with an EC50 of 74 microM.

Isolation and characterization of isochorismate synthase and cinnamate 4-hydroxylase during salinity stress, wounding, and salicylic acid treatment in Carthamus tinctorius

PubMed Central

Sadeghi, Mahnaz; Dehghan, Sara; Fischer, Rainer; Wenzel, Uwe; Vilcinskas, Andreas; Kavousi, Hamid Reza; Rahnamaeian, Mohammad

2013-01-01

Salicylic acid (SA) is a prominent signaling molecule during biotic and abiotic stresses in plants biosynthesized via cinnamate and isochorismate pathways. Cinnamate 4-hydroxylase (C4H) and isochorismate synthase (ICS) are the main enzymes in phenylpropanoid and isochorismate pathways, respectively. To investigate the actual roles of these genes in resistance mechanism to environmental stresses, here, the coding sequences of these enzymes in safflower (Carthamus tinctorius), as an oilseed industrial medicinal plant, were partially isolated and their expression profiles during salinity stress, wounding, and salicylic acid treatment were monitored. As a result, safflower ICS (CtICS) and C4H (CtC4H) were induced in early time points after wounding (3–6 h). Upon salinity stress, CtICS and CtC4H were highly expressed for the periods of 6–24 h and 3–6 h after treatment, respectively. It seems evident that ICS expression level is SA concentration dependent as if safflower treatment with 1 mM SA could induce ICS much stronger than that with 0.1 mM, while C4H is less likely to be so. Based on phylogenetic analysis, safflower ICS has maximum similarity to its ortholog in Vitis vinifera up to 69%, while C4H shows the highest similarity to its ortholog in Echinacea angustifolia up to 96%. Overall, the isolated genes of CtICS and CtC4H in safflower could be considered in plant breeding programs for salinity tolerance as well as for pathogen resistance. PMID:24309561

Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study.

PubMed

Villacorta, Aline Sterque; Villacorta, Humberto; Souza, Jenne Serrão de; Teixeira, José Antônio Caldas; Muradas, Maria Clara S S S; Alves, Christiane Rodrigues; Precht, Bernardo Campanário; Porto, Pilar; Ubaldo, Letícia; Mesquita, Cláudio Tinoco; Nóbrega, Antônio Cláudio Lucas da

2016-11-01

In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood. To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Mean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001). Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation. No SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial, ou Estudo do Tratamento da Insuficiência Cardíaca Sistólica com o Inibidor de If Ivabradina), a redução da frequência cardíaca (FC) com ivabradina associou-se com melhor sobrevida e redução das hospitalizações em pacientes com insuficiência cardíaca (IC). Os mecanismos pelos quais a FC elevada aumenta a mortalidade não são totalmente compreendidos. Avaliar a relação da FC basal com atividade clínica, neuro-hormonal e simpática cardíaca em pacientes com IC crônica e FC elevada. Pacientes com IC crônica em ritmo sinusal e FC≥70 apesar de tratamento adequado foram incluídos em um estudo duplo-cego, randomizado, que comparou ivabradina com piridostigmina. Este artigo refere-se a dados basais dos primeiros 16 pacientes. A FC basal (antes da randomização para um dos medicamentos) foi avaliada, e os pacientes classificados em dois grupos, com FC abaixo ou acima dos valores médios. A atividade simpática cardíaca foi avaliada por cintilografia com metaiodobenzilguanidina marcada com iodo 123. A FC média foi 83,5±11,5 bpm (intervalo 72 a 104), e sete pacientes (43.7%) tinham FC acima da média. Esses pacientes apresentaram menor distância percorrida no teste de caminhada de 6 minutos (292,3±93 vs 465,2±97,1 m, p=0,0029), valores mais altos de N-terminal do pró-BNP (mediana 708,4 vs 76,1, p=0,035) e menor relação coração/mediastino tardia, indicando desnervação cardíaca (1,48±0,12 vs 1,74±0,09, p<0,001). A FC de repouso elevada em pacientes com IC em tratamento médico adequado associou-se com desnervação cardíaca, pior capacidade funcional e ativação neuro-hormonal.

Health-related Quality of Life of Patients With Chronic Systolic Heart Failure in Spain: Results of the VIDA-IC Study.

PubMed

Comín-Colet, Josep; Anguita, Manuel; Formiga, Francesc; Almenar, Luis; Crespo-Leiro, María G; Manzano, Luis; Muñiz, Javier; Chaves, José; de Frutos, Trinidad; Enjuanes, Cristina

2016-03-01

Although heart failure negatively affects the health-related quality of life of Spanish patients there is little information on the clinical factors associated with this issue. Cross-sectional multicenter study of health-related quality of life. A specific questionnaire (Kansas City Cardiomyopathy Questionnaire) and a generic questionnaire (EuroQoL-5D) were administered to 1037 consecutive outpatients with systolic heart failure. Most patients with poor quality of life had a worse prognosis and increased severity of heart failure. Mobility was more limited and rates of pain/discomfort and anxiety/depression were higher in the study patients than in the general population and patients with other chronic conditions. The scores on both questionnaires were very highly correlated (Pearson r =0.815; P < .001). Multivariable linear regression showed that being older (standardized β=-0.2; P=.03), female (standardized β=-10.3; P < .001), having worse functional class (standardized β=-20.4; P < .001), a higher Charlson comorbidity index (standardized β=-1.2; P=.005), and recent hospitalization for heart failure (standardized β=6.28; P=.006) were independent predictors of worse health-related quality of life. Patients with heart failure have worse quality of life than the general Spanish population and patients with other chronic diseases. Female sex, being older, comorbidity, advanced symptoms, and recent hospitalization are determinant factors in health-related quality of life in these patients. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Long-term reproducibility of relative sensitivity factors obtained with CAMECA Wf

NASA Astrophysics Data System (ADS)

Gui, D.; Xing, Z. X.; Huang, Y. H.; Mo, Z. Q.; Hua, Y. N.; Zhao, S. P.; Cha, L. Z.

2008-12-01

As the wafer size continues to increase and the feature size of the integrated circuits (IC) continues to shrink, process control of IC manufacturing becomes ever more important to reduce the cost of failures caused by the drift of processes or equipments. Characterization tools with high precision and reproducibility are required to capture any abnormality of the process. Although Secondary ion mass spectrometry (SIMS) has been widely used in dopant profile control, it was reported that magnetic sector SIMS, compared to quadrupole SIMS, has lower short-term repeatability and long-term reproducibility due to the high extraction field applied between sample and extraction lens. In this paper, we demonstrate that CAMECA Wf can deliver high long-term reproducibility because of its high-level automation and improved design of immersion lens. The relative standard deviation (R.S.D.) of the relative sensitivity factors (RSF) of three typical elements, i.e., boron (B), phosphorous (P) and nitrogen (N), over 3 years are 3.7%, 5.5% and 4.1%, respectively. The high reproducibility results have a practical implication that deviation can be estimated without testing the standards.

Microwave evaluation of electromigration susceptibility in advanced interconnects

NASA Astrophysics Data System (ADS)

Sunday, Christopher E.; Veksler, Dmitry; Cheung, Kin C.; Obeng, Yaw S.

2017-11-01

Traditional metrology has been unable to adequately address the needs of the emerging integrated circuits (ICs) at the nano scale; thus, new metrology and techniques are needed. For example, the reliability challenges in fabrication need to be well understood and controlled to facilitate mass production of through-substrate-via (TSV) enabled three-dimensional integrated circuits (3D-ICs). This requires new approaches to the metrology. In this paper, we use the microwave propagation characteristics to study the reliability issues that precede the physical damage caused by electromigration in the Cu-filled TSVs. The pre-failure microwave insertion losses and group delay are dependent on both the device temperature and the amount of current forced through the devices-under-test. The microwave insertion losses increase with the increase in the test temperature, while the group delay increases with the increase in the forced direct current magnitude. The microwave insertion losses are attributed to the defect mobility at the Cu-TiN interface, and the group delay changes are due to resistive heating in the interconnects, which perturbs the dielectric properties of the cladding dielectrics of the copper fill in the TSVs.

[Percutaneous nephrolithotomy for kidney stones in elderly patients: Meta-analysis of results and complications].

PubMed

Haider, R; Regnier, P; Roustan, F-R; Séverac, F; Treacy, P-J; Mendel, L; Bodokh, Y; Tibi, B; Prader, R; Traxer, O; Chevallier, D; Amiel, J; Durand, M

2017-02-01

Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for kidney stones regardless of age. Elderly patients (EP)≥65years old, in growing numbers, have more comorbidities than the general population, may alter results of PCNL. The aim of this meta-analysis was to compare efficacy and complications of this procedure between EP and young patients (YP). Original studies of prospective and historical cohorts, in English or French, presenting PCNL series published on PubMed until 2015 were identified using the keywords percutaneous nephrolithotomy, elderly patients, kidney stones and staghorn calculi. Our analysis focused on therapeutic efficacy, defined by absence of residual fragment or the presence of residual fragments<4mm at 3 postoperative months, and postoperative complications according to patient age: YP<65 years old and EP≥65 years old. Binary qualitative data were analyzed using odds ratio (OR) and quantitative data by estimating the difference of means. In total 397 studies were identified among which 23 were checked and 8 included in the meta-analysis for methodological quality corresponding to 4995 YP and 820 EP. No efficacy difference (OR=0.96; [IC95 %: 0.80; 1.17]; P=0.71), operating time (+1.15min in EP [IC95 %: -2.83; 5.12]; P=0.57) and average length of stay (+0.29 days in EP [IC95 %: -0.14; 0.72]; P=0.19) has been reported. It was a trend to more urinary infections (OR=2.24; [IC95 %: 0.74-6.80]; P=0.16) and a significantly increase of postoperative blood transfusions in EP (OR=1.41; [IC95 %: 1.00-1.97]; P=0.04). PCNL for kidney stones n EP is effective with a significantly increase the risk of postoperative blood transfusions compared to YP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Do Different ADHD-Related Etiological Risks Involve Specific Neuropsychological Pathways? An Analysis of Mediation Processes by Inhibitory Control and Delay Aversion

ERIC Educational Resources Information Center

Pauli-Pott, Ursula; Dalir, Silke; Mingebach, Tanja; Roller, Alisa; Becker, Katja

2013-01-01

Background: Inhibitory control (IC) has been regarded as a neuropsychological basic deficit and as an endophenotype of attention deficit/hyperactivity disorder (ADHD). Implicated here are mediation processes between etiological factors and ADHD symptoms. We thus analyze whether and to what extent executive IC and delay aversion (DA; i.e.,…

Assessment of hair cortisol as a potential biomarker for possible adrenal suppression due to inhaled corticosteroid use in children with asthma: A retrospective observational study.

PubMed

Smy, Laura; Shaw, Kaitlyn; Amstutz, Ursula; Staub, Michelle; Chaudhry, Shahnaz; Smith, Anne; Carleton, Bruce; Koren, Gideon

2018-06-01

Inhaled corticosteroids (ICS) are the recommended long-term control therapy for asthma in children. However, concern exists regarding potential adrenal suppression with chronic ICS use. Our pilot study reported that hair cortisol in children was 50% lower during ICS therapy than prior to therapy, suggestive of adrenal suppression. To evaluate hair cortisol concentration (HCC) as a potential biomarker for possible adrenal suppression from ICS use in children with asthma. A retrospective observational study was performed at asthma clinics in Vancouver, Winnipeg, and Toronto, Canada. Children (n = 586) were recruited from July 2012 to December 2014 inclusive of those without asthma, with asthma not using ICS, and with asthma using ICS. The most recent three-month HCC was measured by enzyme immunoassay and compared among the groups. Quantile regression analysis was performed to identify factors potentially affecting HCC. The median HCC was not significantly different among the children: No ICS (n = 47, 6.7 ng/g, interquartile range (IQR) 3.7-9.8 ng/g), ICS Treated (n = 360, 6.5 ng/g, IQR 3.8-14.3 ng/g), and Controls (n = 53, 5.8 ng/g, IQR 4.6-16.7 ng/g). 5.6% of the children using ICS had hair cortisol <2.0 ng/g compared to none in the control groups (P < .05, comparing ICS Treated (20/360) to all Controls combined (0/100)) and only half had been exposed to systemic corticosteroids. Age, sex, BMI, and intranasal corticosteroid use were significantly associated with HCC. Results suggest HCC may be a potential biomarker for adrenal suppression as a population of children using ICS with HCC < 2.0 ng/g was identified compared to none in the control groups. Further research is needed to determine if those children have or are at risk of adrenal suppression or insufficiency. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Simulation of materials processing: Fantasy or reality?

NASA Technical Reports Server (NTRS)

Jenkins, Thomas J.; Bright, Victor M.

1994-01-01

This experiment introduces students to the application of computer-aided design (CAD) and analysis of materials processing in the context of integrated circuit (IC) fabrication. The fabrication of modern IC's is a complex process which consists of several sequential steps. These steps involve the precise control of processing variables such as temperature, humidity, and ambient gas composition. In essence, the particular process employed during the fabrication becomes a 'recipe'. Due to economic and other considerations, CAD is becoming an indispensable part of the development of new recipes for IC fabrication. In particular, this experiment permits the students to explore the CAD of the thermal oxidation of silicon.

Health economic impact of high-dose versus standard-dose cytarabine induction chemotherapy for acute myeloid leukaemia.

PubMed

Fedele, P L; Avery, S; Patil, S; Spencer, A; Haas, M; Wei, A

2014-08-01

Induction chemotherapy for acute myeloid leukaemia (AML) is one of the most resource-intensive cancer therapies delivered in hospitals. To assess the health resource impact of different chemotherapy approaches for AML commonly used in Australia. A retrospective analysis was undertaken in 63 patients aged 18-55 years with AML given induction with either 7 + 3 (cytarabine 100 mg/m(2) days 1-7 and idarubicin 12 mg/m(2) days 1-3) or HiDAC-3 (high-dose cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7 and idarubicin 12 mg/m(2) days 1-3) chemotherapy. Average costs of hospitalisation, pathology, radiology, chemotherapy and ancillary drugs were calculated and compared with current Victorian casemix funding. Two consolidation approaches, HiDAC (cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7) × either three or four cycles (following 7 + 3) and IcE (idarubicin 12,mg/m(2) days 1-2, cytarabine 100 mg/m(2) × 5 days and etoposide 75 mg/m(2) × 5 days) × 2 cycles (following HiDAC-3) were modelled, using a policy of discharge following completion of chemotherapy with outpatient monitoring. The cost (in AUD) of induction was similar between 7 + 3 ($58,037) and HiDAC-3 ($56,902), with bed day costs accounting for 61-62% of the total expense. Blood bank costs ranked second, accounting for 15%. Accumulated costs for HiDAC consolidation were $44,289 for a three-cycle protocol and $59,052 for four cycles ($14,763 per cycle) versus $31,456 for two cycles of IcE consolidation ($15,728 per cycle). Overall, the classical 7 + 3 → HiDAC approach ($102,326/$117,089 for three or four consolidation cycles) incurs a greater cost than a HiDAC-3 → IcE × 2 approach ($88,358). For patients requiring complete hospitalisation until neutrophil recovery, the estimated costs of treatment will be even higher, ranging between $122,282 for HiDAC-3 → IcE × 2, $153,212 for 7 + 3 → HiDAC × 3 and $184,937 for 7 + 3 → HiDAC × 4. State-based casemix funding for non-complicated AML therapy is currently $74,013 for 7 + 3 → HiDAC × 4, $64,177 for 7 + 3 → HiDAC × 3 and $54,340 for HiDAC-3 → IcE × 2 based on outpatient recovery after consolidation chemotherapy. These calculations do not take into account additional resource implications associated with complications of consolidation chemotherapy or reinduction for treatment failure. Regimens minimising the total number of chemotherapy cycles may represent the most efficient use of limited health resources for the treatment of AML. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Development of a Highly Specific Fluorescence Immunoassay for Detection of Diisobutyl Phthalate in Edible Oil Samples.

PubMed

Cui, Xiping; Wu, Panpan; Lai, Dan; Zheng, Shengwu; Chen, Yingshan; Eremin, Sergei A; Peng, Wei; Zhao, Suqing

2015-10-28

The diisobutyl phthalate (DiBP) hapten containing an amino group was synthesized successfully, and the polyclonal antibody against 4-amino phthalate-bovine serum albumin (BSA) was developed. On the basis of the polyclonal antibody, a rapid and sensitive indirect competitive fluorescence immunoassay (icFIA) has been established to detect DiBP in edible oil samples for the first time. Under the optimized conditions, the quantitative working range of the icFIA was from 10.47 to 357.06 ng/mL (R(2) = 0.991), exhibiting a detection limit of 5.82 ng/mL. In this assay, the specific results showed that other similar phthalates did not significantly interfere with the analysis, with the cross-reactivity less than 1.5%, except for that of DiBAP. Thereafter, DiBP contamination in edible oil samples was detected by icFIA, with the recovery being from 79 to 103%. Furthermore, the reliability of icFIA was validated by gas chromatography-mass spectrometry (GC-MS). Therefore, the developed icFIA is suitable for monitoring DiBP in some edible oil samples.

In situ high-resolution thermal microscopy on integrated circuits.

PubMed

Zhuo, Guan-Yu; Su, Hai-Ching; Wang, Hsien-Yi; Chan, Ming-Che

2017-09-04

The miniaturization of metal tracks in integrated circuits (ICs) can cause abnormal heat dissipation, resulting in electrostatic discharge, overvoltage breakdown, and other unwanted issues. Unfortunately, locating areas of abnormal heat dissipation is limited either by the spatial resolution or imaging acquisition speed of current thermal analytical techniques. A rapid, non-contact approach to the thermal imaging of ICs with sub-μm resolution could help to alleviate this issue. In this work, based on the intensity of the temperature-dependent two-photon fluorescence (TPF) of Rhodamine 6G (R6G) material, we developed a novel fast and non-invasive thermal microscopy with a sub-μm resolution. Its application to the location of hotspots that may evolve into thermally induced defects in ICs was also demonstrated. To the best of our knowledge, this is the first study to present high-resolution 2D thermal microscopic images of ICs, showing the generation, propagation, and distribution of heat during its operation. According to the demonstrated results, this scheme has considerable potential for future in situ hotspot analysis during the optimization stage of IC development.

Posterior insular cortex – a site of vestibular–somatosensory interaction?

PubMed Central

Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-01-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

Iterative categorization (IC): a systematic technique for analysing qualitative data.

PubMed

Neale, Joanne

2016-06-01

The processes of analysing qualitative data, particularly the stage between coding and publication, are often vague and/or poorly explained within addiction science and research more broadly. A simple but rigorous and transparent technique for analysing qualitative textual data, developed within the field of addiction, is described. The technique, iterative categorization (IC), is suitable for use with inductive and deductive codes and can support a range of common analytical approaches, e.g. thematic analysis, Framework, constant comparison, analytical induction, content analysis, conversational analysis, discourse analysis, interpretative phenomenological analysis and narrative analysis. Once the data have been coded, the only software required is a standard word processing package. Worked examples are provided. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.

PubMed

Rosenberg, Jonathan E; Hoffman-Censits, Jean; Powles, Tom; van der Heijden, Michiel S; Balar, Arjun V; Necchi, Andrea; Dawson, Nancy; O'Donnell, Peter H; Balmanoukian, Ani; Loriot, Yohann; Srinivas, Sandy; Retz, Margitta M; Grivas, Petros; Joseph, Richard W; Galsky, Matthew D; Fleming, Mark T; Petrylak, Daniel P; Perez-Gracia, Jose Luis; Burris, Howard A; Castellano, Daniel; Canil, Christina; Bellmunt, Joaquim; Bajorin, Dean; Nickles, Dorothee; Bourgon, Richard; Frampton, Garrett M; Cui, Na; Mariathasan, Sanjeev; Abidoye, Oyewale; Fine, Gregg D; Dreicer, Robert

2016-05-07

Patients with metastatic urothelial carcinoma have few treatment options after failure of platinum-based chemotherapy. In this trial, we assessed treatment with atezolizumab, an engineered humanised immunoglobulin G1 monoclonal antibody that binds selectively to programmed death ligand 1 (PD-L1), in this patient population. For this multicentre, single-arm, two-cohort, phase 2 trial, patients (aged ≥18 years) with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy were enrolled from 70 major academic medical centres and community oncology practices in Europe and North America. Key inclusion criteria for enrolment were Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), adequate haematological and end-organ function, and no autoimmune disease or active infections. Formalin-fixed paraffin-embedded tumour specimens with sufficient viable tumour content were needed from all patients before enrolment. Patients received treatment with intravenous atezolizumab (1200 mg, given every 3 weeks). PD-L1 expression on tumour-infiltrating immune cells (ICs) was assessed prospectively by immunohistochemistry. The co-primary endpoints were the independent review facility-assessed objective response rate according to RECIST v1.1 and the investigator-assessed objective response rate according to immune-modified RECIST, analysed by intention to treat. A hierarchical testing procedure was used to assess whether the objective response rate was significantly higher than the historical control rate of 10% at an α level of 0·05. This study is registered with ClinicalTrials.gov, number NCT02108652. Between May 13, 2014, and Nov 19, 2014, 486 patients were screened and 315 patients were enrolled into the study. Of these patients, 310 received atezolizumab treatment (five enrolled patients later did not meet eligibility criteria and were not dosed with study drug). The PD-L1 expression status on infiltrating immune cells (ICs) in the tumour microenvironment was defined by the percentage of PD-L1-positive immune cells: IC0 (<1%), IC1 (≥1% but <5%), and IC2/3 (≥5%). The primary analysis (data cutoff May 5, 2015) showed that compared with a historical control overall response rate of 10%, treatment with atezolizumab resulted in a significantly improved RECIST v1.1 objective response rate for each prespecified immune cell group (IC2/3: 27% [95% CI 19-37], p<0·0001; IC1/2/3: 18% [13-24], p=0·0004) and in all patients (15% [11-20], p=0·0058). With longer follow-up (data cutoff Sept 14, 2015), by independent review, objective response rates were 26% (95% CI 18-36) in the IC2/3 group, 18% (13-24) in the IC1/2/3 group, and 15% (11-19) overall in all 310 patients. With a median follow-up of 11·7 months (95% CI 11·4-12·2), ongoing responses were recorded in 38 (84%) of 45 responders. Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolizumab. Grade 3-4 treatment-related adverse events, of which fatigue was the most common (five patients [2%]), occurred in 50 (16%) of 310 treated patients. Grade 3-4 immune-mediated adverse events occurred in 15 (5%) of 310 treated patients, with pneumonitis, increased aspartate aminotransferase, increased alanine aminotransferase, rash, and dyspnoea being the most common. No treatment-related deaths occurred during the study. Atezolizumab showed durable activity and good tolerability in this patient population. Increased levels of PD-L1 expression on immune cells were associated with increased response. This report is the first to show the association of TCGA subtypes with response to immune checkpoint inhibition and to show the importance of mutation load as a biomarker of response to this class of agents in advanced urothelial carcinoma. F Hoffmann-La Roche Ltd. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative Study of Erythrina indica Lam. (Febaceae) Leaves Extracts for Antioxidant Activity

PubMed Central

Sakat, SS; Juvekar, AR

2010-01-01

The present study was designed to investigate the antioxidant activity of aqueous and methanol extracts of Erythrina indica Lam leaves by in vitro methods viz. 1, 1-Diphenyl-2-Picrylhydrazyl, nitric oxide radical scavenging activity, and inhibition of lipid peroxidation by thiobarbituric acid reactive substances (TBARS) method on isolated rat liver tissues. Quantitative analysis of antioxidative components like total amount of phenolics, flavonoids, and flavonols were estimated using the spectrophotometric method. Linear regression analysis was used to calculate the IC50 value. Results showed that the aqueous and methanol extracts exhibited significant DPPH radicals scavenging activity with an IC50 value 342.59 ± 19.59, 283.24 ± 12.28 µg/mL respectively. Nitric oxide radicals were significantly scavenged by the aqueous and methanol extracts (IC50 = 250.12 ± 10.66; 328.29 ± 3.74 µg/mL). Lipid peroxidation induced by the Fe2+ was inhibited by the aqueous extract with low IC50 value (97.29 ± 2.05 µg/mL) as compared to methanol extract (IC50 = 283.74 ± 5.70 µg/mL). Both the extracts were exhibited similar quantities of total phenolics. Total flavonoids were found to be in higher quantities than total flavonols in aqueous extract as compared to methanol extract. From the results, it is concluded that the aqueous and methanol extracts of E. indica leaves possesses significant antioxidant activity that may be due to the presence of flavonoids and related polyphenolic compounds. PMID:21331194

Energy and women's economic empowerment: Rethinking the benefits of improved cookstove use in rural India

NASA Astrophysics Data System (ADS)

Seaward, James Nicholas

International development organizations have recently ramped up efforts to promote the use of improved cookstoves (ICS) in developing countries, aiming to reduce the harmful environmental and public health impacts of the burning of biomass for cooking and heating. I hypothesize that ICS use also has additional benefits---economic and social benefits---that can contribute to women's economic empowerment in the developing world. To explore the relationship between ICS use and women's economic empowerment, I use Ordinary Least Squares and Logit models based on data from the India Human Development Survey (IHDS) to analyze differences between women living in households that use ICS and those living in homes that use traditional cookstoves. My regression results reveal that ICS use has a statistically significant and negative effect on the amount of time women and girls spend on fuel collection and a statistically significant and positive effect on the likelihood of women's participation in side businesses, but does not have a statistically significant effect on the likelihood of lost productivity. My analysis shows promise that in addition to health and environmental benefits, fuel-efficient cooking technologies can also have social and economic impacts that are especially beneficial to women. It is my hope that the analysis provided in this paper will be used to further the dialogue about the importance of women's access to modern energy services in the fight to improve women's living standards in the developing world.

Organic solvent and temperature-enhanced ion chromatography-high resolution mass spectrometry for the determination of low molecular weight organic and inorganic anions.

PubMed

Gilchrist, Elizabeth S; Nesterenko, Pavel N; Smith, Norman W; Barron, Leon P

2015-03-20

There has recently been increased interest in coupling ion chromatography (IC) to high resolution mass spectrometry (HRMS) to enable highly sensitive and selective analysis. Herein, the first comprehensive study focusing on the direct coupling of suppressed IC to HRMS without the need for post-suppressor organic solvent modification is presented. Chromatographic selectivity and added HRMS sensitivity offered by organic solvent-modified IC eluents on a modern hyper-crosslinked polymeric anion-exchange resin (IonPac AS18) are shown using isocratic eluents containing 5-50 mM hydroxide with 0-80% methanol or acetonitrile for a range of low molecular weight anions (<165 Da). Comprehensive experiments on IC thermodynamics over a temperature range between 20-45 °C with the eluent containing up to 60% of acetonitrile or methanol revealed markedly different retention behaviour and selectivity for the selected analytes on the same polymer based ion-exchange resin. Optimised sensitivity with HRMS was achieved with as low as 30-40% organic eluent content. Analytical performance characteristics are presented and compared with other IC-MS based works. This study also presents the first application of IC-HRMS to forensic detection of trace low-order anionic explosive residues in latent human fingermarks. Copyright © 2015 Elsevier B.V. All rights reserved.

Postimplant left ventricular assist device fit analysis using three-dimensional reconstruction.

PubMed

Truong, Thang V; Stanfield, J Ryan; Chaffin, John S; Elkins, C Craig; Kanaly, Paul J; Horstmanshof, Douglas A; Long, James W; Snyder, Trevor A

2013-01-01

Left ventricular assist devices (LVADs) are blood pumps that augment the function of the failing heart to improve perfusion, resulting in improved survival. For LVADs to effectively unload the left ventricle, the inflow cannula (IC) should be unobstructed and ideally aligned with the heart's mitral valve (MV). We examined IC orientation deviation from a hypothesized conventional angle (45° right-posterior) and the approximate angle for direct IC-MV alignment in many patients. Three-dimensional anatomic models were created from computed tomography scans for 24 LVAD-implanted patients, and angles were measured between the IC and the apical z-axis in both the coronal and the sagittal planes. Common surgical IC angulation was found to be 22 ± 15° rightward and 21 ± 12° posterior from the apical z-axis; 38% (n = 9) of patients fell in this range. Direct IC-MV angulation was found to be 34 ± 8° rightward and 15 ± 7° posterior; only 8% (n = 2) of patients fell in this range. Rightward deviation toward ventricular septal wall and anterior deviation toward LV anterior freewall are associated with mortalities more so than leftward and posterior deviation. In conclusion, anatomic reconstruction may be a useful preoperative tool to obtain general population and patient-specific alignment for optimal LVAD implantation.

The Chiasmus of Design: Paradoxical Outcomes in the e-Government Reform of UK Children's Services

NASA Astrophysics Data System (ADS)

Wastell, David; White, Sue; Broadhurst, Karen

This paper describes a detailed ethnographic study of the design problems of a major national IT system in the UK- The Integrated Children’s System (ICS). The implementation of the ICS has disrupted social work practice and engendered growing professional resistance, prompting a fundamental review of its design. Marshall McLuhan’s concept of chiasmus is a central feature of our analysis of the vicissitudes of ICS. Chiasmus refers to the tendency of any system, when pushed too far, to produce unintended contradictory effects, and is an intrinsic feature of the behaviour of complex, socio-technical systems. The dysfunctions of the ICS provide a pertinent, large-scale example. The ICS constitutes an attempt, via technological means, to re-organize child welfare services in the UK. Whilst aimed at improving child safety, the ICS has had the opposite effect of increasing the potential for error. This chiasmus has been exposed through the multi-site ethnography reported here, which shows how rigidly designed processes, enforced by IT systems, force social work professionals into unsafe investigative and recording practices which increase the risk of errors. The paper ends by proposing an alternative approach to design, based on socio-technical precepts, emphasizing the principles of minimum critical specification, user-centeredness and local autonomy.

Interpolation bias for the inverse compositional Gauss-Newton algorithm in digital image correlation

NASA Astrophysics Data System (ADS)

Su, Yong; Zhang, Qingchuan; Xu, Xiaohai; Gao, Zeren; Wu, Shangquan

2018-01-01

It is believed that the classic forward additive Newton-Raphson (FA-NR) algorithm and the recently introduced inverse compositional Gauss-Newton (IC-GN) algorithm give rise to roughly equal interpolation bias. Questioning the correctness of this statement, this paper presents a thorough analysis of interpolation bias for the IC-GN algorithm. A theoretical model is built to analytically characterize the dependence of interpolation bias upon speckle image, target image interpolation, and reference image gradient estimation. The interpolation biases of the FA-NR algorithm and the IC-GN algorithm can be significantly different, whose relative difference can exceed 80%. For the IC-GN algorithm, the gradient estimator can strongly affect the interpolation bias; the relative difference can reach 178%. Since the mean bias errors are insensitive to image noise, the theoretical model proposed remains valid in the presence of noise. To provide more implementation details, source codes are uploaded as a supplement.

Inhaled corticosteroids in chronic obstructive pulmonary disease: a pro–con perspective

PubMed Central

Babu, K Suresh; Kastelik, Jack A; Morjaria, Jaymin B

2014-01-01

Current guidelines limit regular use of inhaled corticosteroids (ICS) to a specific subgroup of patients with chronic obstructive pulmonary disease (COPD) in whom the forced expiratory volume in 1 s is <60% of predicted and who have frequent exacerbations. In these patients, there is evidence that ICS reduce the frequency of exacerbations and improve lung function and quality of life. However, a review of the literature suggests that the evidence available may be interpreted to favour or contradict these observations. It becomes apparent that COPD is a heterogeneous condition. Clinicians therefore need to be aware of the heterogeneity as well as having an understanding of how ICS may be used in the context of the specific subgroups of patients with COPD. This review argues for and against the use of ICS in COPD by providing an in-depth analysis of the currently available evidence. PMID:25099256

Why Flash Type Matters: A Statistical Analysis

NASA Astrophysics Data System (ADS)

Mecikalski, Retha M.; Bitzer, Phillip M.; Carey, Lawrence D.

2017-09-01

While the majority of research only differentiates between intracloud (IC) and cloud-to-ground (CG) flashes, there exists a third flash type, known as hybrid flashes. These flashes have extensive IC components as well as return strokes to ground but are misclassified as CG flashes in current flash type analyses due to the presence of a return stroke. In an effort to show that IC, CG, and hybrid flashes should be separately classified, the two-sample Kolmogorov-Smirnov (KS) test was applied to the flash sizes, flash initiation, and flash propagation altitudes for each of the three flash types. The KS test statistically showed that IC, CG, and hybrid flashes do not have the same parent distributions and thus should be separately classified. Separate classification of hybrid flashes will lead to improved lightning-related research, because unambiguously classified hybrid flashes occur on the same order of magnitude as CG flashes for multicellular storms.

The intelligibility in Context Scale: validity and reliability of a subjective rating measure.

PubMed

McLeod, Sharynne; Harrison, Linda J; McCormack, Jane

2012-04-01

To describe a new measure of functional intelligibility, the Intelligibility in Context Scale (ICS), and evaluate its validity, reliability, and sensitivity using 3 clinical measures of severity of speech sound disorder: (a) percentage of phonemes correct (PPC), (b) percentage of consonants correct (PCC), and (c) percentage of vowels correct (PVC). Speech skills of 120 preschool children (109 with parent-/teacher-identified concern about how they talked and made speech sounds and 11 with no identified concern) were assessed with the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Parents completed the 7-item ICS, which rates the degree to which children's speech is understood by different communication partners (parents, immediate family, extended family, friends, acquaintances, teachers, and strangers) on a 5-point scale. Parents' ratings showed that most children were always (5) or usually (4) understood by parents, immediate family, and teachers, but only sometimes (3) by strangers. Factor analysis confirmed the internal consistency of the ICS items; therefore, ratings were averaged to form an overall intelligibility score. The ICS had high internal reliability (α = .93), sensitivity, and construct validity. Criterion validity was established through significant correlations between the ICS and PPC (r = .54), PCC (r = .54), and PVC (r = .36). The ICS is a promising new measure of functional intelligibility. These data provide initial support for the ICS as an easily administered, valid, and reliable estimate of preschool children's intelligibility when speaking with people of varying levels of familiarity and authority.

Systematic assessment of survey scan and MS2-based abundance strategies for label-free quantitative proteomics using high-resolution MS data.

PubMed

Tu, Chengjian; Li, Jun; Sheng, Quanhu; Zhang, Ming; Qu, Jun

2014-04-04

Survey-scan-based label-free method have shown no compelling benefit over fragment ion (MS2)-based approaches when low-resolution mass spectrometry (MS) was used, the growing prevalence of high-resolution analyzers may have changed the game. This necessitates an updated, comparative investigation of these approaches for data acquired by high-resolution MS. Here, we compared survey scan-based (ion current, IC) and MS2-based abundance features including spectral-count (SpC) and MS2 total-ion-current (MS2-TIC), for quantitative analysis using various high-resolution LC/MS data sets. Key discoveries include: (i) study with seven different biological data sets revealed only IC achieved high reproducibility for lower-abundance proteins; (ii) evaluation with 5-replicate analyses of a yeast sample showed IC provided much higher quantitative precision and lower missing data; (iii) IC, SpC, and MS2-TIC all showed good quantitative linearity (R(2) > 0.99) over a >1000-fold concentration range; (iv) both MS2-TIC and IC showed good linear response to various protein loading amounts but not SpC; (v) quantification using a well-characterized CPTAC data set showed that IC exhibited markedly higher quantitative accuracy, higher sensitivity, and lower false-positives/false-negatives than both SpC and MS2-TIC. Therefore, IC achieved an overall superior performance than the MS2-based strategies in terms of reproducibility, missing data, quantitative dynamic range, quantitative accuracy, and biomarker discovery.

Systematic Assessment of Survey Scan and MS2-Based Abundance Strategies for Label-Free Quantitative Proteomics Using High-Resolution MS Data

PubMed Central

2015-01-01

Survey-scan-based label-free method have shown no compelling benefit over fragment ion (MS2)-based approaches when low-resolution mass spectrometry (MS) was used, the growing prevalence of high-resolution analyzers may have changed the game. This necessitates an updated, comparative investigation of these approaches for data acquired by high-resolution MS. Here, we compared survey scan-based (ion current, IC) and MS2-based abundance features including spectral-count (SpC) and MS2 total-ion-current (MS2-TIC), for quantitative analysis using various high-resolution LC/MS data sets. Key discoveries include: (i) study with seven different biological data sets revealed only IC achieved high reproducibility for lower-abundance proteins; (ii) evaluation with 5-replicate analyses of a yeast sample showed IC provided much higher quantitative precision and lower missing data; (iii) IC, SpC, and MS2-TIC all showed good quantitative linearity (R2 > 0.99) over a >1000-fold concentration range; (iv) both MS2-TIC and IC showed good linear response to various protein loading amounts but not SpC; (v) quantification using a well-characterized CPTAC data set showed that IC exhibited markedly higher quantitative accuracy, higher sensitivity, and lower false-positives/false-negatives than both SpC and MS2-TIC. Therefore, IC achieved an overall superior performance than the MS2-based strategies in terms of reproducibility, missing data, quantitative dynamic range, quantitative accuracy, and biomarker discovery. PMID:24635752

Exploring physical and chemical factors influencing the properties of recombinant prion protein and the real-time quaking-induced conversion (RT-QuIC) assay.

PubMed

Cheng, Keding; Sloan, Angela; Avery, Kristen M; Coulthart, Michael; Carpenter, Michael; Knox, J David

2014-01-01

Real-time quaking-induced conversion (RT-QuIC), a highly specific and sensitive assay able to detect low levels of the disease-inducing isoform of the prion protein (PrP(d)) in brain tissue biopsies and cerebral spinal fluid, has great potential to become a method for diagnosing prion disease ante mortem. In order to standardize the assay method for routine analysis, an understanding of how physical and chemical factors affect the stability of the recombinant prion protein (rPrP) substrate and the RT-QuIC assay's sensitivity, specificity, and reproducibility is required. In this study, using sporadic Creutzfeldt-Jakob Disease brain homogenate to seed the reactions and an in vitro-expressed recombinant prion protein, hamster rPrP, as the substrate, the following factors affecting the RT-QuIC assay were examined: salt and substrate concentrations, substrate storage, and pH. Results demonstrated that both the generation of the quality and quantities of rPrP substrate critical to the reaction, as well as the RT-QuIC reaction itself required strict adherence to specific physical and chemical conditions. Once optimized, the RT-QuIC assay was confirmed to be a very specific and sensitive assay method for sCJD detection. Findings in this study indicate that further optimization and standardization of RT-QuIC assay is required before it can be adopted as a routine diagnostic test.

Expression of a Diverse Array of Ca2+-Activated K+ Channels (SK1/3, IK1, BK) that Functionally Couple to the Mechanosensitive TRPV4 Channel in the Collecting Duct System of Kidney.

PubMed

Li, Yue; Hu, Hongxiang; Butterworth, Michael B; Tian, Jin-Bin; Zhu, Michael X; O'Neil, Roger G

2016-01-01

The voltage- and Ca2+-activated, large conductance K+ channel (BK, maxi-K) is expressed in the collecting duct system of kidney where it underlies flow- and Ca2+-dependent K+ excretion. To determine if other Ca2+-activated K+ channels (KCa) may participate in this process, mouse kidney and the K+-secreting mouse cortical collecting duct (CCD) cell line, mCCDcl1, were assessed for TRPV4 and KCa channel expression and cross-talk. qPCR mRNA analysis and immunocytochemical staining demonstrated TRPV4 and KCa expression in mCCDcl1 cells and kidney connecting tubule (CNT) and CCD. Three subfamilies of KCa channels were revealed: the high Ca2+-binding affinity small-conductance SK channels, SK1and SK3, the intermediate conductance channel, IK1, and the low Ca2+-binding affinity, BK channel (BKα subunit). Apparent expression levels varied in CNT/CCD where analysis of CCD principal cells (PC) and intercalated cells (IC) demonstrated differential staining: SK1:PCIC, IK1:PC>IC, BKα:PC = IC, and TRPV4:PC>IC. Patch clamp analysis and fluorescence Ca2+ imaging of mCCDcl1 cells demonstrated potent TRPV4-mediated Ca2+ entry and strong functional cross-talk between TRPV4 and KCa channels. TRPV4-mediated Ca2+ influx activated each KCa channel, as evidenced by selective inhibition of KCa channels, with each active KCa channel enhancing Ca2+ entry (due to membrane hyperpolarization). Transepithelial electrical resistance (TEER) analysis of confluent mCCDcl1 cells grown on permeable supports further demonstrated this cross-talk where TRPV4 activation induce a decrease in TEER which was partially restored upon selective inhibition of each KCa channel. It is concluded that SK1/SK3 and IK1 are highly expressed along with BKα in CNT and CCD and are closely coupled to TRPV4 activation as observed in mCCDcl1 cells. The data support a model in CNT/CCD segments where strong cross talk between TRPV4-mediated Ca2+ influx and each KCa channel leads to enhance Ca2+ entry which will support activation of the low Ca2+-binding affinity BK channel to promote BK-mediated K+ secretion.

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

USGS Publications Warehouse

Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

2016-01-01

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE.

PubMed

Ahlin, E; Mathsson, L; Eloranta, M-L; Jonsdottir, T; Gunnarsson, I; Rönnblom, L; Rönnelid, J

2012-05-01

To what extent different autoantibodies accumulate in systemic lupus erythematosus (SLE) immune complexes (ICs), and whether such accumulation is associated with disease activity has been investigated. ICs were isolated from SLE sera by both polyethylene glycol (PEG) precipitation and C1q-binding. Autoantibody specificities were determined using a lineblot assay quantified by densitometry. To compare the relative levels of autoantibodies, levels were normalized to the total levels of IgG measured by ELISA in sera and parallel ICs. Samples were investigated both in a cross-sectional design as well as in a paired design with samples obtained during both active and inactive SLE. All investigated autoantibody specificities except anti-dsDNA were enriched in circulating ICs as compared with parallel sera. The group of antibodies against RNA-associated antigens (anti-RNP/Sm, anti-Sm, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La) all exhibited higher median enrichment than the DNA-associated (anti-dsDNA, anti-histones, anti-nucleosomes) or cytoplasmic (anti-ribosomal P) antigens. In particular autoantibodies against RNP/Sm and SSA/Ro52 had the highest degree of enrichment in SLE PEG precipitates. These findings were corroborated by analysis of autoantibody content in C1q-bound ICs. There was no difference in degree of IC accumulation of the investigated autoantibodies during active and inactive SLE. Our findings demonstrate a difference in enrichment between autoantibodies against RNA- and DNA-associated autoantigens in isolated SLE IC, suggesting that the RNA-associated autoantibodies are more prone to form circulating ICs in SLE, in contrast to antibodies against DNA-associated autoantigens such as dsDNA. These finding have implications in understanding mechanisms of differential autoantibody accumulation in target organs in SLE.

Intra- and extra-capsular hip fractures in the elderly: Two different pathologies?

PubMed

Dinamarca-Montecinos, J L; Prados-Olleta, N; Rubio-Herrera, R; Castellón-Sánchez del Pino, A; Carrasco-Buvinic, A

2015-01-01

To compare intracapsular (IC) and extracapsular (EC) hip fractures (HIF) in elderly patients in order to determine if they are different pathologies. Longitudinal, observational, descriptive, analytical prospective design, using a non-probabilistic sample from a full sample collection with 647 subjects (male and female), of 60 or more years old, admitted with HIF to the Department of Orthopedics and Traumatology of the Hospital, between January 1, 2010 and December 31, 2012. Follow-up was for 1 year post HIF. Socio-demographic, etiological, developmental, therapeutic and prognostic variables are compared. This is the first study on this subject with Latin American population. EC HIF incidence was superior to IC, contrary to that published in European/American populations. There are significant differences in etiological variables (χ(2)=6.34, p<0.042), with traumatic etiology in EC and non-traumatic in IC. There are also differences in therapeutic interventions performed (osteosynthesis for EC, arthroplasty for IC), with the decision on not to operate being lower in IC (both p<0.0000). The variables associated with the decision on not to perform surgery are age, etiology and postoperative mortality. The results are similar to other studies, adding the IC association with non-traumatic origin, in particular the trend of statistical association between IC and non-primary osteoporotic pathology (neoplasms, renal osteodystrophy, primary hyperparathyroidism). A further analysis was performed on the differences between Latin American and European/American populations in the incidence of either type of HIF. There are important etiological and therapeutic differences between IC and EC HIF; therefore it would be advisable to consider them as distinct disease entities. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

HIV-Related discrimination in European health care settings.

PubMed

Nöstlinger, Christiana; Rojas Castro, Daniela; Platteau, Tom; Dias, Sonia; Le Gall, Jean

2014-03-01

This cross-sectional European study assessed self-reported HIV-related discrimination and its associated factors in health care settings. Socio-demographics, health status, support needs relating to sexual and reproductive health (SRH), and self-reported HIV-related discrimination were measured using an anonymous survey in a sample of 1549 people living with HIV from 14 countries. Thirty-two per cent of the participants had experienced HIV-related discrimination during the previous 3 years; almost half of them felt discriminated against by health care providers. For this type of discrimination, logistic regression analysis revealed significant associations with not being a migrant (OR: 2.0; IC 1.0-3.7; p<0.05), having been forced into sexual activities (OR: 1.6; IC 1.2-2.2; p<0.001), reporting lack of time to discuss SRH during service provision (OR: 1.7; IC 1.0-2.7; p<0.05), and insufficient openness among service providers to discuss SRH (OR: 2.0; IC 1.1-3.4; p<0.05). Other significant associations related to unmet support needs on safer sex practices (OR: 1.8; IC 1.0-3.2; p<0.05), partner communication about sexuality (OR: 2.0; IC 1.1-3.4; p<0.05), and prevention of sexually transmitted infections (OR: 1.7; IC 1.0-3.0; p<0.05). Female gender had a protective effect (OR: 0.2; IC 0.0-0.9; p<0.05). Being denied the opportunity to discuss SRH may translate in feelings of discrimination. Improving health care providers' communication skills, and fostering openness about SRH topics in HIV care could contribute to destigmatization of PLHIV.

Notch signaling regulates the responses of lipopolysaccharide-stimulated macrophages in the presence of immune complexes.

PubMed

Wongchana, Wipawee; Kongkavitoon, Pornrat; Tangtanatakul, Pattarin; Sittplangkoon, Chutamath; Butta, Patcharavadee; Chawalitpong, Supatta; Pattarakankul, Thitiporn; Osborne, Barbara A; Palaga, Tanapat

2018-01-01

Macrophages exhibit diverse effector phenotypes depending on the stimuli and their microenvironment. Classically activated macrophages are primed with interferon (IFN)γ and stimulated with pathogen-associated molecular patterns. They produce inflammatory mediators and inflammatory cytokines, such as IL-12. In the presence of immune complexes (ICs), activated macrophages have decreased IL-12 production and increased IL-10 production and presumably act as regulatory macrophages. Notch signaling has been shown to regulate the effector functions of classically activated macrophages. In this study, we investigated whether Notch signaling is active in lipopolysaccharide (LPS)-stimulated macrophages in the presence of ICs. LPS/IC stimulation increased the level of cleaved Notch1 in murine macrophages, while IC stimulation alone did not. Delta-like 4, but not Jagged1, was responsible for generating cleaved Notch1. The activation of Notch signaling by LPS/ICs depended upon NF-κB and MEK/Erk pathway activation. Macrophages with the targeted deletion of Rbpj, which encodes a DNA-binding protein central to canonical Notch signaling, produced significantly less IL-10 upon LPS/IC stimulation. A similar impact on IL-10 production was observed when Notch signaling was inhibited with a gamma-secretase inhibitor (GSI). Defects in NF-κB p50 nuclear localization were observed in GSI-treated macrophages and in Rbpj-/- macrophages, suggesting cross-regulation between the Notch and NF-κB pathways. Transcriptomic analysis revealed that Notch signaling regulates the transcription of genes involved in the cell cycle, macrophage activation, leukocyte migration and cytokine production in LPS/IC-stimulated macrophages. Taken together, these results suggest that the Notch signaling pathway plays an important role in regulating the functions of macrophages activated by LPS and ICs.

Innovative Magnetic-Field Array Probe for TRUST Integrated Circuits

DTIC Science & Technology

2017-03-01

real-time an IC device. This non-invasive solution is cost effective, with a small form factor. Keywords: Electromagnetic radiation; Near-Field...solicitation was to design, develop and fabricate a low cost electromagnetic probe array for ICs counterfeit. The probe array should operate in the near...Our overall effort was focus on modeling, designing, fabricating, and utilizing novel electromagnetic probes for the analysis, characterization

Cost-effectiveness of roflumilast in combination with bronchodilator therapies in patients with severe and very severe COPD in Switzerland

PubMed Central

Samyshkin, Yevgeniy; Schlunegger, Michael; Haefliger, Susan; Ledderhose, Sabine; Radford, Matthew

2013-01-01

Objective Chronic obstructive pulmonary disease (COPD) represents a burden on patients and health systems. Roflumilast, an oral, selective phosphodiesterase-4-inhibitor reduces exacerbations and improves lung function in severe/very severe COPD patients with a history of exacerbations. This study aimed to estimate the lifetime cost and outcomes of roflumilast added-on to commonly used COPD regimens in Switzerland. Methods A Markov cohort model was developed to simulate COPD progression in patients with disease states of severe, very severe COPD, and death. The exacerbation rate was assumed to be two per year in severe COPD. COPD progression rates were drawn from the published literature. Efficacy was expressed as relative ratios of exacerbation rates associated with roflumilast, derived from a mixed-treatment comparison. A cost-effectiveness analysis was conducted for roflumilast added to long-acting muscarinic antagonists (LAMA), long-acting β2-agonist/ inhaled corticosteroids (LABA/ICS), and LAMA + LABA/ICS. The analysis was conducted from the Swiss payer perspective, with costs and outcomes discounted at 2.5% annually. Parameter uncertainties were explored in one-way and probabilistic sensitivity analyses. Results In each of the comparator regimens mean life expectancy was 9.28 years and quality-adjusted life years (QALYs) gained were 6.19. Mean estimated lifetime costs per patient in the comparator arms were CHF 83,364 (LAMA), CHF 88,161 (LABA/ICS), and CHF 95,564 (LAMA + LABA/ICS) respectively. Adding roflumilast resulted in a mean cost per patient per lifetime of CHF 86,754 (LAMA + roflumilast), CHF 91,470 (LABA/ICS + roflumilast), and CHF 99,364 (LAMA + LABA/ICS + roflumilast), respectively. Life-expectancy and quality-adjusted life-expectancy were 9.63 years and 6.47 QALYs (LAMA + roflumilast), 9.64 years and 6.48 QALYs (LABA/ICS + roflumilast), and 9.63 years and 6.47 QALYs (LAMA + LABA/ ICS + roflumilast). Incremental cost-effectiveness ratios were CHF 12,313, CHF 11,456, and CHF 13,671 per QALY when roflumilast was added to the three regimens. Conclusion Treatment with roflumilast is estimated to reduce the health and economic burden of COPD exacerbations and represent a cost-effective treatment option for patients with frequent exacerbations in Switzerland. PMID:23386787

Validation and Clinical Utility of the hERG IC50:Cmax Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis.

PubMed

Lehmann, David F; Eggleston, William D; Wang, Dongliang

2018-03-01

Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C max ) is used during drug development to screen out chemical entities likely to cause TdP. To validate the use of the hERG IC50:C max ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. Medline (between 1966 and March 2017) was accessed for hERG IC50 and C max values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. Negligible risk drugs were defined by an hERG IC50:C max ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). The hERG IC50:C max ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. The hERG IC50:C max ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C max ratio for clinical decision making in instances of drug selection where TdP risk is a concern. © 2018 Pharmacotherapy Publications, Inc.

Effect of Embedded Piezoelectric Sensors on Fracture Toughness and Fatigue Resistance of Composite Laminates Under Mode I Loading

NASA Technical Reports Server (NTRS)

Murri, Gretchen B.

2006-01-01

Double-cantilevered beam (DCB) specimens of a glass/epoxy composite material with embedded piezoelectric sensors were tested both statically and under fatigue loading to determine the effect of the embedded material on the Mode I fracture toughness and fatigue resistance compared to baseline data without the embedded elements. A material known as LaRC-Macrofiber Composite (LaRC-MFC (TradeMark)), or MFC, was embedded at the midplane of the specimen during the layup. Specimens were manufactured with the embedded MFC material either at the loaded end of the specimen to simulate an initial delamination; or with the MFC material located at the delaminating interface, with a Teflon film at the loaded end to simulate an initial delamination. There were three types of specimens with the embedded material at the delaminating interface: co-cured with no added adhesive; cured with a paste adhesive applied to the embedded element; or cured with a film adhesive added to the embedded material. Tests were conducted with the sensors in both the passive and active states. Results were compared to baseline data for the same material without embedded elements. Interlaminar fracture toughness values (G(sub Ic)) for the passive condition showed little change when the MFC was at the insert end. Passive results varied when the MFC was at the delaminating interface. For the co-cured case and with the paste adhesive, G(sub Ic) decreased compared to the baseline toughness, whereas, for the film adhesive case, G(sub Ic) was significantly greater than the baseline toughness, but the failure was always catastrophic. When the MFC was in the active state, G(sub Ic) was generally lower compared to the passive results. Fatigue tests showed little effect of the embedded material whether it was active or passive compared to baseline values.

Low level tumor necrosis factor-alpha protects cardiomyocytes against high level tumor necrosis factor-alpha: brief insight into a beneficial paradox.

PubMed

Cacciapaglia, Fabio; Salvatorelli, Emanuela; Minotti, Giorgio; Afeltra, Antonella; Menna, Pierantonio

2014-12-01

Whether tumor necrosis factor-alpha (TNFα) caused beneficial or detrimental cardiovascular effects remains poorly defined. Anti-TNFα agents improved cardiac end points in chronic rheumatic diseases characterized by progressive deterioration of cardiac function. In contrast, anti-TNFα agents did not always improve but actually worsened cardiac function in non-rheumatic patients with heart failure (HF), in spite of that HF usually accompanies with high circulating levels of TNFα. To shed light on these mixed findings, we characterized the effects of TNFα in H9c2 cardiomyocytes. Cells were incubated for 24 h with increasing concentrations of TNFα, hydrogen peroxide, aminotriazole, or etoposide. Posttreatment cell viability was assessed by antimycin A-inhibitable reduction of 3-(4,dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and the IC50 value of each test compound was defined. H9c2 cells were also preconditioned with a low non-toxic concentration of TNFα and then re-challenged with increasing concentrations of TNFα and other stressor agents. In re-challenge experiments, all of the IC50 values increased significantly, with the IC50 value of TNFα increasing approximately 16-fold. TNFα preconditioning increased cardiomyocytes shedding of the external portion of transmembrane type 1 and type 2 TNFα receptors [(soluble TNFα receptors (sTNFR)]. Levels of survival-oriented soluble TNFR2 (sTNFR2) always exceeded those of death-oriented sTNFR1. When exposed to TNFα at its IC50 value, preconditioned cardiomyocytes showed an increased release of sTNFR2 but not sTNFR1. These results denoted that preconditioning by "low TNFα" helped cardiomyocyte to withstand toxicity from "high TNFα" or other agents. These results also suggested that beneficial or detrimental effects of anti-TNFα agents might well depend on whether these agents spared or intercepted discrete amounts of TNFα that preconditioned cardiomyocytes and made them more resistant to high concentrations of TNFα.

Sex Differences in Gamma Band Functional Connectivity Between the Frontal Lobe and Cortical Areas During an Auditory Oddball Task, as Revealed by Imaginary Coherence Assessment.

PubMed

Fujimoto, Toshiro; Okumura, Eiichi; Kodabashi, Atsushi; Takeuchi, Kouzou; Otsubo, Toshiaki; Nakamura, Katsumi; Yatsushiro, Kazutaka; Sekine, Masaki; Kamiya, Shinichiro; Shimooki, Susumu; Tamura, Toshiyo

2016-01-01

We studied sex-related differences in gamma oscillation during an auditory oddball task, using magnetoencephalography and electroencephalography assessment of imaginary coherence (IC). We obtained a statistical source map of event-related desynchronization (ERD) / event-related synchronization (ERS), and compared females and males regarding ERD / ERS. Based on the results, we chose respectively seed regions for IC determinations in low (30-50 Hz), mid (50-100 Hz) and high gamma (100-150 Hz) bands. In males, ERD was increased in the left posterior cingulate cortex (CGp) at 500 ms in the low gamma band, and in the right caudal anterior cingulate cortex (cACC) at 125 ms in the mid-gamma band. ERS was increased in the left rostral anterior cingulate cortex (rACC) at 375 ms in the high gamma band. We chose the CGp, cACC and rACC as seeds, and examined IC between the seed and certain target regions using the IC map. IC changes depended on the height of the gamma frequency and the time window in the gamma band. Although IC in the mid and high gamma bands did not show sex-specific differences, IC at 30-50 Hz in males was increased between the left rACC and the frontal, orbitofrontal, inferior temporal and fusiform target regions. Increased IC in males suggested that males may acomplish the task constructively, analysingly, emotionally, and by perfoming analysis, and that information processing was more complicated in the cortico-cortical circuit. On the other hand, females showed few differences in IC. Females planned the task with general attention and economical well-balanced processing, which was explained by the higher overall functional cortical connectivity. CGp, cACC and rACC were involved in sex differences in information processing and were likely related to differences in neuroanatomy, hormones and neurotransmitter systems.

The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA.

PubMed Central

Kaetzel, C S; Robinson, J K; Chintalacharuvu, K R; Vaerman, J P; Lamm, M E

1991-01-01

The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA. Images PMID:1924341

Determination of the appropriate catheter length and place for needle thoracostomy by using computed tomography scans of pneumothorax patients.

PubMed

Akoglu, Haldun; Akoglu, Ebru Unal; Evman, Serdar; Akoglu, Tayfun; Altinok, Arzu Denizbasi; Guneysel, Ozlem; Onur, Ozge Ecmel; Eroglu, Serkan Emre

2013-09-01

The primary goal of this study was to compare the chest wall thicknesses (CWT) at the 2nd intercostal space (ICS) at the mid-clavicular line (MCL) and 5th ICS at the mid-axillary line (MAL) in a population of patients with a CT confirmed pneumothorax (PTX). This result will help physicians to determine the optimum needle thoracostomy (NT) puncture site in patients with a PTX. All trauma patients who presented consecutively to A&E over a 12-month period were included. Among all the trauma patients with a chest CT (4204 patients), 160 were included in the final analysis. CWTs were measured at both sides and were compared in all subgroup of patients. The average CWT for men on the 2nd ICS-MCL was 38mm and for women was 52mm; on the other hand, on the 5th ICS-MAL was 33mm for men and 38mm for women. On the 2nd ICS-MCL 17% of men and 48% of women; on the 5th ICS-MAL 13% of men and 33% of women would be inaccessible with a routine 5-cm catheter. Patients with trauma, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 2nd ICS-MCL. Patients with trauma, lung contusion, sternum fracture, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 5th ICS-MAL. This study confirms that a 5.0-cm catheter would be unlikely to access the pleural space in at least 1/3 of female and 1/10 of male Turkish trauma patients, regardless of the puncture site. If NT is needed, the 5th ICS-MAL is a better option for a puncture site with thinner CWT. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Influence of Sn Orientation on the Electromigration of Idealized Lead-free Interconnects

NASA Astrophysics Data System (ADS)

Linares, Xioranny

As conventional lead solders are being replaced by Pb-free solders in electronic devices, the reliability of solder joints in integrated circuits (ICs) has become a high concern. Due to the miniaturization of ICs and consequently solder joints, the current density through the solder interconnects has increased causing electrical damage known as electromigration. Electromigration, atomic and mass migration due to high electron currents, is one of the most urgent reliability issues delaying the implementation of Pb-free solder materials in electronic devices. The research on Pb-free solders has mainly focused on the qualitative understanding of failure by electromigration. There has been little progress however, on the quantitative analysis of electromigration because of the lack of available material parameters, such as the effective charge, (z*), the driving force for electromigration. The research herein uses idealized interconnects to measure the z* of electromigration of Cu in Sn-3.0Ag-0.5Cu (SAC305) alloy under different experimental conditions. Planar SAC 305 interconnects were sandwiched between two Cu pads and subject to uniaxial current. The crystallographic orientation of Sn in these samples were characterized with electron backscatter diffraction (EBSD) and wavelength dispersive spectroscopy (WDS) before and after electromigration testing. Results indicate that samples with the c-axis aligned perpendicular to current flow, polycrystalline, and those with a diffusion barrier on the cathode side all inhibit the growth of intermetallic compounds (IMC). The effective charge values of Cu in SAC 305 under the different conditions tested were quantified for the first time and included in this dissertation. The following research is expected to help verify and improve the electromigration model and identify the desirable conditions to inhibit damage by electromigration in Pb-free solder joints.

Mechanical Strength and Failure Characterization of Sn-Ag-Cu Intermetallic Compound Joints at the Microscale

NASA Astrophysics Data System (ADS)

Ladani, Leila; Razmi, Jafar

2012-03-01

Continuous miniaturization of microelectronic devices has led the industry to develop interconnects on the order of a few microns for advanced superhigh-density and three-dimensional integrated circuits (3D ICs). At this scale, interconnects that conventionally consist of solder material will completely transform to intermetallic compounds (IMCs) such as Cu6Sn5. IMCs are brittle, unlike conventional solder materials that are ductile in nature; therefore, IMCs do not experience large amounts of plasticity or creep before failure. IMCs have not been fully characterized, and their mechanical and thermomechanical reliability is questioned. This study presents experimental efforts to characterize such material. Sn-based microbonds are fabricated in a controlled environment to assure complete transformation of the bonds to Cu6Sn5 IMC. Microstructural analysis including scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) is utilized to determine the IMC material composition and degree of copper diffusion into the bond area. Specimens are fabricated with different bond thicknesses and in different configurations for various tests. Normal strength of the bonds is measured utilizing double cantilever beam and peeling tests. Shear tests are conducted to quantify the shear strength of the material. Four-point bending tests are conducted to measure the fracture toughness and critical energy release rate. Bonds are fabricated in different sizes, and the size effect is investigated. The shear strength, normal strength, critical energy release rate, and effect of bond size on bond strength are reported.

Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

PubMed

Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

2013-05-01

Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural abnormalities are, in part, caused by up-regulation of dynein IC2-GR-COX-1 signaling, which may be a novel therapeutic target for NF1.

Image Noise, CNR, and Detectability of Low-Contrast, Low-Attenuation Liver Lesions in a Phantom: Effects of Radiation Exposure, Phantom Size, Integrated Circuit Detector, and Iterative Reconstruction.

PubMed

Goenka, Ajit H; Herts, Brian R; Dong, Frank; Obuchowski, Nancy A; Primak, Andrew N; Karim, Wadih; Baker, Mark E

2016-08-01

Purpose To assess image noise, contrast-to-noise ratio (CNR) and detectability of low-contrast, low-attenuation liver lesions in a semianthropomorphic phantom by using either a discrete circuit (DC) detector and filtered back projection (FBP) or an integrated circuit (IC) detector and iterative reconstruction (IR) with changes in radiation exposure and phantom size. Materials and Methods An anthropomorphic phantom without or with a 5-cm-thick fat-mimicking ring (widths, 30 and 40 cm) containing liver inserts with four spherical lesions was scanned with five exposure settings on each of two computed tomography scanners, one equipped with a DC detector and the other with an IC detector. Images from the DC and IC detector scanners were reconstructed with FBP and IR, respectively. Image noise and lesion CNR were measured. Four radiologists evaluated lesion presence on a five-point diagnostic confidence scale. Data analyses included receiver operating characteristic (ROC) curve analysis and noninferiority analysis. Results The combination of IC and IR significantly reduced image noise (P < .001) (with the greatest reduction in the 40-cm phantom and at lower exposures) and improved lesion CNR (P < .001). There was no significant difference in area under the ROC curve between detector-reconstruction combinations at fixed exposure for either phantom. Reader accuracy with IC-IR was noninferior at 50% (100 mAs [effective]) and 25% (300 mAs [effective]) exposure reduction for the 30- and 40-cm phantoms, respectively (adjusted P < .001 and .04 respectively). IC-IR improved readers' confidence in the presence of a lesion (P = .029) independent of phantom size or exposure level. Conclusion IC-IR improved objective image quality and lesion detection confidence but did not result in superior diagnostic accuracy when compared with DC-FBP. Moderate exposure reductions maintained comparable diagnostic accuracy for both detector-reconstruction combinations. Lesion detection in the 40-cm phantom was inferior at smaller exposure reduction than in the 30-cm phantom. (©) RSNA, 2016 Online supplemental material is available for this article.

Simulation of local convective rainfall over metropolitan area on 16 August 2015 using high resolution model

NASA Astrophysics Data System (ADS)

Lee, Y. H.; Min, K. H.

2017-12-01

We investigated the ability of high-resolution numerical weather prediction (NWP) model (nested grid spacing at 500 m) in simulating convective precipitation event over the Seoul metropolitan area on 16 August 2015. Intense rainfall occurred from 0930 UTC to 1030 UTC and subsequent trailing precipitation lasted until 1400 UTC. The synoptic condition for the convective event was characterized by a large value of convective available potential energy (CAPE) at the outer edge of a meso-high pressure system. Observational analysis showed that triggering mechanism for convective rainfall was provided by the convergence of northeasterly wind which was driven by a cold pool in the northeastern Kyonggi province. The cold pool formed after heavy rain occurred in northeastern Kyonggi province at 0500UTC. Several experiments were performed in order to evaluate the sensitivity of different initial conditions (IC12, IC18, IC00, IC06) and the impact of data assimilation (IC06A) on simulating the convective event. The quantitative precipitation forecasts (QPF) appeared to vary widely among the experiments, depending on the timing of ICs that were chosen. QPF amount was underestimated in all experiments when data assimilation was not performed. Among the four experiments, QPF amounts and locations were better simulated in the 1200 UTC 15 August (IC12) run due to large values of CAPE in late afternoon and the presence of low-level convergence zone in the metropolitan area. Although 0600 UTC 16 August (IC06) run simulated the largest CAPE in late afternoon, the location and amount of heavy rainfall were significantly different from observations. IC06 did not simulate the convergence of low-level wind associated with the mesoscale cold pool. However, when assimilation of surface observations and radar data at 0600 UTC was performed (IC06A), the simulation reproduced the location and amount of rainfall reasonably well, indicating that high-resolution NWP model with data assimilation can predict the local convective precipitation event with a short-life time (1 3 hours) effectively within 6 hours.

Visible light laser voltage probing on thinned substrates

DOEpatents

Beutler, Joshua; Clement, John Joseph; Miller, Mary A.; Stevens, Jeffrey; Cole, Jr., Edward I.

2017-03-21

The various technologies presented herein relate to utilizing visible light in conjunction with a thinned structure to enable characterization of operation of one or more features included in an integrated circuit (IC). Short wavelength illumination (e.g., visible light) is applied to thinned samples (e.g., ultra-thinned samples) to achieve a spatial resolution for laser voltage probing (LVP) analysis to be performed on smaller technology node silicon-on-insulator (SOI) and bulk devices. Thinning of a semiconductor material included in the IC (e.g., backside material) can be controlled such that the thinned semiconductor material has sufficient thickness to enable operation of one or more features comprising the IC during LVP investigation.

Real-time diagnostics for a reusable rocket engine

NASA Technical Reports Server (NTRS)

Guo, T. H.; Merrill, W.; Duyar, A.

1992-01-01

A hierarchical, decentralized diagnostic system is proposed for the Real-Time Diagnostic System component of the Intelligent Control System (ICS) for reusable rocket engines. The proposed diagnostic system has three layers of information processing: condition monitoring, fault mode detection, and expert system diagnostics. The condition monitoring layer is the first level of signal processing. Here, important features of the sensor data are extracted. These processed data are then used by the higher level fault mode detection layer to do preliminary diagnosis on potential faults at the component level. Because of the closely coupled nature of the rocket engine propulsion system components, it is expected that a given engine condition may trigger more than one fault mode detector. Expert knowledge is needed to resolve the conflicting reports from the various failure mode detectors. This is the function of the diagnostic expert layer. Here, the heuristic nature of this decision process makes it desirable to use an expert system approach. Implementation of the real-time diagnostic system described above requires a wide spectrum of information processing capability. Generally, in the condition monitoring layer, fast data processing is often needed for feature extraction and signal conditioning. This is usually followed by some detection logic to determine the selected faults on the component level. Three different techniques are used to attack different fault detection problems in the NASA LeRC ICS testbed simulation. The first technique employed is the neural network application for real-time sensor validation which includes failure detection, isolation, and accommodation. The second approach demonstrated is the model-based fault diagnosis system using on-line parameter identification. Besides these model based diagnostic schemes, there are still many failure modes which need to be diagnosed by the heuristic expert knowledge. The heuristic expert knowledge is implemented using a real-time expert system tool called G2 by Gensym Corp. Finally, the distributed diagnostic system requires another level of intelligence to oversee the fault mode reports generated by component fault detectors. The decision making at this level can best be done using a rule-based expert system. This level of expert knowledge is also implemented using G2.

Analysis of Vibratory Driven Pile.

DTIC Science & Technology

1987-10-01

DF ) . Deiier. CO.I Smioak. F)ctl er. ( (C (odite IS. Port IlierICeme. (A; (odeC 155. Port I Iienemeri. (A..: COdIC 156. P’oll F Ficiciiic. (NA...23C;~.i~ ode F)LNA OF19424(1.\\ N i’i nu, toil. F C: ocO’’lK \\;~i~oi .(d ( CGARF R&D(’ Fijbrir\\. (irotoit CI( (I INWI, IANI COdIC S.31F, Norfolk.V

Analysis of Instructional Support Elements for an Online, Educational Simulation on Active Listening for Women Graduate Students in Science and Engineering

ERIC Educational Resources Information Center

Bernstein, Bianca L.; Bekki, Jennifer M.; Wilkins, Kerrie G.; Harrison, Caroline J.

2016-01-01

Strong interpersonal communication skills (ICS) are critical for educational and career success, but effective and widely accessible training systems are not available. This paper describes a 2 × 2 × 2 experimental study of an online, educational simulation for practice with the ICS of active listening. The simulation was customized for women…

The planetary nebula IC 4776 and its post-common-envelope binary central star

NASA Astrophysics Data System (ADS)

Sowicka, Paulina; Jones, David; Corradi, Romano L. M.; Wesson, Roger; García-Rojas, Jorge; Santander-García, Miguel; Boffin, Henri M. J.; Rodríguez-Gil, Pablo

2017-11-01

We present a detailed analysis of IC 4776, a planetary nebula displaying a morphology believed to be typical of central star binarity. The nebula is shown to comprise a compact hourglass-shaped central region and a pair of precessing jet-like structures. Time-resolved spectroscopy of its central star reveals a periodic radial velocity variability consistent with a binary system. Whilst the data are insufficient to accurately determine the parameters of the binary, the most likely solutions indicate that the secondary is probably a low-mass main-sequence star. An empirical analysis of the chemical abundances in IC 4776 indicates that the common-envelope phase may have cut short the asymptotic giant branch evolution of the progenitor. Abundances calculated from recombination lines are found to be discrepant by a factor of approximately 2 relative to those calculated using collisionally excited lines, suggesting a possible correlation between low-abundance discrepancy factors and intermediate-period post-common-envelope central stars and/or Wolf-Rayet central stars. The detection of a radial velocity variability associated with the binarity of the central star of IC 4776 may be indicative of a significant population of (intermediate-period) post-common-envelope binary central stars that would be undetected by classic photometric monitoring techniques.

A comparison of independent component analysis algorithms and measures to discriminate between EEG and artifact components.

PubMed

Dharmaprani, Dhani; Nguyen, Hoang K; Lewis, Trent W; DeLosAngeles, Dylan; Willoughby, John O; Pope, Kenneth J

2016-08-01

Independent Component Analysis (ICA) is a powerful statistical tool capable of separating multivariate scalp electrical signals into their additive independent or source components, specifically EEG or electroencephalogram and artifacts. Although ICA is a widely accepted EEG signal processing technique, classification of the recovered independent components (ICs) is still flawed, as current practice still requires subjective human decisions. Here we build on the results from Fitzgibbon et al. [1] to compare three measures and three ICA algorithms. Using EEG data acquired during neuromuscular paralysis, we tested the ability of the measures (spectral slope, peripherality and spatial smoothness) and algorithms (FastICA, Infomax and JADE) to identify components containing EMG. Spatial smoothness showed differentiation between paralysis and pre-paralysis ICs comparable to spectral slope, whereas peripherality showed less differentiation. A combination of the measures showed better differentiation than any measure alone. Furthermore, FastICA provided the best discrimination between muscle-free and muscle-contaminated recordings in the shortest time, suggesting it may be the most suited to EEG applications of the considered algorithms. Spatial smoothness results suggest that a significant number of ICs are mixed, i.e. contain signals from more than one biological source, and so the development of an ICA algorithm that is optimised to produce ICs that are easily classifiable is warranted.

Possible occurrence of paraesthesia in patients taking norethisterone: an analysis on the WHO Global Individual Case Reports database (VigiBase).

PubMed

Buccellato, Elena; Biagi, Chiara; Vaccheri, Alberto; Melis, Mauro; Montanaro, Nicola; Motola, Domenico

2013-09-01

Progestogens are widely used to treat a large number of common conditions. We aimed to investigate a potential signal concerning progestogens and paraesthesia. Data were obtained from the VigiBase, the WHO Global Individual Case Safety Reports (ICSR) database, which is maintained by the Uppsala Monitoring Centre. We collected all suspected reports of paraesthesia associated with oral progestogens, reported between January 1972 and June 2012 and classified in VigiBase according to WHO-Adverse Reaction Terminology critical term 'paraesthesia'. A disproportionality analysis was conducted using the Information Component (IC) and the standard deviation (IC025) as a measure. Out of the total number of reports collected in the VigiBase (7,332,991), paraesthesia was associated with progestogen therapy in 920 reports, coming from 22 countries. Progestogens had the highest number of suspected reports (n = 864) than the other Anatomical Therapeutic Chemical (ATC) considered. Only norethisterone was associated with paraesthesia with positive IC (0.47) and IC025 (0.02). Norethisterone-associated paraesthesia appears to be a rare outcome. However, the widespread use of progestogens in medical practice suggests that it is a complaint that can affect a large number of women. Since paraesthesia can be caused by several drugs, clinicians should consider that it may be also caused by norethisterone.

Managing Rock and Paleomagnetic Data Flow with the MagIC Database: from Measurement and Analysis to Comprehensive Archive and Visualization

NASA Astrophysics Data System (ADS)

Koppers, A. A.; Minnett, R. C.; Tauxe, L.; Constable, C.; Donadini, F.

2008-12-01

The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by rock and paleomagnetic data. The goal of MagIC is to archive all measurements and derived properties for studies of paleomagnetic directions (inclination, declination) and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Organizing data for presentation in peer-reviewed publications or for ingestion into databases is a time-consuming task, and to facilitate these activities, three tightly integrated tools have been developed: MagIC-PY, the MagIC Console Software, and the MagIC Online Database. A suite of Python scripts is available to help users port their data into the MagIC data format. They allow the user to add important metadata, perform basic interpretations, and average results at the specimen, sample and site levels. These scripts have been validated for use as Open Source software under the UNIX, Linux, PC and Macintosh© operating systems. We have also developed the MagIC Console Software program to assist in collating rock and paleomagnetic data for upload to the MagIC database. The program runs in Microsoft Excel© on both Macintosh© computers and PCs. It performs routine consistency checks on data entries, and assists users in preparing data for uploading into the online MagIC database. The MagIC website is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual FlashMap interface to browse and select locations. Users can also browse the database by data type (inclination, intensity, VGP, hysteresis, susceptibility) or by data compilation to view all contributions associated with previous databases, such as PINT, GMPDB or TAFI or other user-defined compilations. Query results are displayed in a digestible tabular format allowing the user to descend from locations to sites, samples, specimens and measurements. At each stage, the result set can be saved and, when supported by the data, can be visualized by plotting global location maps, equal area, XY, age, and depth plots, or typical Zijderveld, hysteresis, magnetization and remanence diagrams.

Solving the challenges of data preprocessing, uploading, archiving, retrieval, analysis and visualization for large heterogeneous paleo- and rock magnetic datasets

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A. A.; Tauxe, L.; Constable, C.; Jarboe, N. A.

2011-12-01

The Magnetics Information Consortium (MagIC) provides an archive for the wealth of rock- and paleomagnetic data and interpretations from studies on natural and synthetic samples. As with many fields, most peer-reviewed paleo- and rock magnetic publications only include high level results. However, access to the raw data from which these results were derived is critical for compilation studies and when updating results based on new interpretation and analysis methods. MagIC provides a detailed metadata model with places for everything from raw measurements to their interpretations. Prior to MagIC, these raw data were extremely cumbersome to collect because they mostly existed in a lab's proprietary format on investigator's personal computers or undigitized in field notebooks. MagIC has developed a suite of offline and online tools to enable the paleomagnetic, rock magnetic, and affiliated scientific communities to easily contribute both their previously published data and data supporting an article undergoing peer-review, to retrieve well-annotated published interpretations and raw data, and to analyze and visualize large collections of published data online. Here we present the technology we chose (including VBA in Excel spreadsheets, Python libraries, FastCGI JSON webservices, Oracle procedures, and jQuery user interfaces) and how we implemented it in order to serve the scientific community as seamlessly as possible. These tools are now in use in labs worldwide, have helped archive many valuable legacy studies and datasets, and routinely enable new contributions to the MagIC Database (http://earthref.org/MAGIC/).

Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

PubMed

Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

2012-09-01

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

Kinetic Modeling of PET Data Without Blood Sampling

NASA Astrophysics Data System (ADS)

Bentourkia, M.

2005-06-01

In positron emission tomography (PET) imaging, application of kinetic modeling always requires an input curve (IC) together with the PET data. The IC can be obtained by means of external blood sampling or, in the case of cardiac studies, by means of a region-of-interest (ROI) drawn on the blood pool. It is, however, very unsuitable to withdraw and to analyze blood samples, and in small animals, these operations become difficult, while ICs determined from ROIs are generally contaminated by emissions from neighboring sites, or they are underestimated because of partial volume effect. In this paper, we report a new method to extract kinetic parameters from dynamic PET studies without a priori knowledge of the IC. The method is applied in human brain data measured with fluorodeoxyglucose (FDG) human-brain and in cardiac-rat perfusion studies with /sup 13/N-ammonia and /sup 11/C-acetate. The tissue blood volume (TBV), usually fitted together with the rate constants, is extracted simultaneously with the tissue time activity curves for cardiac studies, while for brain gray matter, TBV is known to be about 4% to 7%. The shape of IC is obtained by means of factor analysis from an ROI drawn around a cardiac tissue or a brain artery. The results show a good correlation (p<0.05) between the cerebral metabolic rate of glucose, myocardial blood flow, and oxygen consumption obtained with the new method in comparison to the usual method. In conclusion, it is possible to apply kinetic modeling without any blood sampling, which significantly simplifies PET acquisition and data analysis.

Synthesis and QSAR study of novel α-methylene-γ-butyrolactone derivatives as antifungal agents.

PubMed

Wu, Yong-Ling; Wang, De-Long; Guo, En-Hui; Song, Shuang; Feng, Jun-Tao; Zhang, Xing

2017-03-01

Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC 50 ) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC 50 =22.91, 18.89μM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R 2 =0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC 50 =18.89μM (against B. cinerea.) but low cytotoxicity with IC 50 =35.4μM (against HepG2 cell line) and IC 50 =68.8μM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Behavioral treatment of chronic insomnia in older adults: does nocturia matter?

PubMed

Tyagi, Shachi; Resnick, Neil M; Perera, Subashan; Monk, Timothy H; Hall, Martica H; Buysse, Daniel J

2014-04-01

To evaluate the impact of nocturia on the therapeutic response of chronic insomnia to behavioral treatment in older adults. Secondary analysis of a randomized clinical trial designed to assess the efficacy of brief behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in 79 community-dwelling older adults with chronic insomnia. For the current analysis, participants were stratified into 2 groups: those with self-reported nocturia at baseline i.e., ≥ 1 void/night (N = 30; 16 IC, 14 BBTI) and those without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and polysomnography. Individuals without baseline nocturia responded well to BBTI with significant decrease in sleep latency, wake after sleep onset, and total sleep time assessed by sleep diary and actigraphy; these changes were significantly greater than those in the IC group. In comparison, changes in the same sleep parameters among participants with nocturia were not significantly different from the IC control. Although BBTI showed significant improvement in sleep quality in groups with and without nocturia (as assessed by PSQI and sleep diary), the effect size of these improvements was larger in those without nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality d = 0.83 vs. 0.51). These secondary analyses suggest that brief behavioral treatment of insomnia may be more efficacious in improving insomnia in participants without nocturia. Addressing nocturia may improve the efficacy of behavioral insomnia treatment.

Is the BTS/SIGN guideline confusing? A retrospective database analysis of asthma therapy.

PubMed

Covvey, Jordan R; Johnston, Blair F; Wood, Fraser; Boyter, Anne C

2013-09-01

The British guideline on the management of asthma produced by the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN) describes five steps for the management of chronic asthma. Combination therapy of a long acting β2-agonist (LABA) and an inhaled corticosteroid (ICS) is recommended as first-line therapy at step 3, although the dose of ICS at which to add a LABA is subject to debate. To classify the inhaled therapy prescribed to patients with asthma in NHS Forth Valley according to two interpretations of the BTS/SIGN guideline and to evaluate the use of combination therapy in this population. A retrospective analysis including patients from 46 general practitioner surgeries was conducted. Patients with physician diagnosed asthma were classified according to the BTS/SIGN guideline based on treatment prescribed during 2008. Patient characteristics were evaluated for the overall step classification, and specifically for therapy in step 3. 12,319 patients were included. Guideline interpretation resulted in a shift of 9.2% of patients (receiving medium-dose ICS alone) between steps 2 and 3. The largest proportion of patients (32.3%) was classified at step 4. Age, sex, smoking status, chronic obstructive pulmonary disease co-morbidity, and utilisation of short-acting β2-agonists and oral corticosteroids all correlated with step; however, no differences in these characteristics were evident between low-dose combination therapy and medium-dose ICS alone at step 3. Further studies are needed to evaluate prescribing decisions in asthma. Guideline recommendations regarding the use of ICS dose escalation versus combination therapy need to be clarified relative to the published evidence.

Determination of the optimal number of components in independent components analysis.

PubMed

Kassouf, Amine; Jouan-Rimbaud Bouveresse, Delphine; Rutledge, Douglas N

2018-03-01

Independent components analysis (ICA) may be considered as one of the most established blind source separation techniques for the treatment of complex data sets in analytical chemistry. Like other similar methods, the determination of the optimal number of latent variables, in this case, independent components (ICs), is a crucial step before any modeling. Therefore, validation methods are required in order to decide about the optimal number of ICs to be used in the computation of the final model. In this paper, three new validation methods are formally presented. The first one, called Random_ICA, is a generalization of the ICA_by_blocks method. Its specificity resides in the random way of splitting the initial data matrix into two blocks, and then repeating this procedure several times, giving a broader perspective for the selection of the optimal number of ICs. The second method, called KMO_ICA_Residuals is based on the computation of the Kaiser-Meyer-Olkin (KMO) index of the transposed residual matrices obtained after progressive extraction of ICs. The third method, called ICA_corr_y, helps to select the optimal number of ICs by computing the correlations between calculated proportions and known physico-chemical information about samples, generally concentrations, or between a source signal known to be present in the mixture and the signals extracted by ICA. These three methods were tested using varied simulated and experimental data sets and compared, when necessary, to ICA_by_blocks. Results were relevant and in line with expected ones, proving the reliability of the three proposed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

PubMed

García-Pascual, Carmen Maria; Ferrero, Hortensia; Juarez, Irene; Martínez, Jessica; Villanueva, Ana; Pozuelo-Rubio, Mercedes; Soengas, Marisol; Tormo, Damiá; Simón, Carlos; Gómez, Raúl; Pellicer, Antonio

2016-02-01

To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC(PEI)] in xenografted human leiomyomas. Heterologous leiomyoma mouse model. University-affiliated infertility center. Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC(PEI)] (n = 8) for 4 weeks. The size of the leiomyoma implants, and cellular proliferation (Ki67), vascularization (PECAM), and apoptosis (OH-ends) assessed by quantitative immunohistochemical/immunofluorescent analysis of the recovered implants. No significant differences were observed in the size of the leiomyoma implants between groups. Vascularization and proliferation were significantly decreased, and apoptosis was increased in the [pIC(PEI)]-treated group versus control. We hypothesize that the antiangiogenic and apoptotic effects exerted by [pIC(PEI)] might lead to a decrease in lesion size in this animal model if the compound is administered for longer periods of time. This study provides promising data on [pIC(PEI)] as a potential novel therapeutic agent against human leiomyoma. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Functionalized chitosan electrospun nanofiber for effective removal of trace arsenate from water

PubMed Central

Min, Ling-Li; Zhong, Lu-Bin; Zheng, Yu-Ming; Liu, Qing; Yuan, Zhi-Huan; Yang, Li-Ming

2016-01-01

An environment-friendly iron functionalized chitosan elctrospun nanofiber (ICS-ENF) was synthesized for trace arsenate removal from water. The ICS-ENF was fabricated by electrospinning a mixture of chitosan, PEO and Fe3+ followed by crosslinking with ammonia vapor. The physicochemical properties of ICS-ENF were characterized by FESEM, TEM-EDX and XRD. The ICS-ENF was found to be highly effective for As(V) adsorption at neutral pH. The As(V) adsorption occurred rapidly and achieved equilibrium within 100 min, which was well fitted by pseudo-second-order kinetics model. The As(V) adsorption decreased with increased ionic strength, suggesting an outer-sphere complexation of As(V) on ICS-ENF. Freundlich model well described the adsorption isotherm, and the maximum adsorption capacity was up to 11.2 mg/g at pH 7.2. Coexisting anions of chloride and sulfate showed negligible influence on As(V) removal, but phosphate and silicate significantly reduced As(V) adsorption by competing for adsorption sites. FTIR and XPS analysis demonstrated –NH, –OH and C–O were responsible for As(V) uptake. ICS-ENF was easily regenerated using 0.003 M NaOH, and the removal rate remained above 98% after ten successively adsorption-desorption recycles. This study extends the potential applicability of electrospun nanofibers for water purification and provides a promising approach for As(V) removal from water. PMID:27572634

Factors Associated With Intestinal Constipation in Chronic Patients With Stroke Sequelae Undergoing Rehabilitation.

PubMed

Engler, Tânia Mara Nascimento de Miranda; Aguiar, Márcia Helena de Assis; Furtado, Íris Aline Brito; Ribeiro, Samile Pereira; de Oliveira, Pérola; Mello, Paulo Andrade; Padula, Marcele Pescuma Capeletti; Beraldo, Paulo Sérgio Siebra

The objective of this study was to define which stroke-related factors constitute independent variables in the incidence of intestinal constipation (IC) of chronic patients admitted to a hospital rehabilitation program. All patients consecutively admitted for rehabilitation were recruited for the study. In the Poisson multiple regression analysis using a hierarchical model, sociodemographic variables, comorbidities, medication, previous history of constipation, life habits, and stroke-related variables were considered for defining factors associated with IC. A 31% prevalence (95% confidence interval [CI]: 25.3-37.1) of IC was detected. Among the factors associated, female gender (adjusted prevalence ratio [PRadjusted] = 1.79; 95% CI: 1.20-2.68), intestinal complaints prior to stroke (PRadjusted = 3.71; 95% CI: 2.60-5.31), intake of less than 800 ml of fluid per day (PRadjusted = 1.72; 95% CI: 1.20- 2.45), age greater than 65 years at brain injury (PRadjusted = 1.67; 95% CI: 1.01-2.75), and partially impaired anterior brain circulation (PRadjusted = 3.35; 95% CI: 1.02-10.97) were associated with IC. Female gender, elderly, prior history of IC, low fluid intake, and partial impairment of anterior brain circulation were factors independently associated with IC in stroke survivors undergoing rehabilitation. These findings require further validation and may serve toward improving bowel retraining programs for this patient group.

Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

PubMed

Katz, Laura; Tripp, Dean A; Carr, Lesley K; Mayer, Robert; Moldwin, Robert M; Nickel, J Curtis

2017-08-01

To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The Mr 140,000 Intermediate Chain of Chlamydomonas Flagellar Inner Arm Dynein Is a WD-Repeat Protein Implicated in Dynein Arm Anchoring

PubMed Central

Yang, Pinfen; Sale, Winfield S.

1998-01-01

Previous structural and biochemical studies have revealed that the inner arm dynein I1 is targeted and anchored to a unique site located proximal to the first radial spoke in each 96-nm axoneme repeat on flagellar doublet microtubules. To determine whether intermediate chains mediate the positioning and docking of dynein complexes, we cloned and characterized the 140-kDa intermediate chain (IC140) of the I1 complex. Sequence and secondary structural analysis, with particular emphasis on β-sheet organization, predicted that IC140 contains seven WD repeats. Reexamination of other members of the dynein intermediate chain family of WD proteins indicated that these polypeptides also bear seven WD/β-sheet repeats arranged in the same pattern along each intermediate chain protein. A polyclonal antibody was raised against a 53-kDa fusion protein derived from the C-terminal third of IC140. The antibody is highly specific for IC140 and does not bind to other dynein intermediate chains or proteins in Chlamydomonas flagella. Immunofluorescent microscopy of Chlamydomonas cells confirmed that IC140 is distributed along the length of both flagellar axonemes. In vitro reconstitution experiments demonstrated that the 53-kDa C-terminal fusion protein binds specifically to axonemes lacking the I1 complex. Chemical cross-linking indicated that IC140 is closely associated with a second intermediate chain in the I1 complex. These data suggest that IC140 contains domains responsible for the assembly and docking of the I1 complex to the doublet microtubule cargo. PMID:9843573

[Impact of frailty over the functional state of hospitalized elderly].

PubMed

García-Cruz, Juan Carlos; García-Peña, Carmen

2016-01-01

Frailty in elderly results from impaired physiological reserve in multiple systems. Establishing if frail elderly inpatients develop more functional impairment at discharge, will allow the development of strategies for preventing or limiting the deterioration in this vulnerable group. Prospective cohort in 133 elderly inpatients. At admission, frailty, functional status, comorbidity and comprehensive geriatric evaluation were determined. The main outcome was functional state at hospital discharge. 64 patients presented frailty (48.1%) and 69 did not present that state (51.9%), with a mean age of 73 and 68 years, respectively. Mean decrement in functional state at discharge was -8.06 % (IC 95 % -10.38 to -5.74), from 97.97 % to 89.91 % (p < 0.001) in patients who did not present frailty, and -21.18 % (IC 95 % -24.97 to -17.38), from 87.52 % to 66.34 % (p < 0.001) in frail patients. The difference between groups at discharge was -14.37 % (IC 95 % -16.80 to -11.94, p < 0.001) to the detriment of the frail. Frailty was associated with functional impairment in the univariated and multivariated analysis, beta -13.11 % (IC 95 % -17.45 to -8.78, p < 0.001) and beta -17.27 (IC 95 % -23.27 to -11.28, p < 0.001), respectively. In the final model, frailty (beta -14.73, IC 95 % -19.39 to -10.07, p < 0.001) and cognitive impairment (beta -8.19, IC 95 % -15.28 to -1.10, p = 0.024) predict functional decrement. Frailty independently predicts functional impairment at hospital discharge.

Performance comparison of machine learning algorithms and number of independent components used in fMRI decoding of belief vs. disbelief.

PubMed

Douglas, P K; Harris, Sam; Yuille, Alan; Cohen, Mark S

2011-05-15

Machine learning (ML) has become a popular tool for mining functional neuroimaging data, and there are now hopes of performing such analyses efficiently in real-time. Towards this goal, we compared accuracy of six different ML algorithms applied to neuroimaging data of persons engaged in a bivariate task, asserting their belief or disbelief of a variety of propositional statements. We performed unsupervised dimension reduction and automated feature extraction using independent component (IC) analysis and extracted IC time courses. Optimization of classification hyperparameters across each classifier occurred prior to assessment. Maximum accuracy was achieved at 92% for Random Forest, followed by 91% for AdaBoost, 89% for Naïve Bayes, 87% for a J48 decision tree, 86% for K*, and 84% for support vector machine. For real-time decoding applications, finding a parsimonious subset of diagnostic ICs might be useful. We used a forward search technique to sequentially add ranked ICs to the feature subspace. For the current data set, we determined that approximately six ICs represented a meaningful basis set for classification. We then projected these six IC spatial maps forward onto a later scanning session within subject. We then applied the optimized ML algorithms to these new data instances, and found that classification accuracy results were reproducible. Additionally, we compared our classification method to our previously published general linear model results on this same data set. The highest ranked IC spatial maps show similarity to brain regions associated with contrasts for belief > disbelief, and disbelief < belief. Copyright © 2010 Elsevier Inc. All rights reserved.

HPLC-DAD fingerprinting analysis, antioxidant activities of Tithonia diversifolia (Hemsl.) A. Gray leaves and its inhibition of key enzymes linked to Alzheimer's disease.

PubMed

Ojo, Oluwafemi Adeleke; Ojo, Adebola Busola; Ajiboye, Basiru Olaitan; Olaiya, Oluranti; Okesola, Mary Abiola; Boligon, Aline Augusti; de Campos, Marli Matiko Anraku; Oyinloye, Babatunji Emmanuel; Kappo, Abidemi Paul

2018-01-01

Tithonia diversifolia (Hemsl.) A. Gray leaves have long been used to manage neurodegenerative diseases without scientific basis. This study characterized the phenolic constituents, evaluated the antioxidant properties of phenolic extracts from T. diversifolia leaves used as traditional medicine in Africa and its inhibition of key enzymes linked to Alzheimer's disease. The extract was rich in phenolic acids (gallic acid, chlorogenic acid, caffeic acid and p -coumaric acid) and flavonoids (apigenin) and had 1,1-diphenyl-2-picryl-hydrazil radical scavenging abilities (IC 50  = 41.05 μg. mL -1 ), 2,2-Azino-bis3-ethylbenthiazoline-6sulphonic acid radical scavenging ability (IC 50  = 33.51 μg. mL -1 ), iron chelation (IC 50  = 38.50 μg. mL -1 ), reducing power (Fe 3+ - Fe 2+ ) (7.34 AAEmg/100 g), inhibited acetylcholinesterase (IC 50  = 39.27 μg mL -1 ) and butyrylcholinesterase (IC 50  = 35.01 μg mL -1 ) activities. These results reveal the leaf as a rich source of phenolic compounds with antioxidant and cholinesterase inhibitory activity.

Quantitative Spectroscopy of Supergiants in the Local Group Dwarf Galaxy IC 1613: Metallicity and Distance

NASA Astrophysics Data System (ADS)

Berger, Travis A.; Kudritzki, Rolf-Peter; Urbaneja, Miguel A.; Bresolin, Fabio; Gieren, Wolfgang; Pietrzyński, Grzegorz; Przybilla, Norbert

2018-06-01

We present a spectral analysis of 21 blue supergiant stars of spectral types late B to early A within the Local Group dwarf galaxy IC 1613, based on VLT Focal Reducer and Low Dispersion Spectrograph 2 low-resolution spectra. Combining our results with studies of early B-type blue supergiants, we report a wide bimodal distribution of metallicities with two peaks around [Z] ∼ ‑0.50 dex and [Z] ∼ ‑0.85 dex. The bimodal distribution correlates with spatial location, when compared with column densities of neutral hydrogen in IC 1613. While the low [Z] objects appear in regions of relatively high ISM H I column densities or close to them, the high [Z] supergiants are found in the central H I hole that is almost devoid of hydrogen. This suggests there are varied chemical evolution histories for the young stellar populations in IC 1613. Utilizing the flux-weighted gravity–luminosity relation, we determine IC 1613's distance modulus as m ‑ M = 24.39 ± 0.11 mag. This value is in agreement within previous distance measurements using the near-infrared period–luminosity relationship of Cepheids and the tip of the red giant branch.

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

Horesh, Assaf; Kulkarni, Shrinivas R.; Corsi, Alessandra

Only a few cases of Type Ic supernovae (SNe) with high-velocity ejecta (≥0.2 c) have been discovered and studied. Here, we present our analysis of radio and X-ray observations of the Type Ic SN PTF 12gzk. The radio emission declined less than 10 days after explosion, suggesting SN ejecta expanding at high velocity (∼0.3 c). The radio data also indicate that the density of the circumstellar material (CSM) around the supernova is lower by a factor of ∼10 than the CSM around normal Type Ic SNe. PTF 12gzk may therefore be an intermediate event between a 'normal' SN Ic andmore » a gamma-ray-burst-SN-like event. Our observations of this rapidly declining radio SN at a distance of 58 Mpc demonstrates the potential to detect many additional radio SNe, given the new capabilities of the Very Large Array (improved sensitivity and dynamic scheduling), which are currently missed, leading to a biased view of radio SNe Ic. Early optical discovery followed by rapid radio observations would provide a full description of the ejecta velocity distribution and CSM densities around stripped massive star explosions as well as strong clues about the nature of their progenitor stars.« less

Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays

PubMed Central

Staats, Janet S.; Enzor, Jennifer H.; Sanchez, Ana M.; Rountree, Wes; Chan, Cliburn; Jaimes, Maria; Chan, Ray Chun-Fai; Gaur, Amitabh; Denny, Thomas N.; Weinhold, Kent J.

2014-01-01

The External Quality Assurance Program Oversight Laboratory (EQAPOL) Flow Cytometry Program assesses the proficiency of NIH/NIAID/DAIDS-supported and potentially other interested research laboratories in performing Intracellular Cytokine Staining (ICS) assays. The goal of the EQAPOL Flow Cytometry External Quality Assurance Program (EQAP) is to provide proficiency testing and remediation for participating sites. The program is not punitive; rather, EQAPOL aims to help sites identify areas for improvement. EQAPOL utilizes a highly standardized ICS assay to minimize variability and readily identify those sites experiencing technical difficulties with their assays. Here, we report the results of External Proficiency 3 (EP3) where participating sites performed a 7-color ICS assay. On average, sites perform well in the Flow Cytometry EQAP (median score is “Good”). The most common technical issues identified by the program involve protocol adherence and data analysis; these areas have been the focus of site remediation. The EQAPOL Flow Cytometry team is now in the process of expanding the program to 8-color ICS assays. Evaluating polyfunctional ICS responses would align the program with assays currently being performed in support of HIV immune monitoring assays. PMID:24968072

What works in implementation of integrated care programs for older adults with complex needs? A realist review

PubMed Central

Kirst, Maritt; Im, Jennifer; Burns, Tim; Baker, G. Ross; Goldhar, Jodeme; O'Campo, Patricia; Wojtak, Anne; Wodchis, Walter P

2017-01-01

Abstract Purpose A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience. Data sources International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies. Study selection Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English. Data extraction Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes. Results of data synthesis A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs. Conclusions This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators. PMID:28992156

Ileal conduit vs orthotopic neobladder: Which one offers the best health-related quality of life in patients undergoing radical cystectomy? A systematic review of literature and meta-analysis.

PubMed

Ziouziou, I; Irani, J; Wei, J T; Karmouni, T; El Khader, K; Koutani, A; Iben Attya Andaloussi, A

2018-04-01

Orthotopic neobladder (ONB) and ileal conduit (IC) are the most commonly practiced techniques of urinary diversion (UD) after radical cystectomy (RC) in bladder cancer patients. Data in the literature is still discordant regarding which UD technique offers the best HR-QoL. The objective was to compare HR-QoL in patients undergoing ONB and IC after RC, through a systematic review of the literature and meta-analysis. We performed a literature search of PubMed, ScienceDirect, CochraneLibrary and ClinicalTrials.Gov in September 2017 according to the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. The studies were evaluated according to the "Oxford Center for Evidence-Based Medicine" criteria. The outcome measures evaluated were subdomains' scores of Bladder Cancer Index BCI: urinary function (UF), urinary bother (UB), bowel function (BF), bowel bother (BB), sexual function (SF) and sexual bother (SB). Continuous outcomes were compared using weighted means differences, with 95% confidence intervals. The presence of publication bias was examined by funnel plots. Four studies met the inclusion criteria. The pooled results demonstrated better UF and UB scores in IC patients: differences were -18.17 (95% CI: -27.49, -8.84, P=0.0001) and -3.72 (95% CI: -6.66, -0.79, P=0.01) respectively. There was no significant difference between IC and ONB patients in terms of BF and BB. SF was significantly better in ONB patients: the difference was 12.7 (95% CI, 6.32, 19.08, P<0.0001). However no significant difference was observed regarding SB. This meta-analysis of non-randomized studies demonstrated a better HR-QoL in urinary outcomes in IC patients compared with ONB patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Investigating the effect of emetic compounds on chemotaxis in Dictyostelium identifies a non-sentient model for bitter and hot tastant research.

PubMed

Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L R; Williams, Robin S B

2011-01-01

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds--denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers--capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC(50) = 11.9 ± 4.0 µM) > quinine hydrochloride (IC(50) = 44.3 ± 6.8 µM) > denatonium benzoate (IC(50) = 129 ± 4 µM) > phenylthiourea (IC(50) = 366 ± 5 µM) > copper sulphate (IC(50) = 1433 ± 3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general.

Identification of homemade inorganic explosives by ion chromatographic analysis of post-blast residues.

PubMed

Johns, Cameron; Shellie, Robert A; Potter, Oscar G; O'Reilly, John W; Hutchinson, Joseph P; Guijt, Rosanne M; Breadmore, Michael C; Hilder, Emily F; Dicinoski, Greg W; Haddad, Paul R

2008-02-29

Anions and cations of interest for the post-blast identification of homemade inorganic explosives were separated and detected by ion chromatographic (IC) methods. The ionic analytes used for identification of explosives in this study comprised 18 anions (acetate, benzoate, bromate, carbonate, chlorate, chloride, chlorite, chromate, cyanate, fluoride, formate, nitrate, nitrite, perchlorate, phosphate, sulfate, thiocyanate and thiosulfate) and 12 cations (ammonium, barium(II), calcium(II), chromium(III), ethylammonium, magnesium(II), manganese(II), methylammonium, potassium(I), sodium(I), strontium(II), and zinc(II)). Two IC separations are presented, using suppressed IC on a Dionex AS20 column with potassium hydroxide as eluent for anions, and non-suppressed IC for cations using a Dionex SCS 1 column with oxalic acid/acetonitrile as eluent. Conductivity detection was used in both cases. Detection limits for anions were in the range 2-27.4ppb, and for cations were in the range 13-115ppb. These methods allowed the explosive residue ions to be identified and separated from background ions likely to be present in the environment. Linearity (over a calibration range of 0.05-50ppm) was evaluated for both methods, with r(2) values ranging from 0.9889 to 1.000. Reproducibility over 10 consecutive injections of a 5ppm standard ranged from 0.01 to 0.22% relative standard deviation (RSD) for retention time and 0.29 to 2.16%RSD for peak area. The anion and cation separations were performed simultaneously by using two Dionex ICS-2000 chromatographs served by a single autoinjector. The efficacy of the developed methods was demonstrated by analysis of residue samples taken from witness plates and soils collected following the controlled detonation of a series of different inorganic homemade explosives. The results obtained were also confirmed by parallel analysis of the same samples by capillary electrophoresis (CE) with excellent agreement being obtained.

Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies

PubMed Central

Kühl, Susanne J.; Toberer, Matthias; Keis, Oliver; Tolks, Daniel; Fischer, Martin R.; Kühl, Michael

2017-01-01

Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC) method can address this deficiency. The goal of this study was: to analyse the motivation and satisfaction of the students in a biochemistry seminar through the use of the e-learning-based IC method, to investigate the acceptance against the IC teaching method in biochemistry, and to compare the learning success achieved using the IC approach with that of a traditional course. We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee “New Media” [30] in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students), but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the acquisition of knowledge by MC exams. Results: On a Likert scale from 1 (strongly disagree) to 6 (strongly agree), the students in the IC intervention groups could be seen to be much more motivated (5.53) than students in the control group (4.01). Students in the IC intervention groups also recognised the relevance of the learning content much more clearly (5.44) than students in the control group (4.01). Furthermore, the IC group also observed that additional competencies were trained in addition to the biochemistry content. In addition, the IC intervention group award the event a school grade of 1.53, the traditional control group a grade of 2.96. The teaching videos were rated very positively by both groups with an average school grade of 1.3 in each case. A qualitative analysis showed that the motivation and a positive attitude of the lecturers played a decisive role in the successful implementation of the IC method. Discussion and conclusion: Pre-clinical students display a high acceptance of the e-learning-based IC method. Teaching communication competencies in a biochemistry seminar was also rated very positively by the students. The quality of the teaching video and the motivation of the lecturers were shown to be a critical parameter for the successful performance of the IC method. What’s more, the IC method can contribute to implementing a competence orientation in medical studies. PMID:28890922

Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies.

PubMed

Kühl, Susanne J; Toberer, Matthias; Keis, Oliver; Tolks, Daniel; Fischer, Martin R; Kühl, Michael

2017-01-01

Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC) method can address this deficiency. The goal of this study was: to analyse the motivation and satisfaction of the students in a biochemistry seminar through the use of the e-learning-based IC method, to investigate the acceptance against the IC teaching method in biochemistry, and to compare the learning success achieved using the IC approach with that of a traditional course. We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee "New Media" [30] in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students), but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the acquisition of knowledge by MC exams. Results: On a Likert scale from 1 (strongly disagree) to 6 (strongly agree), the students in the IC intervention groups could be seen to be much more motivated (5.53) than students in the control group (4.01). Students in the IC intervention groups also recognised the relevance of the learning content much more clearly (5.44) than students in the control group (4.01). Furthermore, the IC group also observed that additional competencies were trained in addition to the biochemistry content. In addition, the IC intervention group award the event a school grade of 1.53, the traditional control group a grade of 2.96. The teaching videos were rated very positively by both groups with an average school grade of 1.3 in each case. A qualitative analysis showed that the motivation and a positive attitude of the lecturers played a decisive role in the successful implementation of the IC method. Discussion and conclusion: Pre-clinical students display a high acceptance of the e-learning-based IC method. Teaching communication competencies in a biochemistry seminar was also rated very positively by the students. The quality of the teaching video and the motivation of the lecturers were shown to be a critical parameter for the successful performance of the IC method. What's more, the IC method can contribute to implementing a competence orientation in medical studies.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

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

Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu; Melotek, James M.; Blair, Elizabeth A.

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-freemore » survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.« less

An 1H NMR-based metabolomic approach to compare the chemical profiling of retail samples of ground roasted and instant coffees.

PubMed

Villalón-López, Nayelli; Serrano-Contreras, José I; Téllez-Medina, Darío I; Gerardo Zepeda, L

2018-04-01

The present non-targeted 1 H NMR-based fingerprinting approach along with multivariate analysis established differences between representative aqueous extracts of commercial ground roasted coffee (GRC) and instant (soluble) coffee (IC) samples. The latter were prepared either by spray drying or freeze drying. When comparing a total of 33 compounds between GRC and IC, the latter product contained a remarkable increase in 5-(hydroxymethyl)furfural and carbohydrates, as well as a clear decrease in trigonelline, N-methylpyridinium, caffeine, caffeoylquinic acids and 2-furylmethanol. Furthermore, the current protocol was able to detect the subtle chemical differences between spray-dried and freeze-dried IC. The aforementioned metabolites could serve as target molecules in the attempt to preserve, as much as possible, the organoleptic and nutraceutical properties of GRC during the industrial drying processes used in the production of the two commercial types of IC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Boosting specificity of MEG artifact removal by weighted support vector machine.

PubMed

Duan, Fang; Phothisonothai, Montri; Kikuchi, Mitsuru; Yoshimura, Yuko; Minabe, Yoshio; Watanabe, Kastumi; Aihara, Kazuyuki

2013-01-01

An automatic artifact removal method of magnetoencephalogram (MEG) was presented in this paper. The method proposed is based on independent components analysis (ICA) and support vector machine (SVM). However, different from the previous studies, in this paper we consider two factors which would influence the performance. First, the imbalance factor of independent components (ICs) of MEG is handled by weighted SVM. Second, instead of simply setting a fixed weight to each class, a re-weighting scheme is used for the preservation of useful MEG ICs. Experimental results on manually marked MEG dataset showed that the method proposed could correctly distinguish the artifacts from the MEG ICs. Meanwhile, 99.72% ± 0.67 of MEG ICs were preserved. The classification accuracy was 97.91% ± 1.39. In addition, it was found that this method was not sensitive to individual differences. The cross validation (leave-one-subject-out) results showed an averaged accuracy of 97.41% ± 2.14.

The Incident Command System: a literature review.

PubMed

Jensen, Jessica; Thompson, Steven

2016-01-01

Given the foundational and the fundamental role that the Incident Command System (ICS) is intended to play in on-scene response efforts across the United States, it is important to determine what is known about the system and how this is known. Accordingly, this study addresses the following research question: 'How has research explored the ICS?'. To probe this question, a methodological review of the scant, but widening, pool of research literature directly related to the ICS was conducted. This paper reports on the findings of the analysis related to the focus, theoretical frameworks, population and sampling, methods, results, and conclusions of the existing research literature. While undertaken using different methodological approaches, the ICS research suggests that the system may be limited in its usefulness. In addition, the paper discusses the implications of the research for the state of knowledge of the system and for the direction of future research. © 2016 The Author(s). Disasters © Overseas Development Institute, 2016.

[Chemical constituents of Jasminum giraldii and their antioxidant activity].

PubMed

Zhang, Xiu-Peng; Qin, Hui; Yang, Fang; Chai, Jiang; Wang, Xin; Song, Xiao-Mei; Mei, Qi-Bing; Feng, Feng; Yue, Zheng-Gang

2014-06-01

Ten compounds were isolated from the barks of Jasminum giraldii by means of various of chromatographic techniques such as silica gel, Sephadex LH-20 and Rp-HPLC. Their structures were identified by spectroscopic data analysis as (+)-medioresinol (1), (+) -syringaresinol (2), syringaresinol-4'-O-beta-D-glucopyranoside (3), oleanic acid (4), 3-methoxy-4-hydroxy-trans-cinnamaldehyde (5), trans-sinapaldehyde (6), syringaldehyde (7), 1-(4-methoxy -phenyl) -ethanol (8), trans-cinnamic acid (9), and 4-(1-methoxyethyl) -phenol (10). Among them, compounds 1-3, 5-8 and 10 were isolated from the J. genus for the first time and compounds 4 and 9 were obtained from J. giraldii for the first time. In the DPPH free radical scavenging assay, compound 1 exhibited significant activity (IC50 55.1 micromol x L(-1)), compared with vitamin C(IC50 59.9 micromol x L(-1)); and compound 2 showed moderate activity (IC50 79.0 micromol x L(-1)), compared with 2, 6-di-tert-butyl4-methylphenol (IC50 236 micromol x L(-1)).

["Hope Dies Last …" - Cross-Sectoral Cooperation in Integrated Care].

PubMed

Ruppert, Daniel; Stegbauer, Constanze; Bramesfeld, Anke; Bestmann, Beate; Szecsenyi, Joachim; Götz, Katja

2017-04-01

Objective Multiple models of Integrated Care (IC) have been implemented in German mental health services in the last decade in order to improve cross-sectoral, interdisciplinary cooperation. This study investigates an IC network model providing home treatment, case management and a 24/7 hotline. The aim of the study was to explore how health professionals working in this service model perceive both cooperation within their facilities and with external stakeholders. Methods 5 focus groups with 39 health professionals working in an IC mental health network were conducted and analyzed with qualitative content analysis. Results Focus groups participants reported on excellent cooperation within their facilities. The cooperation with external stakeholders, i. e. physicians, psychotherapists and psychiatric clinics, leaves room for improvement. Conclusions Until now little consideration has been given to the perspectives of health professionals. Cooperation within IC mental health networks seems to be effective. Cooperation with stakeholders outside the networks needs to be enhanced. © Georg Thieme Verlag KG Stuttgart · New York.

Mechanism of strength degradation for hot corrosion of alpha-SiC

NASA Technical Reports Server (NTRS)

Smialek, J. L.; Jacobson, N. S.

1984-01-01

Sintered alpha SiC was corroded by thin films of Na2SO4 and Na2CO3 molten salts at 1000%. This hot corrosion attack reduced room temperature strengths by as much as 50%. Strength degradation was porportional to the degree and uniformity of corrosion pitting attack as controlled by the chemistry of the molten salt. Extensive fractography identified corrosion pits as the most prevalent source of failure. A fracture mechanics treatment of the strength/pit depth relationship produced an average K sub IC equal to 2.6 MPa sub m 1/2, which is consistent with published values.

Mechanism of strength degradation for hot corrosion of alpha-SiC

NASA Technical Reports Server (NTRS)

Smialek, James L.; Jacobson, Nathan S.

1986-01-01

Sintered alpha SiC was corroded by thin films of Na2SO4 and Na2CO3 molten salts at 1000 percent. This hot corrosion attack reduced room temperature strengths by as much as 50 percent. Strength degradation was proportional to the degree and uniformity of corrosion pitting attack as controlled by the chemistry of the molten salt. Extensive fractography identified corrosion pits as the most prevalent source of failure. A fracture mechanics treatment of the strength/pit depth relationship produced an average K sub IC equal to 2.6 MPa sub m 1/2, which is cnsistent ith published values.

Analysis of acidic components, heavy metals and PAHS of particulate in the Changwon-Masan area of Korea.

PubMed

Lee, Byeong-Kyu; Lee, Chang-Heub

2008-01-01

This study is an analysis of the concentrations and components of heavy metals in PM2.5 and the total suspended particulate (TSP) collected at a mechanical industrial complex (IC) site in Changwon and at a residential site in Masan, Korea. Particulate was collected during two sampling periods, from the late summer to the early fall and from the middle to late fall, at the IC site and one sampling period, from the middle fall to the early winter, at the residential site. PM2.5 and TSP samples were taken by an annular denuder system and a hi-volume air sampler, respectively. The authors also identified the concentrations and components of heavy metals extracted from the PM2.5 and TSP filters, the acidic components extracted from the PM2.5 filters, and the polycyclic aromatic hydrocarbons (PAHs) extracted from polyurethane foam (PUF) plug. The average concentrations of the PM2.5 collected at the IC and residential sites were very similar. Major sources of PM2.5 at the study sites, however, were air emissions from vehicles and industry as well as emissions from residential heating and soil origins, respectively. The higher concentrations of the TSP at the IC site, as compared to those at the residential site, were due to either increased suspended dust from vehicle emissions or re-suspended road dust because of increased vehicle speeds near the IC site. Heavy metal concentrations in the TSPs were higher than those in the PM2.5. The heavy metal concentrations in the PM2.5 and TSP at the IC site with heavy traffic were substantially greater than those at the residential site. The concentrations of TSP and heavy metals and PAHs in PM during the period of the middle to late fall was much higher than those during the period of the late summer to early fall at the IC site. This is because of the difference in meteorological characteristics and energy uses between two periods. The residential site also showed higher concentrations of acidic anions while the IC site showed higher concentrations of acidic cation. Secondary aerosols or particulates, such as ammonium nitrate or ammonium nitrite, might have been important constituents of the PM2.5 at the residential site. The PAHs in the TSP collected at the IC site was greatly affected by traffic and industry emissions consisting mostly of high molecular weight PAHs with two to four rings. PAHs in the TSP at the site, however, were affected by residential heating and air emissions from small chemical plants having higher concentrations of low molecular weight PAHs with five to six rings.

V&V Plan for FPGA-based ESF-CCS Using System Engineering Approach.

NASA Astrophysics Data System (ADS)

Maerani, Restu; Mayaka, Joyce; El Akrat, Mohamed; Cheon, Jung Jae

2018-02-01

Instrumentation and Control (I&C) systems play an important role in maintaining the safety of Nuclear Power Plant (NPP) operation. However, most current I&C safety systems are based on Programmable Logic Controller (PLC) hardware, which is difficult to verify and validate, and is susceptible to software common cause failure. Therefore, a plan for the replacement of the PLC-based safety systems, such as the Engineered Safety Feature - Component Control System (ESF-CCS), with Field Programmable Gate Arrays (FPGA) is needed. By using a systems engineering approach, which ensures traceability in every phase of the life cycle, from system requirements, design implementation to verification and validation, the system development is guaranteed to be in line with the regulatory requirements. The Verification process will ensure that the customer and stakeholder’s needs are satisfied in a high quality, trustworthy, cost efficient and schedule compliant manner throughout a system’s entire life cycle. The benefit of the V&V plan is to ensure that the FPGA based ESF-CCS is correctly built, and to ensure that the measurement of performance indicators has positive feedback that “do we do the right thing” during the re-engineering process of the FPGA based ESF-CCS.

Microwave evaluation of electromigration susceptibility in advanced interconnects.

PubMed

Sunday, Christopher E; Veksler, Dmitry; Cheung, Kin C; Obeng, Yaw S

2017-11-07

Traditional metrology has been unable to adequately address the needs of the emerging integrated circuits (ICs) at the nano scale; thus, new metrology and techniques are needed. For example, the reliability challenges in fabrication need to be well understood and controlled to facilitate mass production of through-substrate-via (TSV) enabled three-dimensional integrated circuits (3D-ICs). This requires new approaches to the metrology. In this paper, we use the microwave propagation characteristics to study the reliability issues that precede the physical damage caused by electromigration in the Cu-filled TSVs. The pre-failure microwave insertion losses and group delay are dependent on both the device temperature and the amount of current forced through the devices-under-test. The microwave insertion losses increase with the increase in the test temperature, while the group delay increases with the increase in the forced direct current magnitude. The microwave insertion losses are attributed to the defect mobility at the Cu-TiN interface, and the group delay changes are due to resistive heating in the interconnects, which perturbs the dielectric properties of the cladding dielectrics of the copper fill in the TSVs. https://doi.org/10.1063/1.4992135.

Operando lithium plating quantification and early detection of a commercial LiFePO4 cell cycled under dynamic driving schedule

NASA Astrophysics Data System (ADS)

Anseán, D.; Dubarry, M.; Devie, A.; Liaw, B. Y.; García, V. M.; Viera, J. C.; González, M.

2017-07-01

Lithium plating is considered one of the most detrimental phenomenon in lithium ion batteries (LIBs), as it increases cell degradation and might lead to safety issues. Plating induced LIB failure presents a major concern for emerging applications in transportation and electrical energy storage. Hence, the necessity to operando monitor, detect and analyze lithium plating becomes critical for safe and reliable usage of LIB systems. Here, we report in situ lithium plating analyses for a commercial graphite||LiFePO4 cell cycled under dynamic stress test (DST) driving schedule. We designed a framework based on incremental capacity (IC) analysis and mechanistic model simulations to quantify degradation modes, relate their effects to lithium plating occurrence and assess cell degradation. The results show that lithium plating was induced by large loss of active material on the negative electrode that eventually led the electrode to over-lithiate. Moreover, when lithium plating emerged, we quantified that the loss of lithium inventory pace was increased by a factor of four. This study illustrates the benefits of the proposed framework to improve lithium plating analysis. It also discloses the symptoms of lithium plating formation, which prove valuable for novel, online strategies on early lithium plating detection.

Music video shot segmentation using independent component analysis and keyframe extraction based on image complexity

NASA Astrophysics Data System (ADS)

Li, Wei; Chen, Ting; Zhang, Wenjun; Shi, Yunyu; Li, Jun

2012-04-01

In recent years, Music video data is increasing at an astonishing speed. Shot segmentation and keyframe extraction constitute a fundamental unit in organizing, indexing, retrieving video content. In this paper a unified framework is proposed to detect the shot boundaries and extract the keyframe of a shot. Music video is first segmented to shots by illumination-invariant chromaticity histogram in independent component (IC) analysis feature space .Then we presents a new metric, image complexity, to extract keyframe in a shot which is computed by ICs. Experimental results show the framework is effective and has a good performance.

A first application of independent component analysis to extracting structure from stock returns.

PubMed

Back, A D; Weigend, A S

1997-08-01

This paper explores the application of a signal processing technique known as independent component analysis (ICA) or blind source separation to multivariate financial time series such as a portfolio of stocks. The key idea of ICA is to linearly map the observed multivariate time series into a new space of statistically independent components (ICs). We apply ICA to three years of daily returns of the 28 largest Japanese stocks and compare the results with those obtained using principal component analysis. The results indicate that the estimated ICs fall into two categories, (i) infrequent large shocks (responsible for the major changes in the stock prices), and (ii) frequent smaller fluctuations (contributing little to the overall level of the stocks). We show that the overall stock price can be reconstructed surprisingly well by using a small number of thresholded weighted ICs. In contrast, when using shocks derived from principal components instead of independent components, the reconstructed price is less similar to the original one. ICA is shown to be a potentially powerful method of analyzing and understanding driving mechanisms in financial time series. The application to portfolio optimization is described in Chin and Weigend (1998).

Noise reduction in functional near-infrared spectroscopy signals by independent component analysis

NASA Astrophysics Data System (ADS)

Santosa, Hendrik; Jiyoun Hong, Melissa; Kim, Sung-Phil; Hong, Keum-Shik

2013-07-01

Functional near-infrared spectroscopy (fNIRS) is used to detect concentration changes of oxy-hemoglobin and deoxy-hemoglobin in the human brain. The main difficulty entailed in the analysis of fNIRS signals is the fact that the hemodynamic response to a specific neuronal activation is contaminated by physiological and instrument noises, motion artifacts, and other interferences. This paper proposes independent component analysis (ICA) as a means of identifying the original hemodynamic response in the presence of noises. The original hemodynamic response was reconstructed using the primary independent component (IC) and other, less-weighting-coefficient ICs. In order to generate experimental brain stimuli, arithmetic tasks were administered to eight volunteer subjects. The t-value of the reconstructed hemodynamic response was improved by using the ICs found in the measured data. The best t-value out of 16 low-pass-filtered signals was 37, and that of the reconstructed one was 51. Also, the average t-value of the eight subjects' reconstructed signals was 40, whereas that of all of their low-pass-filtered signals was only 20. Overall, the results showed the applicability of the ICA-based method to noise-contamination reduction in brain mapping.

Post-test analysis of PIPER-ONE PO-IC-2 experiment by RELAP5/MOD3 codes

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

Bovalini, R.; D`Auria, F.; Galassi, G.M.

1996-11-01

RELAP5/MOD3.1 was applied to the PO-IC-2 experiment performed in PIPER-ONE facility, which has been modified to reproduce typical isolation condenser thermal-hydraulic conditions. RELAP5 is a well known code widely used at the University of Pisa during the past seven years. RELAP5/MOD3.1 was the latest version of the code made available by the Idaho National Engineering Laboratory at the time of the reported study. PIPER-ONE is an experimental facility simulating a General Electric BWR-6 with volume and height scaling ratios of 1/2,200 and 1./1, respectively. In the frame of the present activity a once-through heat exchanger immersed in a pool ofmore » ambient temperature water, installed approximately 10 m above the core, was utilized to reproduce qualitatively the phenomenologies expected for the Isolation Condenser in the simplified BWR (SBWR). The PO-IC-2 experiment is the flood up of the PO-SD-8 and has been designed to solve some of the problems encountered in the analysis of the PO-SD-8 experiment. A very wide analysis is presented hereafter including the use of different code versions.« less

Variable p-CREB expression depicts different asthma phenotypes.

PubMed

Chiappara, G; Chanez, P; Bruno, A; Pace, E; Pompeo, F; Bousquet, J; Bonsignore, G; Gjomarkaj, M

2007-07-01

Chromatin modification may play a role in inflammatory gene regulation in asthma. Cyclic adenosine mono-phosphate response element-binding protein (CREB), with the specific co-activator, the CREB-binding protein (CBP), contributes to the acetylation of chromatin and to the transcription of pro-inflammatory genes. To evaluate the expression of CBP and of phospho-CREB (p-CREB) in bronchial biopsies and in peripheral blood mononuclear cells (PBMC) of controls (C), untreated (UA), inhaled steroid treated (ICS) and steroid-dependent asthmatic (SDA) patients. We used immunohistochemistry in bronchial biopsies and western blot analysis and immunocytochemistry in PBMC. Cyclic adenosine mono-phosphate response element-binding protein expression, in the epithelium was similar in all groups, while p-CREB expression was increased in UA and in SDA in comparison with ICS and C subjects (C vs UA P = 0.002, C vs SDA P = 0.007), (ICS vs SDA P = 0.005), (ICS vs UA P = 0.001). Interestingly, also in the submucosa, p-CREB was increased in UA and SDA in comparison with ICS and C subjects (C vs UA P = 0.0004) (C vs SDA P < 0.0001) (ICS vs UA P = 0.002) (ICS vs SDA P < 0.0001) and positively correlated with leukocyte infiltration within the bronchi (CD45RB+ cells). Similar results were obtained with PBMC isolated from the same patient groups. Incubation of PBMC in vitro, with fluticasone propionate, decreased the p-CREB expression induced by cytokine activation (interferon-gamma, tumor necrosis factor-alpha). This study demonstrates that the expression of p-CREB is related, in asthma, to the persistent inflammation according to the disease severity. p-CREB expression can be modulated by glucocorticoids in responsive patients.

The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus

PubMed Central

Ito, Tetsufumi; Oliver, Douglas L.

2012-01-01

The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB. PMID:22855671

Costs of interstitial cystitis in a managed care population.

PubMed

Clemens, J Quentin; Meenan, Richard T; Rosetti, Maureen C O'Keeffe; Kimes, Terry; Calhoun, Elizabeth A

2008-05-01

To assess the direct medical costs, medication, and procedure use associated with interstitial cystitis (IC) in women in the Kaiser Permanente Northwest (KPNW) managed care population. The KPNW electronic medical record was used to identify women diagnosed with IC (n = 239). Each of these patients was matched with three controls according to age and duration in the health plan. Health plan cost accounting data were used to determine the inpatient, outpatient, and pharmacy costs for 1998 to 2003. An analysis of the prescription medication use and cystoscopic and urodynamic procedures commonly associated with IC was also performed. To evaluate for co-morbidities, an automated risk-adjustment model linked to 28 chronic medical conditions was applied to the administrative data sets from both groups. The mean duration from the date of IC diagnosis to the end of the study period was 36.6 months (range 1.4 to 60). The mean yearly costs were 2.4-fold greater for the patients than for the controls ($7100 versus $2994), and the median yearly costs were 3.8-fold greater ($5000 versus $1304). These cost differences were predominantly due to outpatient and pharmacy expenses. Medication and procedure use were significantly greater for the patients than for the controls. These findings were consistent across risk-adjustment model categories, which suggest that the observed cost differences are IC specific. The direct per-person costs of IC are high, with average yearly costs approximately $4000 greater than for the age-matched controls. This cost differential is an underestimate, because the costs preceding the diagnosis, the use of alternative therapies, indirect costs, and the costs of those with IC that is not diagnosed were not included.

Complication incidence of two implant systems up to six years: a comparison between internal and external connection implants.

PubMed

Chae, Sung-Wook; Kim, Young-Sung; Lee, Yong-Moo; Kim, Won-Kyung; Lee, Young-Kyoo; Kim, Su-Hwan

2015-02-01

This study was conducted to compare the cumulative survival rates (CSRs) and the incidence of postloading complications (PLCs) between a bone-level internal connection system (ICS-BL) and an external connection system (ECS). The medical records of patients treated with either a ICS-BL or ECS between 2007 and 2010 at Asan Medical Center were reviewed. PLCs were divided into two categories: biological and technical. Biological complications included >4 mm of probing pocket depth, thread exposure in radiographs, and soft tissue complications, whereas technical complications included chipping of the veneering material, fracture of the implant, fracture of the crown, loosening or fracture of the abutment or screw, loss of retention, and loss of access hole filling material. CSRs were determined by a life-table analysis and compared using the log-rank chi-square test. The incidence of PLC was compared with the Pearson chi-squared test. A total of 2,651 implants in 1,074 patients (1,167 ICS-BLs in 551 patients and 1,484 ECSs in 523 patients) were analyzed. The average observation periods were 3.4 years for the ICS-BLs and 3.1 years for the ECSs. The six-year CSR of all implants was 96.1% (94.9% for the ICS-BLs and 97.1% for the ECSs, P=0.619). Soft tissue complications were more frequent with the ECSs (P=0.005) and loosening or fracture of the abutment or screw occurred more frequently with the ICS-BLs (P<0.001). Within the limitations of this study, the ICS-BL was more prone to technical complications while the ECS was more vulnerable to biological complications.

Effects of inhaled corticosteroids on airway inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis

PubMed Central

Jen, Rachel; Rennard, Stephen I; Sin, Don D

2012-01-01

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD. Methods: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD) to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1), then a random effects model was used to pool the original data; otherwise, a fixed effects model was used. Results: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n =102 participants) and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval). The five studies used bronchoalveolar lavage fluid (n =309), which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval). ICS on the other hand significantly increased macrophage counts (SMD, 0.68 units, 95% confidence interval) in bronchoalveolar lavage fluid. Conclusion: ICS has important immunomodulatory effects in airways with COPD that may explain its beneficial effect on exacerbations and enhanced risk of pneumonia. PMID:23055709

Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.

PubMed

Foutz, Aaron; Appleby, Brian S; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B; Cohen, Mark L; Caughey, Byron; Safar, Jiri G

2017-01-01

Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases that were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and type 1 or type 2 human prions on diagnostic performance. The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1-2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, whereas genetic prion diseases revealed distinct profiles for each PRNP gene mutation. The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and tau proteins, and together with PRNP gene sequencing the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease-two important considerations for envisioned therapeutic interventions. ANN NEUROL 2017;81:79-92. © 2016 American Neurological Association.

Diagnostic and Prognostic Value of Human Prion Detection in Cerebrospinal Fluid

PubMed Central

Foutz, Aaron; Appleby, Brian S.; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B.; Cohen, Mark L.; Caughey, Byron; Safar, Jiri G.

2016-01-01

Objective Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. Methods We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance. Results The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1–2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, while genetic prion diseases revealed distinct profiles for each PRNP gene mutation. Interpretation The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and Tau proteins and together with PRNP gene sequencing, the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease—two important considerations for envisioned therapeutic interventions. PMID:27893164

Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization.

PubMed

Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

2015-01-01

Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients' understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms "neurogenic bladder intermittent catheter" and "spinal cord injury intermittent catheter." Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients' understanding of their condition.

Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application.

PubMed

Guerra, Luciano Lucas; Faccinetti, Natalia Inés; Trabucchi, Aldana; Rovitto, Bruno David; Sabljic, Adriana Victoria; Poskus, Edgardo; Iacono, Ruben Francisco; Valdez, Silvina Noemí

2016-11-24

The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2 ic ) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2 ic and design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). The main findings can be summarized in the following statements: i) TrxIA-2 ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2 ic /L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2 ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2 ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2 ic was legitimized by inhibition or displacement of [ 35 S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection. E. coli GI724 strain emerged as a handy source of recombinant IA-2 ic , achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.

Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

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

Zaczek, R.; Culp, S.; De Souza, E.B.

1991-05-01

The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain regionmore » with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.« less

Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat.

PubMed

Lasker, George F; Pankey, Edward A; Allain, Alexander V; Dhaliwal, Jasdeep S; Stasch, Johannes-Peter; Murthy, Subramanyam N; Kadowitz, Philip J

2013-03-01

Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs. The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions. Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat. Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated. The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response. These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED. © 2012 International Society for Sexual Medicine.

Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML).

PubMed

Guan, Y; Hogge, D E

2000-12-01

One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard chemotherapeutic regimens.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis.

PubMed

Song, Phil Hyun; Chun, So Young; Chung, Jae-Wook; Kim, Yeon Yong; Lee, Hyo Jung; Lee, Jun Nyung; Ha, Yun-Sok; Yoo, Eun Sang; Kwon, Tae Gyun; Kim, Jeongshik; Kim, Dae Hwan; Kim, Bum Soo

2017-09-01

We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Biogenesis of silver nanoparticles using endophytic fungus Pestalotiopsis microspora and evaluation of their antioxidant and anticancer activities.

PubMed

Netala, Vasudeva Reddy; Bethu, Murali Satyanarayana; Pushpalatha, Bobbu; Baki, Vijaya Bhaskar; Aishwarya, Sani; Rao, J Venkateswara; Tartte, Vijaya

An endophytic fungal strain isolated from the leaves of Gymnema sylvestre was identified as Pestalotiopsis microspora VJ1/VS1 based on nucleotide sequencing of internal transcribed spacer region (ITS 1-5.8S-ITS 2) of 18S rRNA gene (NCBI accession number KX213894). In this study, an efficient and ecofriendly approach has been reported for the synthesis of silver nanoparticles (AgNPs) using aqueous culture filtrate of P. microspora . Ultraviolet-visible analysis confirmed the synthesis of AgNPs by showing characteristic absorption peak at 435 nm. Fourier transform infrared spectroscopy analysis revealed the presence of phenolic compounds and proteins in the fungal filtrate, which are plausibly involved in the biosynthesis and capping of AgNPs. Transmission electron microscopy (TEM) showed that the AgNPs were spherical in shape of 2-10 nm in size. Selected area electron diffraction and X-ray diffraction studies determined the crystalline nature of AgNPs with face-centered cubic (FCC) lattice phase. Dynamic light scattering analysis showed that the biosynthesized AgNPs possess high negative zeta potential value of -35.7 mV. Biosynthesized AgNPs were proved to be potential antioxidants by showing effective radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl and H 2 O 2 radicals with IC 50 values of 76.95±2.96 and 94.95±2.18 µg/mL, respectively. The biosynthesized AgNPs exhibited significant cytotoxic effects against B16F10 (mouse melanoma, IC 50 =26.43±3.41 µg/mL), SKOV3 (human ovarian carcinoma, IC 50 =16.24±2.48 µg/mL), A549 (human lung adenocarcinoma, IC 50 =39.83±3.74 µg/mL), and PC3 (human prostate carcinoma, IC 50 =27.71±2.89 µg/mL) cells. The biosynthesized AgNPs were found to be biocompatible toward normal cells (Chinese hamster ovary cell line, IC 50 =438.53±4.2 µg/mL). Cytological observations on most susceptible SKOV3 cells revealed concentration-dependent apoptotic changes that include cell membrane blebbing, cell shrinkage, pyknotic nuclei, karyorrhexis followed by destructive fragmentation of nuclei. The results together in this study strongly provided a base for the development of potential and versatile biomedical applications of biosynthesized AgNPs in the near future.

Biogenesis of silver nanoparticles using endophytic fungus Pestalotiopsis microspora and evaluation of their antioxidant and anticancer activities

PubMed Central

Netala, Vasudeva Reddy; Bethu, Murali Satyanarayana; Pushpalatha, Bobbu; Baki, Vijaya Bhaskar; Aishwarya, Sani; Rao, J Venkateswara; Tartte, Vijaya

2016-01-01

An endophytic fungal strain isolated from the leaves of Gymnema sylvestre was identified as Pestalotiopsis microspora VJ1/VS1 based on nucleotide sequencing of internal transcribed spacer region (ITS 1-5.8S-ITS 2) of 18S rRNA gene (NCBI accession number KX213894). In this study, an efficient and ecofriendly approach has been reported for the synthesis of silver nanoparticles (AgNPs) using aqueous culture filtrate of P. microspora. Ultraviolet-visible analysis confirmed the synthesis of AgNPs by showing characteristic absorption peak at 435 nm. Fourier transform infrared spectroscopy analysis revealed the presence of phenolic compounds and proteins in the fungal filtrate, which are plausibly involved in the biosynthesis and capping of AgNPs. Transmission electron microscopy (TEM) showed that the AgNPs were spherical in shape of 2–10 nm in size. Selected area electron diffraction and X-ray diffraction studies determined the crystalline nature of AgNPs with face-centered cubic (FCC) lattice phase. Dynamic light scattering analysis showed that the biosynthesized AgNPs possess high negative zeta potential value of −35.7 mV. Biosynthesized AgNPs were proved to be potential antioxidants by showing effective radical scavenging activity against 2,2′-diphenyl-1-picrylhydrazyl and H2O2 radicals with IC50 values of 76.95±2.96 and 94.95±2.18 µg/mL, respectively. The biosynthesized AgNPs exhibited significant cytotoxic effects against B16F10 (mouse melanoma, IC50 =26.43±3.41 µg/mL), SKOV3 (human ovarian carcinoma, IC50 =16.24±2.48 µg/mL), A549 (human lung adenocarcinoma, IC50 =39.83±3.74 µg/mL), and PC3 (human prostate carcinoma, IC50 =27.71±2.89 µg/mL) cells. The biosynthesized AgNPs were found to be biocompatible toward normal cells (Chinese hamster ovary cell line, IC50 =438.53±4.2 µg/mL). Cytological observations on most susceptible SKOV3 cells revealed concentration-dependent apoptotic changes that include cell membrane blebbing, cell shrinkage, pyknotic nuclei, karyorrhexis followed by destructive fragmentation of nuclei. The results together in this study strongly provided a base for the development of potential and versatile biomedical applications of biosynthesized AgNPs in the near future. PMID:27826190

Sweat Sodium, Potassium, and Chloride Concentrations Analyzed Same Day as Collection Versus After 7 Days Storage in a Range of Temperatures.

PubMed

Baker, Lindsay B; Barnes, Kelly A; Sopeña, Bridget C; Nuccio, Ryan P; Reimel, Adam J; Ungaro, Corey T

2018-05-22

The purpose of this study was to determine the effect of storage temperature on sodium ([Na + ]), potassium ([K + ]), and chloride ([Cl - ]) concentrations of sweat samples analyzed 7 days after collection. Using the absorbent patch technique, 845 sweat samples were collected from 39 subjects (32 ± 7 years, 72.9 ± 10.5 kg) during exercise. On the same day as collection (PRESTORAGE), 609 samples were analyzed for [Na + ], [Cl - ], and [K + ] by ion chromatography (IC) and 236 samples were analyzed for [Na + ] using a compact ion-selective electrode (ISE). Samples were stored at one of the four conditions: -20 °C (IC, n = 138; ISE, n = 60), 8 °C (IC, n = 144; ISE, n = 59), 23 °C (IC, n = 159; ISE, n = 59), or alternating between 8 °C and 23 °C (IC, n = 168; ISE, n = 58). After 7 days in storage (POSTSTORAGE), samples were reanalyzed using the same technique as PRESTORAGE. PRESTORAGE sweat electrolyte concentrations were highly related to that of POSTSTORAGE (intraclass correlation coefficient: .945-.989, p < .001). Mean differences (95% confidence intervals) between PRESTORAGE and POSTSTORAGE were statistically, but not practically, significant for most comparisons: IC [Na + ]: -0.5(0.9) to -2.1(0.9) mmol/L; IC [K + ]: -0.1(0.1) to -0.2(0.1) mmol/L; IC [Cl - ]: -0.4(1.4) to -1.3(1.3) mmol/L; ISE [Na + ]: -2.0(1.1) to 1.3(1.1) mmol/L. Based on typical error of measurement results, 95% of the time PRESTORAGE and POSTSTORAGE sweat [Na + ], [K + ], and [Cl - ] by IC analysis fell within ±7-9, ±0.6-0.7, and ±9-13 mmol/L, respectively, while sweat [Na + ] by ISE was ±6 mmol/L. All conditions produced high reliability and acceptable levels of agreement in electrolyte concentrations of sweat samples analyzed on the day of collection versus after 7 days in storage.

The use of long acting β₂-agonists, alone or in combination with inhaled corticosteroids, in chronic obstructive pulmonary disease (COPD): a risk-benefit analysis.

PubMed

Cave, Alison C; Hurst, Martin M

2011-05-01

Chronic obstructive pulmonary disease (COPD) is a slowly progressive, largely non-reversible pulmonary disease which is characterised by airflow limitation. It is one of the few diseases with an increasing mortality rate and by 2020 it is predicted to be the third leading cause of death. The mainstays of current treatment are long acting β₂ agonists (LABAs) coupled with an increasing reliance on inhaled corticosteroids (ICS). Two LABAs (salmeterol and formoterol) are currently licensed for COPD both as monotherapy and in combination with ICS (fluticasone propionate (FP) and budesonide respectively). A comprehensive review of the risk-benefit of these medicines in COPD is provided here which concludes that there is limited efficacy for LABAs in COPD either alone or in combination with ICS and no overall modification of the disease process. However, where directly compared, combination therapy usually provides an advantage over monotherapy. Importantly the apparent effectiveness of treatment may significantly depend upon the outcome measure chosen with some measures possibly underestimating the extent of benefit. ICS benefit may also be greater in those patients who respond to treatment. Set against this benefit are recent concerns that a number of issues related to the clinical trial design such as prior use of ICS and different withdrawal rates between groups may be significantly influencing results. Furthermore there is no evidence of a dose response relationship with regard to ICS dose. A key issue with combination therapy is the excess risk of pneumonia conferred by the use of an ICS in this patient population. This risk does not appear to be proportional to the ICS dose but may differ between FP and budesonide. We conclude that further studies are required to identify the optimal dose of ICS, in terms of both risk and benefit, and to confirm their benefit in steroid naïve patients. Furthermore it will be important to determine whether the risk of pneumonia is apparent with both FP and budesonide and to identify factors which may predict steroid responsiveness in COPD. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Improvements to the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Tauxe, L.; Koppers, A. A. P.; Constable, C.; Jonestrask, L.

2015-12-01

The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of data uploading and editing, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Online data editing is now available and the need for proprietary spreadsheet software is therefore entirely negated. The data owner can change values in the database or delete entries through an HTML 5 web interface that resembles typical spreadsheets in behavior and uses. Additive uploading now allows for additions to data sets to be uploaded with a simple drag and drop interface. Searching the database has improved with the addition of more sophisticated search parameters and with the facility to use them in complex combinations. A comprehensive summary view of a search result has been added for increased quick data comprehension while a raw data view is available if one desires to see all data columns as stored in the database. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. MagIC data associated with individual contributions or from online searches may be downloaded in the tab delimited MagIC text file format for susbsequent offline use and analysis. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

The Correlation Between Candida Colonization of Distinct Body Sites and Invasive Candidiasis in Emergency Intensive Care Units: Statistical and Molecular Biological Analysis.

PubMed

Li, Zhen; Jiang, Cen; Dong, Danfeng; Zhang, Lihua; Tian, Yuan; Ni, Qi; Mao, Enqiang; Peng, Yibing

2016-08-01

Both statistical and molecular biological methods were used to evaluate the association between Candida colonization of different body sites and invasive candidiasis (IC) and analyse the potential infection sources of IC. Candida surveillance cultures from the urine, sputum, rectum and skin were performed on patients admitted to an emergency intensive care units (EICU) of a tertiary care hospital in Shanghai, China, from February 2014 to January 2015. Specimens were collected once a week at admission and thereafter. The patients' clinical data were collected, and Candida isolates were genotyped using polymorphic microsatellite markers. A total of 111 patients were enrolled. Patients with positive urine (23.3 vs. 2.5 %, p = 0.001) and rectal swab (13.6 vs. 0 %, p = 0.010) cultures were more likely to develop IC. However, the risk for IC was not significantly different among patients with and without respiratory (10.0 vs. 5.8 %, p = 0.503) and skin (33.3 vs. 6.5 %, p = 0.056) colonization. Gene microevolution frequently occurred at rectal swab and urine sites, and IC with possible source of infection was caused by rectal isolates (2/7), urine isolates (4/7) and sputum isolate (1/7).The colonization of gut and urinary tract maybe more relevant indicators of IC, which should be taken into consideration when selecting practical body sites for Candida surveillance cultures.

TDR method for determine IC's parameters

NASA Astrophysics Data System (ADS)

Timoshenkov, V.; Rodionov, D.; Khlybov, A.

2016-12-01

Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

PubMed

Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

2013-04-01

Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

Behavioral Treatment of Chronic Insomnia in Older Adults: Does Nocturia Matter?

PubMed Central

Tyagi, Shachi; Resnick, Neil M.; Perera, Subashan; Monk, Timothy H.; Hall, Martica H.; Buysse, Daniel J.

2014-01-01

Objective: To evaluate the impact of nocturia on the therapeutic response of chronic insomnia to behavioral treatment in older adults. Methods: Secondary analysis of a randomized clinical trial designed to assess the efficacy of brief behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in 79 community-dwelling older adults with chronic insomnia. For the current analysis, participants were stratified into 2 groups: those with self-reported nocturia at baseline i.e., ≥ 1 void/night (N = 30; 16 IC, 14 BBTI) and those without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and polysomnography Results: Individuals without baseline nocturia responded well to BBTI with significant decrease in sleep latency, wake after sleep onset, and total sleep time assessed by sleep diary and actigraphy; these changes were significantly greater than those in the IC group. In comparison, changes in the same sleep parameters among participants with nocturia were not significantly different from the IC control. Although BBTI showed significant improvement in sleep quality in groups with and without nocturia (as assessed by PSQI and sleep diary), the effect size of these improvements was larger in those without nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality d = 0.83 vs. 0.51). Conclusions: These secondary analyses suggest that brief behavioral treatment of insomnia may be more efficacious in improving insomnia in participants without nocturia. Addressing nocturia may improve the efficacy of behavioral insomnia treatment. Citation: Tyagi S; Resnick NM; Perera S; Monk TH; Hall MH; Buysse DJ. Behavioral treatment of chronic insomnia in older adults: does nocturia matter? SLEEP 2014;37(4):681-687. PMID:24899759

Synthesis, characterization and anticancer studies of Ni(II), Pd(II) and Pt(II) complexes with Schiff base derived from N-methylhydrazinecarbothioamide and 2-hydroxy-5-methoxy-3-nitrobenzaldehyde

NASA Astrophysics Data System (ADS)

Arafath, Md. Azharul; Adam, Farook; Razali, Mohd. R.; Ahmed Hassan, Loiy E.; Ahamed, Mohamed B. Khadeer; Majid, Amin Malik S. A.

2017-02-01

A carbothioamide NSO tridentate Schiff base ligand (HL) and its square planar complexes Na[NiLOAc], Na[PdLOAc] and [PtLdmso] have been synthesized and characterized on the basis of melting point, elemental analysis, FT-IR, 1H NMR, 13C NMR, UV-Vis spectra. The structure of HL was elucidated with X-ray diffraction analysis. In the present study, the synthesized compounds were evaluated for their anticancer properties against three human cancer cell lines breast cancer (MCF-7), cervical (Hela), and colon (HCT-116). In addition, the cytotoxicity of the synthesized compounds was tested on a normal human cell line (human endothelial cell line EA.hy926). Among the tested compounds, the complex [NiLOAc] excelled in halting proliferation of the cervical and colon cancer cells with median inhibitory concentration (IC50) values of 28.33 and 34.4 μM, respectively. The complex, [PdLOAc] demonstrated selective cytotoxicity against breast cancer line MCF-7 with IC50 = 47.5 μM, while HL showed inhibitory effect against colon cancer cell line (HCT-116) with IC50 = 55.66 μM. The complex, [PtLdmso] showed mild activity against breast cancer (MCF-7) and cervical cancer (Hela) cells with IC50 = 64.44 and 68.3 μM, respectively, whereas, it displayed insignificant cytotoxicity against human endothelial cells (EA.hy926) with IC50 > 200 μM. Cancer cells treated with [NiLOAc] showed apoptotic features such as membrane blebbing and DNA condensation. Thus, the findings of the present study demonstrated that the series of metal complexes of HL could form the new lead for development of cancer chemotherapies to treat human cervical, breast and colon malignancies.

Professional deontology and medical practice in prisons.

PubMed

García-Guerrero, J; Vera-Remartínez, E J

2015-01-01

To study the knowledge on professional deontology amongst doctors in prisons. Descriptive, transversal and multi-centre study. Labour, collegiate, social, demographic and deontological variables were collected. A descriptive analysis of the variables was performed. A bivariate analysis was made by binary logistic regression models, attending to the odds ratio, and assuming a 95% confidence interval. Data was processed by SPSS v.20 software. 118 doctors replied. 68 men (57.6%), with an average age of 51 years (50-53). 100 know about the Deontology Committee (84.7%), but just 77 (65.3%) know its functions properly. 42 (35.6%) know about the existence of the Deontological Code, and 37 (31.3%) have read and apply it. Those who made a correct definition of deontology do find more deontological issues in their daily work [23(46.9%) vs. 18(26.1%); OR: 2.506; IC95%: 1.153-5.451; p=0.020] and would denounce a colleague more often to the Medical Association [40(81.6%) vs. 42 (60.9%); OR: 2.857; IC95%: 1.197-6.819; p=0.018]. Older ones know more about the deontology commissions' functions [54(73%) vs. 23(52.3%); OR: 2.465; IC95%: 1.127-5.394; p=0.024] and have already denounced situations to the Medical Association [27(36.5% vs. 5(11.4%); OR: 4.481; IC95%: 1.577-12.733; p=0.005], but think that a different Care Ethics Committee is unnecessary [57(77%) vs. 42(95.5%); OR: 0.160; IC95%: 0.035- 0.729; p=0.018]. Prison doctors know little about what professional deontology really is. This knowledge increases with age in the profession and is associated with an increased perception of deontological issues in daily practice.

Is the SMART approach better than other treatment approaches for prevention of asthma exacerbations? A meta-analysis.

PubMed

Agarwal, R; Khan, A; Aggarwal, A N; Gupta, D

2009-12-01

The combination of inhaled corticosteroids (ICS) and long-acting beta2 agonists (LABA) has been used as a single inhaler both for maintenance and reliever therapy in asthma, the SMART approach. The administration of additional CS with each reliever inhalation in response to symptoms is expected to provide better control of airway inflammation. The aim of this meta-analysis was to evaluate the efficacy and safety of the SMART approach versus other approaches in the management of asthma in preventing asthma exacerbations. We searched the MEDLINE and EMBASE databases for studies that have reported exacerbations in the SMART group versus the control group. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the exacerbations in the two groups and pooled the results using a random-effects model. Our search yielded eight studies. The use of SMART approach compared to fixed-dose ICS-LABA combination significantly decreased the odds of a severe exacerbation (OR 0.65; 95% CI, 0.53-0.80) and severe exacerbation requiring hospitalization/ER treatment (OR 0.69; 95% CI, 058-0.83). The use of SMART approach compared to fixed-dose ICS also significantly decreased the odds of a severe exacerbation (OR 0.52; 95% CI, 0.45-0.61) and severe exacerbation requiring medical intervention (OR 0.52; 95% CI, 0.42-0.65). The occurrence of adverse events was similar in the two groups. There was some evidence of statistical heterogeneity. The SMART approach using formoterol-budesonide is superior in preventing exacerbations when compared to traditional therapy with fixed dose ICS or ICS-LABA combination without any increase in adverse events.

[Variables associated with the use of dental services among preschool population in Spain: a national health survey analysis].

PubMed

Barriuso Lapresa, Laura; Sanz-Barbero, Belén

2012-01-01

oral health is integral to health from the eruption of the first tooth. To achieving, it is necessary an early establishment of healthy oral habits as regular dental checkups. In developed countries, caries is the most prevalent chronic pediatric disease and it may be increasing in preschool age. a) assessing prevalence of oral health services use among Spanish preschool population, b) quantifying and analyzing the existence of variability among autonomous community and c) identifying variables associated with such use. cross-sectional study about Spanish National health Survey (2006). 2,172 children aged between 2 and 5 years (both inclusive). have gone to dental services at least once during life. sociodemographic, self-referred dental health, habits and family socioeconomic status variables. Multivariate logistic regression analysis. 20.8% of Spanish preschoolers reported had attended dental services. Probability of use increased with age (OR: 1,88; IC:1,53-2,31), frequency of daily tooth brushing (three or more times per day vrs less than once: OR: 2,94; IC: 1,47-5,87) and presence of caries (OR: 2,60; IC: 1,22-5,51). There is a socioeconomic gradient about probability of use: it increased with family socioeconomic status measured by social class (low vrs high: OR: 0,41; IC: 0,19-0,86) and maternal educational level (OR: 1,62; IC: 1,13-2,32). There was not variability in the oral health services use attributable to the autonomous community. the use of dental health services among Spanish preschool population is lower than desirable. The promotion of its use should be intensified in children from disadvantaged families.

Imbalanced spontaneous brain activity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression.

PubMed

Zhang, Xiaocui; Di, Xin; Lei, Hui; Yang, Juan; Xiao, Jing; Wang, Xiang; Yao, Shuqiao; Rao, Hengyi

2016-07-01

The hopelessness theory of depression posits that individuals with negative cognitive styles are at risk of developing depression following negative life events. The purpose of this work was to examine whether individuals with cognitive vulnerability to depression (CVD) exhibit similar spontaneous brain activity patterns as compared to patients with major depressive disorder (MDD). Subjects with CVD (N=32), drug-naïve first-episode patients with major depressive disorder (N=32), and sex-, age- and education-matched healthy controls (HCs; N=35) were subjected to resting state functional magnetic resonance imaging (RS-fMRI) and amplitudes of low-frequency fluctuation (ALFF) was compared between the groups. Pearson correlation analysis was performed between regional ALFFs and psychometric scores, namely the Cognitive Style Questionnaire (CSQ) and the Center for Epidemiologic Studies Depression (CES-D) scale scores. Significant group differences in ALFF values were observed bilaterally in the orbitofrontal cortex (OFC) and insular cortex (IC), and in the left fusiform gyrus (FFG). Compared to HCs, CVD subjects had reduced ALFFs in the bilateral OFC and increased ALFF in the bilateral IC and the left FFG, which were similar to the differences observed between the HCs and MDD patients. Compared to MDD patients, CVD subjects showed significant reduced ALFF values in right IC. Additionally, CSQ scores for the CVD group correlated with ALFF values in the left IC. We did not conduct a longitudinal study. Our findings were limited in cross-sectional analysis. A hypoactive OFC and hyperactive IC in a resting-state may underlie an imbalance in the spontaneous brain activity in orbitofrontal-insular circuits, and these differences may represent a trait-related marker of vulnerability to depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Techniques for the inorganic analysis in a controlled ecological life support system

NASA Technical Reports Server (NTRS)

1983-01-01

Sample preparation, instrumental analysis, a direct injection device for IC/ICP interfacing, a hydraulic jet bend impaction device, monodisperse aerosol generator, and low gravity environments are discussed.

Mastery versus the standard proficiency target for basic laparoscopic skill training: effect on skill transfer and retention.

PubMed

Kolozsvari, Nicoleta O; Kaneva, Pepa; Brace, Chantalle; Chartrand, Genevieve; Vaillancourt, Marilou; Cao, Jiguo; Banaszek, Daniel; Demyttenaere, Sebastian; Vassiliou, Melina C; Fried, Gerald M; Feldman, Liane S

2011-07-01

Little evidence exists to guide educators in the best way to implement simulation within surgical skills curricula. This study investigated whether practicing a basic Fundamentals of Laparoscopic Surgery (FLS) simulator task [peg transfer (PT)] facilitates learning a more complex skill [intracorporeal suturing (ICS)] and compared the effect of PT training to mastery with training to the passing level on PT retention and on learning ICS. For this study, 98 surgically naïve subjects were randomized to one of three PT training groups: control, standard training, and overtraining. All the participants then trained in ICS. The learning curves for ICS were analyzed by estimating the learning plateau and rate using nonlinear regression. Skill retention was assessed by retesting participants 1 month after training. The groups were compared using analysis of variance (ANOVA). Effectiveness of skill transfer was calculated using the transfer effectiveness ratio (TER). Data are presented as mean±standard deviation (p<0.05). The study was completed by 77 participants (28 control, 26 standard, and 23 overtrained subjects). The ICS learning plateau rose with increasing PT training (452±10 vs. 459±10 vs. 467±10; p<0.01). Increased PT training was associated with a trend toward higher initial ICS scores (128±107 vs. 127±110 vs. 183±106; p=0.13) and faster learning rates (15±4 vs. 14±4 vs. 13±4 trials; p=0.10). At retention, there were no differences in PT scores (p=0.5). The PT training took 20±10 min for standard training and 39±20 min for overtraining (p<0.01). Overtrained participants saved 11±5 min in ICS training compared with the control subjects (p=0.04). However, TER was 0.165 for the overtraining group and 0.160 for the standard training group, suggesting that PT overtraining took longer than the time saved on ICS training. For surgically naïve subjects, part-task training with PT alone was associated with slight improvements in the learning curve for ICS. However, overtraining with PT did not improve skill retention, and peg training alone was not an efficient strategy for learning ICS.

Chronotype differences in cortical thickness: grey matter reflects when you go to bed.

PubMed

Rosenberg, Jessica; Jacobs, Heidi I L; Maximov, Ivan I; Reske, Martina; Shah, N J

2018-06-15

Based on individual circadian cycles and associated cognitive rhythms, humans can be classified via standardised self-reports as being early (EC), late (LC) and intermediate (IC) chronotypes. Alterations in neural cortical structure underlying these chronotype differences have rarely been investigated and are the scope of this study. 16 healthy male ECs, 16 ICs and 16 LCs were measured with a 3 T MAGNETOM TIM TRIO (Siemens, Erlangen) scanner using a magnetization prepared rapid gradient echo sequence. Data were analysed by applying voxel-based morphometry (VBM) and vertex-wise cortical thickness (CTh) analysis. VBM analysis revealed that ECs showed significantly lower grey matter volumes bilateral in the lateral occipital cortex and the precuneus as compared to LCs, and in the right lingual gyrus, occipital fusiform gyrus and the occipital pole as compared to ICs. CTh findings showed lower grey matter volumes for ECs in the left anterior insula, precuneus, inferior parietal cortex, and right pars triangularis than for LCs, and in the right superior parietal gyrus than for ICs. These findings reveal that chronotype differences are associated with specific neural substrates of cortical thickness, surface areas, and folding. We conclude that this might be the basis for chronotype differences in behaviour and brain function. Furthermore, our results speak for the necessity of considering "chronotype" as a potentially modulating factor in all kinds of structural brain-imaging experiments.

Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener.

PubMed

Ghanta, Srijani; Banerjee, Anindita; Poddar, Avijit; Chattopadhyay, Sharmila

2007-12-26

At 0.1 mg/mL, the ethyl acetate extract (EAE) of the crude 85% methanolic extract (CAE) of Stevia rebaudiana leaves exhibited preventive activity against DNA strand scission by *OH generated in Fenton's reaction on pBluescript II SK (-) DNA. Its efficacy is better than that of quercetin. The radical scavenging capacity of CAE was evaluated by the DPPH test (IC50=47.66+/-1.04 microg/mL). EAE was derived from CAE scavenged DPPH (IC50=9.26+/-0.04 microg/mL), ABTS+ (IC50=3.04+/-0.22 microg/mL) and *OH (IC50=3.08+/-0.19 microg/mL). Additionally, inhibition of lipid peroxidation induced with 25 mM FeSO 4 on rat liver homogenate as a lipid source was noted with CAE (IC50=2.1+/-1.07 mg/mL). The total polyphenols and total flavonoids of EAE were 0.86 mg gallic acid equivalents/mg and 0.83 mg of quercetin equivalents/mg, respectively. Flavonoids, isolated from EAE, were characterized as quercetin-3-O-arabinoside, quercitrin, apigenin, apigenin-4-O-glucoside, luteolin, and kaempferol-3-O-rhamnoside by LC-MS and NMR analysis. These results indicate that Stevia rebaudiana may be useful as a potential source of natural antioxidants.

Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana.

PubMed

Shi, Qun; Sun, Yi-Wei; Meng, Dali

2017-01-15

With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1-3) and six known ones (4-9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC 50 8.1μmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC 50 values of 12.5, 12.0 and 18.7μmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC 50 11.9μmol/L) and 8 (IC 50 9.4μmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC 50 values of 28.2 and 29.8μmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

XMM-Newton observations of the supernova remnant IC 443. II. Evidence of stellar ejecta in the inner regions

NASA Astrophysics Data System (ADS)

Troja, E.; Bocchino, F.; Miceli, M.; Reale, F.

2008-07-01

Aims: We investigate the spatial distribution of the physical and chemical properties of the hot X-ray emitting plasma of the supernova remnant IC 443, to derive important constraints on its ionization stage, on the progenitor supernova explosion, on the age of the remnant, and its physical association with a close pulsar wind nebula. Methods: We present XMM-Newton images of IC 443, a median photon energy map, silicon and sulfur equivalent width maps, and a spatially resolved spectral analysis of a set of homogeneous regions. Results: The hard X-ray thermal emission (1.4-5.0 keV) of IC 443 displays a centrally-peaked morphology, its brightness peaks being associated with hot (kT > 1 keV) X-ray emitting plasma. A ring-shaped structure, characterized by high values of equivalent widths and median photon energy, encloses the PWN. Its hard X-ray emission is spectrally characterized by a collisional ionization equilibrium model, and strong emission lines of Mg, Si, and S, requiring oversolar metal abundances. Dynamically, the location of the ejecta ring suggests an SNR age of ~4000 yr. The presence of overionized plasma in the inner regions of IC 443, addressed in previous works, is much less evident in our observations.

Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort

PubMed Central

Hampshire, Daniel J.; Abuzenadah, Adel M.; Cartwright, Ashley; Al-Shammari, Nawal S.; Coyle, Rachael E.; Eckert, Michaela; Al-Buhairan, Ahlam M.; Messenger, Sarah L.; Budde, Ulrich; Gürsel, Türkiz; Ingerslev, Jørgen; Peake, Ian R.; Goodeve, Anne C.

2014-01-01

Summary Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17–18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships. PMID:23702511

Anti-complementary neutral polysaccharides from leaves of Artemisia princeps.

PubMed

Zhao, Q C; Kiyohara, H; Yamada, H

1994-01-01

The three anti-complementary neutral polysaccharides, IA-1, IB-1 and IC-1, were purified from the leaves of Artemisia princeps by anion-exchange chromatography, gel filtration and affinity chromatography. The order of the anti-complementary activity was IA-1 > IB-1 > IC-1. The polysaccharides appeared to be homogeneous from the results of gel filtration, HPLC and electrophoresis. The M(r)s of IA-1 IB-1 and IC-1 were estimated to be 56,000, 16,000, and 7000, respectively, by HPLC. IA-1 consisted mainly of arabinose (Ara), galactose (Gal) and glucose (Glc) in molar ratios of 1.8:1.0:0.9, whereas IB-1 and IC-1 were composed mainly of Ara, mannose (Man), Gal and Glc in molar ratios of 3.5:0.8:1.0:0.8 and 2.3:3.5:1.0:3.2, respectively. Methylation analysis, 13C NMR and enzymic digestion suggested that IA-1 mainly contained alpha-L-(1-->3,5)-arabinan, beta-D-(1-->6)-linked Gal and beta-D-(1-->3)-linked Glc. IB-1 also consisted mainly of alpha-L-(1-->3,5)-arabinan and beta-D-(1-->6)-linked Gal, whereas IC-1 was composed mainly of beta-D-(1-->4)- linked Glc and alpha- or beta-D-(1-->4)-linked Man.

A Novel Two-Step Hierarchial Quantitative Structure-Activity ...

EPA Pesticide Factsheets

Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET ; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments) . The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models t

Effect of echolocation behavior-related constant frequency-frequency modulation sound on the frequency tuning of inferior collicular neurons in Hipposideros armiger.

PubMed

Tang, Jia; Fu, Zi-Ying; Wei, Chen-Xue; Chen, Qi-Cai

2015-08-01

In constant frequency-frequency modulation (CF-FM) bats, the CF-FM echolocation signals include both CF and FM components, yet the role of such complex acoustic signals in frequency resolution by bats remains unknown. Using CF and CF-FM echolocation signals as acoustic stimuli, the responses of inferior collicular (IC) neurons of Hipposideros armiger were obtained by extracellular recordings. We tested the effect of preceding CF or CF-FM sounds on the shape of the frequency tuning curves (FTCs) of IC neurons. Results showed that both CF-FM and CF sounds reduced the number of FTCs with tailed lower-frequency-side of IC neurons. However, more IC neurons experienced such conversion after adding CF-FM sound compared with CF sound. We also found that the Q 20 value of the FTC of IC neurons experienced the largest increase with the addition of CF-FM sound. Moreover, only CF-FM sound could cause an increase in the slope of the neurons' FTCs, and such increase occurred mainly in the lower-frequency edge. These results suggested that CF-FM sound could increase the accuracy of frequency analysis of echo and cut-off low-frequency elements from the habitat of bats more than CF sound.

Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution.

PubMed

Hung, Man-Jung; Su, Tsung-Hsien; Lin, Yi-Hao; Huang, Wen-Chu; Lin, Tzu-Yin; Hsu, Chun-Shuo; Chuang, Fei-Chi; Tsai, Ching-Pei; Shen, Pao-Sheng; Chen, Gin-Den

2014-09-01

Intravesical instillation with a hyaluronic acid (HA) solution is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), but its impact on sexual functioning of patients is not known. The aim of this study was to evaluate the changes in sexual function of women with refractory IC/BPS who underwent a second-line intravesical HA therapy. A total of 103 women diagnosed with refractory IC/BPS were enrolled in this prospective, multicenter study. Sexual function was evaluated using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-9). Bladder-related symptoms and bother were assessed by the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), and a pain visual analog scale (VAS), respectively. Data were analyzed with univariate methods or multivariate logistic regression analysis accordingly. Changes in PISQ-9, ICSI, ICPI, and pain VAS scores after treatment were assessed. Mean age and duration of symptoms was 43.6 ± 11.8 and 5.1 ± 5.0 years, respectively. ICSI, ICPI, and pain VAS scores were significantly (P < 0.001) improved after 1 month and 6 months of treatment. Of the 87 (84.5%) sexually active women evaluated, PISQ-9 total scores improved significantly (P < 0.001) from the baseline (mean 18.9 ± 6.4), after 1 month (20.4 ± 5.8), and 6-months (21.5 ± 5.6) of treatment. Significantly improved PISQ-9 items included "dyspareunia" (P < 0.001) and "negative reactions" (P = 0.015) during sexual intercourse, and "intensity" (P < 0.001) of sexual orgasms. After a logistic regression analysis, we found that a baseline PISQ-9 score was negatively correlated with the duration of IC/BPS symptoms (P = 0.022). Meanwhile, the changes in PISQ-9 scores were positively correlated with the reduction in ICSI scores after treatment (P = 0.045). Intravesical HA is an effective treatment for refractory IC/BPS. A longer duration of IC/BPS symptoms may be a predictor of poor sexual function. However, intravesical HA may improve sexual function along with the reduction of IC/BPS symptoms. © 2014 International Society for Sexual Medicine.

Electromigration failures under bidirectional current stress

NASA Astrophysics Data System (ADS)

Tao, Jiang; Cheung, Nathan W.; Hu, Chenming

1998-01-01

Electromigration failure under DC stress has been studied for more than 30 years, and the methodologies for accelerated DC testing and design rules have been well established in the IC industry. However, the electromigration behavior and design rules under time-varying current stress are still unclear. In CMOS circuits, as many interconnects carry pulsed-DC (local VCC and VSS lines) and bidirectional AC current (clock and signal lines), it is essential to assess the reliability of metallization systems under these conditions. Failure mechanisms of different metallization systems (Al-Si, Al-Cu, Cu, TiN/Al-alloy/TiN, etc.) and different metallization structures (via, plug and interconnect) under AC current stress in a wide frequency range (from mHz to 500 MHz) has been study in this paper. Based on these experimental results, a damage healing model is developed, and electromigration design rules are proposed. It shows that in the circuit operating frequency range, the "design-rule current" is the time-average current. The pure AC component of the current only contributes to self-heating, while the average (DC component) current contributes to electromigration. To ensure longer thermal-migration lifetime under high frequency AC stress, an additional design rule is proposed to limit the temperature rise due to self-joule heating.

[Prospective observational study of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with chronic renal failure].

PubMed

Ben Mahmoud, Lobna; Ghozzi, Hanene; Kammoun, Khawla; Hakim, Ahmed; Kharrat, Mahmoud; Ben Hmida, Mohamed; Jarraya, Faical; Sahnoun, Zouheir; Zeghal, Khaled; Hachicha, Jamil

2013-04-01

To study the incidence and risk factors of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with hypertension and preexisting chronic renal failure. Two-months prospective observational study was used including all hospitalized patients older than 18 years with a history of hypertension, non-dialyzed chronic renal failure and who had angiotensin converting enzyme prescription at the time of the admission. Hyperkalemia greater than or equal to 5 mmol/L was detected in these patients. The studied variables were demographic, clinical, biological and therapeutic. Eight patients, among 27 included, had a hyperkalemia (2963%). They were 73±15 years old. Factors that predispose to hyperkalemia were present in all patients. Hyperkalemia was associated in six cases with decompensation of renal function. The age was associated with hyperkalaemia in patients treated with angiotensin converting enzyme inhibitors (RC=1.21; IC95 1,11-1,46; P=0,021). Diabetes is a possible risk factor (OR=59 021 et, 95 0.93 to 2410, P=0.053). Compared with patients who did not develop hyperkalemia, the occurrence of hyperkalemia in patients included was associated with a longer duration of hospitalization (OR=130, 95 112 to 160, P=0. 022). The prescription of angiotensin converting enzyme inhibitors in the elderly with chronic renal failure and diabetes requires careful monitoring of serum potassium. Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Progressive Failure Analysis Methodology for Laminated Composite Structures

NASA Technical Reports Server (NTRS)

Sleight, David W.

1999-01-01

A progressive failure analysis method has been developed for predicting the failure of laminated composite structures under geometrically nonlinear deformations. The progressive failure analysis uses C(exp 1) shell elements based on classical lamination theory to calculate the in-plane stresses. Several failure criteria, including the maximum strain criterion, Hashin's criterion, and Christensen's criterion, are used to predict the failure mechanisms and several options are available to degrade the material properties after failures. The progressive failure analysis method is implemented in the COMET finite element analysis code and can predict the damage and response of laminated composite structures from initial loading to final failure. The different failure criteria and material degradation methods are compared and assessed by performing analyses of several laminated composite structures. Results from the progressive failure method indicate good correlation with the existing test data except in structural applications where interlaminar stresses are important which may cause failure mechanisms such as debonding or delaminations.

Observation of Nonthermal Emission from the Supernova Remnant IC443 with RXTE

NASA Technical Reports Server (NTRS)

Sturner, S. J.; Keohane, J. W.; Reimer, O.

2002-01-01

In this paper we present analysis of X-ray spectra from the supernova remnant IC443 obtained using the PCA on RXTE. The spectra in the 3 - 20 keV band are well fit by a two-component model consisting of thermal and nonthermal components. We compare these results with recent results of other X-ray missions and discuss the need for a cut-off in the nonthermal spectrum. Recent Chandra and XMM-Newton observations suggest that much of the nonthermal emission from IC443 can be attributed to a pulsar wind nebula. We present the results of our search for periodic emission in the RXTE PCA data. We then discuss the origin o f the nonthermal component and its possible association with the unidentified EGRET source.

Evaluation of a Progressive Failure Analysis Methodology for Laminated Composite Structures

NASA Technical Reports Server (NTRS)

Sleight, David W.; Knight, Norman F., Jr.; Wang, John T.

1997-01-01

A progressive failure analysis methodology has been developed for predicting the nonlinear response and failure of laminated composite structures. The progressive failure analysis uses C plate and shell elements based on classical lamination theory to calculate the in-plane stresses. Several failure criteria, including the maximum strain criterion, Hashin's criterion, and Christensen's criterion, are used to predict the failure mechanisms. The progressive failure analysis model is implemented into a general purpose finite element code and can predict the damage and response of laminated composite structures from initial loading to final failure.

Factors Influencing Progressive Failure Analysis Predictions for Laminated Composite Structure

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.

2008-01-01

Progressive failure material modeling methods used for structural analysis including failure initiation and material degradation are presented. Different failure initiation criteria and material degradation models are described that define progressive failure formulations. These progressive failure formulations are implemented in a user-defined material model for use with a nonlinear finite element analysis tool. The failure initiation criteria include the maximum stress criteria, maximum strain criteria, the Tsai-Wu failure polynomial, and the Hashin criteria. The material degradation model is based on the ply-discounting approach where the local material constitutive coefficients are degraded. Applications and extensions of the progressive failure analysis material model address two-dimensional plate and shell finite elements and three-dimensional solid finite elements. Implementation details are described in the present paper. Parametric studies for laminated composite structures are discussed to illustrate the features of the progressive failure modeling methods that have been implemented and to demonstrate their influence on progressive failure analysis predictions.

Ion Chromatography-on-a-chip for Water Quality Analysis

NASA Technical Reports Server (NTRS)

Kidd, R. D.; Noell, A.; Kazarians, G.; Aubrey, A. D.; Scianmarello, N.; Tai, Y.-C.

2015-01-01

We report progress towards developing a Micro-Electro-Mechanical Systems (MEMS)- based ion chromatograph (IC) for crewed spacecraft water analysis. This IC-chip is an offshoot of a NASA-funded effort to produce a high performance liquid chromatograph (HPLC)-chip. This HPLC-chip system would require a desalting (i.e. ion chromatography) step. The complete HPLC instrument consists of the Jet Propulsion Labortory's (JPL's) quadrupole ion trap mass spectrometer integrated with a state-of-the-art MEMS liquid chromatograph (LC) system developed by the California Institute of Technology's (Caltech's) Micromachining Laboratory. The IC version of the chip consist of an electrolysis-based injector, a separation column, two electrolysis pumps for gradient generation, mixer, and a built-in conductivity detector. The HPLC version of the chip also includes a nanospray tip. The low instrument mass, coupled with its high analytical capabilities, makes the LC chip ideally suitable for wide range of applications such as trace contaminant, inorganic analytical science and, when coupled to a mass spectrometer, a macromolecular detection system for either crewed space exploration vehicles or robotic planetary missions.

Are Interferential Electrical Stimulation and Diaphragmatic Breathing Exercises Beneficial in Children With Bladder and Bowel Dysfunction?

PubMed

Zivkovic, Vesna D; Stankovic, Ivona; Dimitrijevic, Lidija; Kocic, Mirjana; Colovic, Hristina; Vlajkovic, Marina; Slavkovic, Andjelka; Lazovic, Milica

2017-04-01

To evaluate the effects of interferential current (IC) stimulation and diaphragmatic breathing exercises (DBEs) in children with bladder and bowel dysfunction. Seventy-nine children with dysfunctional voiding and chronic constipation who were failures of primary care interventions were included in the prospective clinical study. All the children were checked for their medical history regarding lower urinary tract symptoms and bowel habits. Physical examination, including abdominal and anorectal digital examination, was performed. Children kept a bladder and bowel diary, and underwent urinalyses and urine culture, ultrasound examination of bladder and kidneys, and uroflowmetry with pelvic floor electromyography. Eligible children were divided into 3 groups (A, B, and C). All groups were assigned education and behavioral modifications. Additionally, group A underwent DBEs and IC stimulation, whereas group B received only DBEs. The treatment was conducted for 2 weeks in the clinic in all 3 groups,. The behavioral modifications and DBEs were continued at home for 1 month. Clinical manifestations, uroflowmetry parameters, and postvoided residual urine were analyzed before and after 6 weeks of therapy. After the treatment, significant improvement in defecation frequency and fecal incontinence was noticed only in group A (P < .001 and P < .05, respectively). These children demonstrated significant improvement in lower urinary tract symptoms and postvoided residual urine (P < .001 and P < .05, respectively). Bell-shaped uroflowmetry curve was observed in 73.3% of group A patients (P < .001). IC stimulation and DBEs are beneficial in chronically constipated dysfunctional voiders. Further trials are needed to define the long-term effects of this program. Copyright © 2016 Elsevier Inc. All rights reserved.

The Mediating Role of Anxiety Sensitivity in Uncontrolled Drinking: A Look at Gender-Specific Parental Influences.

PubMed

Ebbert, Ashley M; Patock-Peckham, Julie A; Luk, Jeremy W; Voorhies, Kirsten; Warner, Olivia; Leeman, Robert F

2018-05-01

Anxiety sensitivity (AS) reflects an individual's belief that experiencing anxiety will cause illness or embarrassment, and may be a reason individuals self-medicate with alcohol. Harsh or indulgent parenting could contribute to the development of AS. We examined the direct and indirect associations between parenting styles and alcohol-related variables through AS and impaired control over drinking (IC; i.e., perceived failure to adhere to limits on alcohol consumption in the future). A multiple-group structural equation model with 614 university students (344 men; 270 women) was examined. Structural invariance tests were conducted to evaluate moderation by gender. We used a bias corrected bootstrap technique to obtain the mediated effects. Father authoritarianism and mother permissiveness were directly linked to AS among women, whereas father permissiveness was directly linked to AS among men. This suggests unique parental influences based on gender regarding AS. While AS was directly linked to alcohol-related problems for both men and women, several gender-specific associations were found. AS was directly linked to IC for men but not for women. For men, father permissiveness was directly related to AS, and AS mediated the indirect link between father permissiveness and IC along both the heavy episodic drinking and alcohol-related problems pathways. Similar to other internalizing constructs (e.g., neuroticism and depression), higher AS was directly associated with less heavy episodic drinking but more alcohol-related problems. Our findings highlight the dangers of AS for men as an important correlate of under-controlled drinking behaviors. Additionally, permissive parenting of the same-gender parent was associated with AS, which is consistent with the gender-matching hypothesis. Together, these results underscore the importance of measuring the independent influence of both parents. Copyright © 2018 by the Research Society on Alcoholism.

An intercomparison of five ammonia measurement techniques

NASA Technical Reports Server (NTRS)

Williams, E. J.; Sandholm, S. T.; Bradshaw, J. D.; Schendel, J. S.; Langford, A. O.; Quinn, P. K.; Lebel, P. J.; Vay, S. A.; Roberts, P. D.; Norton, R. B.

1992-01-01

Results obtained from five techniques for measuring gas-phase ammonia at low concentration in the atmosphere are compared. These methods are: (1) a photofragmentation/laser-induced fluorescence (PF/LIF) instrument; (2) a molybdenum oxide annular denuder sampling/chemiluminescence detection technique; (3) a tungsten oxide denuder sampling/chemiluminescence detection system; (4) a citric-acid-coated denuder sampling/ion chromatographic analysis (CAD/IC) method; and (5) an oxalic-acid-coated filter pack sampling/colorimetric analysis method. It was found that two of the techniques, the PF/LIF and the CAD/IC methods, measured approximately 90 percent of the calculated ammonia added in the spiking tests and agreed very well with each other in the ambient measurements.

Standardizing Imperata cylindrica--source material for quality allergen preparations.

PubMed

Bijli, Kaiser M; Singh, B P; Sridhara, Susheela; Gaur, S N; Arora, Naveen

2002-02-01

Tropical countries experience wide variations in daytime temperature and relative humidity. This affects the quality of the source material used for allergen extracts. The present study was undertaken to standardize the processing and preservation conditions of Imperata cylindrica grass pollen. I. cylindrica (Ic) inflorescence were freeze-dried, pollens sieved out and stored at -70 degrees C (IcA). Alternatively, the inflorescence were dried at room temperature and then at 37 degrees C, pollens sieved out and stored at 4 degrees C (IcB). The extracts prepared in PBS were analyzed in vivo by skin tests and in vitro by immunochemical methods. Reduced SDS-PAGE revealed 37 protein bands in IcA extract and 23 in IcB extract. IgE immunoblot with a pool of sera from Ic hypersensitive patients showed 30 allergenic bands in IcA and 14 in IcB. Immunoblot using anti-Ic rabbit sera revealed 33 antigenic bands in IcA and 22 in IcB. In both blots, the IcA extract exhibited sharp bands and the IcB extract exhibited diffuse bands. ELISA, ELISA inhibition and skin test procedures showed that IcA extracts had a higher potency than IcB extracts. Extracts prepared from -70 degrees C processed and preserved pollens (IcA) are allergenically more potent and contain a greater number of major and minor allergens than IcB extracts.

Sulfated polysaccharides from Loligo vulgaris skin: potential biological activities and partial purification.

PubMed

Abdelmalek, Baha Eddine; Sila, Assaâd; Krichen, Fatma; Karoud, Wafa; Martinez-Alvarez, Oscar; Ellouz-Chaabouni, Semia; Ayadi, Mohamed Ali; Bougatef, Ali

2015-01-01

The characteristics, biological properties, and purification of sulfated polysaccharides extracted from squid (Loligo vulgaris) skin were investigated. Their chemical and physical characteristics were determined using X-ray diffraction and infrared spectroscopic analysis. Sulfated polysaccharides from squid skin (SPSS) contained 85.06% sugar, 2.54% protein, 1.87% ash, 8.07% sulfate, and 1.72% uronic acid. The antioxidant properties of SPSS were investigated based on DPPH radical-scavenging capacity (IC50 = 19.42 mg mL(-1)), hydrogen peroxide-scavenging activity (IC50 = 0.91 mg mL(-1)), and β-carotene bleaching inhibition (IC50 = 2.79 mg mL(-1)) assays. ACE-inhibitory activity of SPSS was also investigated (IC50 = 0.14 mg mL(-1)). Further antimicrobial activity assays indicated that SPSS exhibited marked inhibitory activity against the bacterial and fungal strains tested. Those polysaccharides did not display hemolytic activity towards bovine erythrocytes. Fractionation by DEAE-cellulose column chromatography showed three major absorbance peaks. Results of this study suggest that sulfated polysaccharides from squid skin are attractive sources of polysaccharides and promising candidates for future application as dietary ingredients.

AGB stars as tracers to IC 1613 evolution.

NASA Astrophysics Data System (ADS)

Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

The Density Jump at the Inner Core Boundary in the Eastern and Western Hemispheres

NASA Astrophysics Data System (ADS)

Krasnoshchekov, D. N.; Ovtchinnikov, V. M.

2018-02-01

The results of analysis of more than 1300 new PKiKP/PcP amplitude ratios measured in Southeast Asia and South America at the epicentral distances of 3.2°-35.2° are presented. The density jump in the Eastern Hemisphere of the Earth's inner core (IC) is 0.3 g/cm3, and it is 0.9 g/cm3 in the Western one. Taking the large discrepancy in the obtained estimates into consideration, maintenance of such large lateral variations in the mosaic properties of the IC reflecting surface requires considerable variations in the thermodynamic parameters (mostly temperature) of the inner-outer core transition. However, if the observed asymmetry in the density jump distribution is of a global character, the data presented support the translation model of the IC dynamics. This model implies IC crystallization in the Western Hemisphere and melting in the Eastern one, not vice versa, as suggested by another geodynamic model based on thermochemical convection in the outer core and the thermal balance of the core-mantle system.

Effecting aging time of epoxy molding compound to molding process for integrated circuit packaging

NASA Astrophysics Data System (ADS)

Tachapitunsuk, Jirayu; Ugsornrat, Kessararat; Srisuwitthanon, Warayoot; Thonglor, Panakamon

2017-09-01

This research studied about effecting aging time of epoxy molding compound (EMC) that effect to reliability performance of integrated circuit (IC) package in molding process. Molding process is so important of IC packaging process for protecting IC chip (or die) from temperature and humidity environment using encapsulated EMC. For general molding process, EMC are stored in the frozen at 5°C and left at room temperature at 25 °C for aging time on self before molding of die onto lead frame is 24 hours. The aging time effect to reliability performance of IC package due to different temperature and humidity inside the package. In experiment, aging time of EMC were varied from 0 to 24 hours for molding process of SOIC-8L packages. For analysis, these packages were tested by x-ray and scanning acoustic microscope to analyze properties of EMC with an aging time and also analyzed delamination, internal void, and wire sweep inside the packages with different aging time. The results revealed that different aging time of EMC effect to properties and reliability performance of molding process.

Urchin-like gold nanoparticle-based immunochromatographic strip test for rapid detection of fumonisin B1 in grains.

PubMed

Ren, Wenjie; Huang, Zhibing; Xu, Yang; Li, Yanping; Ji, Yanwei; Su, Baowei

2015-09-01

An immunochromatographic strip (ICS) using urchin-like gold nanoparticles (UGNs) for sensitive detection of fumonisin B1 (FB1) was developed to meet the requirement for rapidly monitoring FB1 in grain samples. The sensitivity of the ICS was 5.0 ng/mL, which represents a fourfold increase in sensitivity over conventional strip preparation using colloidal gold as the antibody-labeled probe. Analysis of FB1 in grain samples showed that data obtained from the strip tests were in a good agreement with those obtained from HPLC and enzyme-linked immunosorbent assays (ELISAs). This qualitative test did not require any specialized equipment, and the detection time was less than 5 min, which is suitable for on-site testing of FB1 in grain samples. Overall, to our knowledge, this is the first report of using a UGN as the antibody-labeled probe for sensitive detection of FB1 in grains using an ICS. Graphical Abstract Preparation of ICS using conventional colloidal gold and urchin-like gold nanoparticle, respectively.

Study of antileishmanial activity of 2-aminobenzoyl amino acid hydrazides and their quinazoline derivatives.

PubMed

Khattab, Sherine Nabil; Haiba, Nesreen Saied; Asal, Ahmed Mosaad; Bekhit, Adnan A; Guemei, Aida A; Amer, Adel; El-Faham, Ayman

2017-02-15

A new small library of 2-aminobenzoyl amino acid hydrazide derivatives and quinazolinones derivatives was synthesized and fully characterized by IR, NMR, and elemental analysis. The activity of the prepared compounds on the growth of Leishmania aethiopica promastigotes was evaluated. 2-Benzoyl amino acid hydrazide showed higher inhibitory effect than the quinazoline counterpart. The in vitro antipromastigote activity demonstrated that compounds 2a, 2b, 2f and 4a had IC 50 better than standard drug miltefosine and comparable activity to amphotericin B deoxycholate, which indicates their high antileishmanial activity against Leishmania. aethiopica. Among the prepared compounds; 2-amino-N-(6-hydrazinyl-6-oxohexyl)benzamide 2f (IC 50 =0.051μM) has the best activity, 154 folds more active than reference standard drug miltefosine (IC 50 =7.832μM), and half fold the activity of amphotericin B (IC 50 =0.035μM). In addition, this compound was safe and well tolerated by experimental animals orally up to 250mg/kg and parenterally up to 100mg/kg. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of Shigella in Milk and Clinical Samples by Magnetic Immunocaptured-Loop-Mediated Isothermal Amplification Assay

PubMed Central

Zhang, Liding; Wei, Qiujiang; Han, Qinqin; Chen, Qiang; Tai, Wenlin; Zhang, Jinyang; Song, Yuzhu; Xia, Xueshan

2018-01-01

Shigella is an important human food-borne zoonosis bacterial pathogen, and can cause clinically severe diarrhea. There is an urgent need to develop a specific, sensitive, and rapid methodology for detection of this pathogen. In this study, loop-mediated isothermal amplification (LAMP) combined with magnetic immunocapture assay (IC-LAMP) was first developed for the detection of Shigella in pure culture, artificial milk, and clinical stool samples. This method exhibited a detection limit of 8.7 CFU/mL. Compared with polymerase chain reaction, IC-LAMP is sensitive, specific, and reliable for monitoring Shigella. Additionally, IC-LAMP is more convenient, efficient, and rapid than ordinary LAMP, as it is more efficiently enriches pathogen cells without extraction of genomic DNA. Under isothermal conditions, the amplification curves and the green fluorescence were detected within 30 min in the presence of genomic DNA template. The overall analysis time was approximately 1 h, including the enrichment and lysis of the bacterial cells, a significantly short detection time. Therefore, the IC-LAMP methodology described here is potentially useful for the efficient detection of Shigella in various samples. PMID:29467730

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters.

PubMed

György, Bence; Módos, Károly; Pállinger, Eva; Pálóczi, Krisztina; Pásztói, Mária; Misják, Petra; Deli, Mária A; Sipos, Aron; Szalai, Anikó; Voszka, István; Polgár, Anna; Tóth, Kálmán; Csete, Mária; Nagy, György; Gay, Steffen; Falus, András; Kittel, Agnes; Buzás, Edit I

2011-01-27

Numerous diseases, recently reported to associate with elevated microvesicle/microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidin-biotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic light-scattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease.

Fast filtration sampling protocol for mammalian suspension cells tailored for phosphometabolome profiling by capillary ion chromatography - tandem mass spectrometry.

PubMed

Kvitvang, Hans F N; Bruheim, Per

2015-08-15

Capillary ion chromatography (capIC) is the premium separation technology for low molecular phosphometabolites and nucleotides in biological extracts. Removal of excessive amounts of salt during sample preparation stages is a prerequisite to enable high quality capIC separation in combination with reproducible and sensitive MS detection. Existing sampling protocols for mammalian cells used for GC-MS and LC-MS metabolic profiling can therefore not be directly applied to capIC separations. Here, the development of a fast filtration sampling protocol for mammalian suspension cells tailored for quantitative profiling of the phosphometabolome on capIC-MS/MS is presented. The whole procedure from sampling the culture to transfer of filter to quenching and extraction solution takes less than 10s. To prevent leakage it is critical that a low vacuum pressure is applied, and satisfactorily reproducibility was only obtained by usage of a vacuum pressure controlling device. A vacuum of 60mbar was optimal for filtration of multiple myeloma Jjn-3 cell cultures through 5μm polyvinylidene (PVDF) filters. A quick deionized water (DI-water) rinse step prior to extraction was tested, and significantly higher metabolite yields were obtained during capIC-MS/MS analyses in this extract compared to extracts prepared by saline and reduced saline (25%) washing steps only. In addition, chromatographic performance was dramatically improved. Thus, it was verified that a quick DI-water rinse is tolerated by the cells and can be included as the final stage during filtration. Over 30 metabolites were quantitated in JJN-3 cell extracts by using the optimized sampling protocol with subsequent capIC-MS/MS analysis, and up to 2 million cells can be used in a single filtration step for the chosen filter and vacuum pressure. The technical set-up is also highly advantageous for microbial metabolome filtration protocols after optimization of vacuum pressure and washing solutions, and the reduced salt content of the extract will also improve the quality of LC-MS analysis due to lower salt adduct ion formation. Copyright © 2015 Elsevier B.V. All rights reserved.

Trypanocidal activity of polysaccharide extract from Genipa americana leaves.

PubMed

Souza, Racquel Oliveira da Silva; Sousa, Paloma Leão; Menezes, Ramon Róseo Paula Pessoa Bezerra de; Sampaio, Tiago Lima; Tessarolo, Louise Donadello; Silva, Francisca Crislandia Oliveira; Pereira, Maria Gonçalves; Martins, Alice Maria Costa

2018-01-10

The parts of the Genipa americana (Rubiaceae) tree, also known as "jenipapo" or "jenipapeiro", has been used in traditional Medicine in parasitic and bacterial infections. Thus, the experimental evolution of the antiparasitic activity of polysaccharide extracts from Genipa americana leaves, and correlation with antiparasitic and popular use is important. To evaluate the effect of polysaccharide extract obtained from Genipa americana leaves on all Trypanosoma cruzi (Y strain: benznidazole-resistant) developmental forms, a protozoan that causes Chagas' disease. An extract rich in polysaccharides was obtained from the leaves of Genipa americana (GaEPL) by associating depigmentation in methanol followed by extraction of polysaccharides in NaOH and precipitation with ethanol. Cytotoxicity to mammalian cells (LLC-MK2) was determined using an MTT assay. Antiparasitic activity was evaluated against epimastigote, trypomastigote and amastigote forms of T. cruzi. Cell-death mechanism was determined in epimastigote forms by flow cytometry analysis after FITC-annexin V (Ax), 7-AAD, and H2DCFDA staining. Striking morphological changes were observed by scanning electron microscope. GaEPL (6.5% yield; 54.6% total carbohydrate; 21.1% uronic acid and 12% protein), inhibited all T. cruzi developmental forms, epimastigotes after periods of 24h (IC 50 = 740 ± 0.075µg/mL), 48h (IC 50 = 710 ± 0.053µg/mL) and 72h (IC 50 = 870 ± 0.052µg/mL) of incubation; trypomastigotes (IC 50 = 470 ± 0.082µg/mL) after periods of 24h and intracellular amastigotes (IC 50/2 = 235 or IC 50 = 470µg/mL) after periods of 24 and 48h of incubation, with no toxicity on LLC-MK2 cells at the used concentrations. Analysis of the possible action mechanism in the parasites suggested cell death by necrosis with the involvement of reactive oxygen species (ROS). The scanning electron microscopy (SEM) confirmed T. cruzi death by necrosis. GaEPL showed significant activity against the epimastigote, trypomastigote and amastigote forms of T. cruzi, strain Y, suggesting cell death by necrosis with involvement of reactive oxygen species. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of COPD in the UK primary-care setting: an analysis of real-life prescribing patterns

PubMed Central

Price, David; West, Daniel; Brusselle, Guy; Gruffydd-Jones, Kevin; Jones, Rupert; Miravitlles, Marc; Rossi, Andrea; Hutton, Catherine; Ashton, Valerie L; Stewart, Rebecca; Bichel, Katsiaryna

2014-01-01

Background Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations. This study evaluated the current management of patients with COPD using a large UK primary-care database. Methods This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database. Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis. Results A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD). The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset. Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively). ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B. Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS. Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS. A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10). Conclusion COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting. Some patients receive no treatment despite experiencing symptoms. Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history. Many patients on treatment continue to have symptoms. PMID:25210450

IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

PubMed Central

Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

2009-01-01

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

Recent Progress in Laboratory Astrophysics and Astrochemistry Achieved with the COSmIC Facility

NASA Technical Reports Server (NTRS)

Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

2017-01-01

We describe the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory. COSmIC stands for "Cosmic Simulation Chamber" and is dedicated to the study of neutral and ionized molecules and nanoparticles under the low temperature and high vacuum conditions that are required to simulate various space environments such as diffuse interstellar clouds, circumstellar outflows and planetary atmospheres. COSmIC integrates a variety of state-of-the-art instruments that allow recreating simulated space conditions to generate, process and monitor cosmic analogs in the laboratory. The COSmIC experimental setup is composed of a Pulsed Discharge Nozzle (PDN) expansion, that generates a plasma in the stream of a free supersonic jet expansion, coupled to high-sensitivity, complementary in situ diagnostics: cavity ring down spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection, and Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection. Recent results obtained using COSmIC will be highlighted. In particular, the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) and in monitoring, in the laboratory, the formation of circumstellar dust grains and planetary atmosphere aerosols from their gas-phase molecular precursors. Plans for future laboratory experiments on interstellar and planetary molecules and grains will also be addressed, as well as the implications of the studies underway for astronomical observations and past and future space mission data analysis.

Solving the 56Ni Puzzle of Magnetar-powered Broad-lined Type IC Supernovae

NASA Astrophysics Data System (ADS)

Wang, Ling-Jun; Han, Yan-Hui; Xu, Dong; Wang, Shan-Qin; Dai, Zi-Gao; Wu, Xue-Feng; Wei, Jian-Yan

2016-11-01

Broad-lined Type Ic supernovae (SNe Ic-BL) are of great importance because their association with long-duration gamma-ray bursts (LGRBs) holds the key to deciphering the central engine of LGRBs, which refrains from being unveiled despite decades of investigation. Among the two popularly hypothesized types of central engine, I.e., black holes and strongly magnetized neutron stars (magnetars), there is mounting evidence that the central engine of GRB-associated SNe (GRB-SNe) is rapidly rotating magnetars. Theoretical analysis also suggests that magnetars could be the central engine of SNe Ic-BL. What puzzled the researchers is the fact that light-curve modeling indicates that as much as 0.2{--}0.5 {M}⊙ of 56Ni was synthesized during the explosion of the SNe Ic-BL, which is unfortunately in direct conflict with current state-of-the-art understanding of magnetar-powered 56Ni synthesis. Here we propose a dynamic model of magnetar-powered SNe to take into account the acceleration of the ejecta by the magnetar, as well as the thermalization of the injected energy. Assuming that the SN kinetic energy comes exclusively from the magnetar acceleration, we find that although a major fraction of the rotational energy of the magnetar is to accelerate the SN ejecta, a tiny fraction of this energy deposited as thermal energy of the ejecta is enough to reduce the needed 56Ni to 0.06 M ⊙ for both SN 1997ef and SN 2007ru. We therefore suggest that magnetars could power SNe Ic-BL in aspects both of energetics and of 56Ni synthesis.

An integrated direct loop-mediated isothermal amplification microdevice incorporated with an immunochromatographic strip for bacteria detection in human whole blood and milk without a sample preparation step.

PubMed

Lee, Dohwan; Kim, Yong Tae; Lee, Jee Won; Kim, Do Hyun; Seo, Tae Seok

2016-05-15

We have developed an integrated direct loop-mediated isothermal amplification (Direct LAMP) microdevice incorporated with an immunochromatographic strip (ICS) to identify bacteria contaminated in real samples. The Direct LAMP is a novel isothermal DNA amplification technique which does not require thermal cycling steps as well as any sample preparation steps such as cell lysis and DNA extraction for amplifying specific target genes. In addition, the resultant amplicons were colorimetrically detected on the ICS, thereby enabling the entire genetic analysis process to be simplified. The two functional units (Direct LAMP and ICS) were integrated on a single device without use of the tedious and complicated microvalve and tubing systems. The utilization of a slidable plate allows us to manipulate the fluidic control in the microchannels manually and the sequential operation of the Direct LAMP and ICS detection could be performed by switching the slidable plate to each functional unit. Thus, the combination of the direct isothermal amplification without any sample preparation and thermal cycling steps, the ICS based amplicon detection by naked eyes, and the slidable plate to eliminate the microvalves in the integrated microdevice would be an ideal platform for point-of-care DNA diaganotics. On the integrated Direct LAMP-ICS microdevice, we could analyze Staphylococcus aureus (S. aureus) and Escherichia coli O157:H7 (E. coli O157:H7) contaminated in human whole blood or milk at a single-cell level within 1h. Copyright © 2015 Elsevier B.V. All rights reserved.

The Elephant Trunk Nebula and the Trumpler 37 cluster: contribution of triggered star formation to the total population of an H II region

NASA Astrophysics Data System (ADS)

Getman, Konstantin V.; Feigelson, Eric D.; Sicilia-Aguilar, Aurora; Broos, Patrick S.; Kuhn, Michael A.; Garmire, Gordon P.

2012-11-01

Rich young stellar clusters produce H ii regions whose expansion into the nearby molecular cloud is thought to trigger the formation of new stars. However, the importance of this mode of star formation is uncertain. This investigation seeks to quantify triggered star formation (TSF) in IC 1396A (aka the Elephant Trunk Nebula), a bright-rimmed cloud (BRC) on the periphery of the nearby giant H ii region IC 1396 produced by the Trumpler 37 cluster. X-ray selection of young stars from Chandra X-ray Observatory data is combined with existing optical and infrared surveys to give a more complete census of the TSF population. Over 250 young stars in and around IC 1396A are identified; this doubles the previously known population. A spatio-temporal gradient of stars from the IC 1396A cloud towards the primary ionizing star HD 206267 is found. We argue that the TSF mechanism in IC 1396A is a radiation-driven implosion process persisting over several million years. Analysis of the X-ray luminosity and initial mass functions indicates that >140 stars down to 0.1 M⊙ were formed by TSF. Considering other BRCs in the IC 1396 H ii region, we estimate the TSF contribution for the entire H ii region exceeds 14-25 per cent today, and may be higher over the lifetime of the H ii region. Such triggering on the periphery of H ii regions may be a significant mode of star formation in the Galaxy.

Bladder Pain Syndrome/Interstitial Cystitis Is Associated with Hyperthyroidism

PubMed Central

Liu, Shih-Ping; Lin, Ching-Chun; Lin, Herng-Ching

2013-01-01

Background Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC) is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan. Design Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR) for having previously been diagnosed with hyperthyroidism between cases and controls. Results Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, p<0.001). The conditional logistic regression analysis revealed that compared to controls, the OR for prior hyperthyroidism among cases was 2.16 (95% confidence interval (CI): 1.27∼3.66). Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53) compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Conclusions Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population. PMID:23991081

Establishment of an intermittent cold stress model using Tupaia belangeri and evaluation of compound C737 targeting neuron-restrictive silencer factor

PubMed Central

Hai-Ying, Chi; Nagano, Kiori; Ezzikouri, Sayeh; Yamaguchi, Chiho; Kayesh, Mohammad Enamul Hoque; Rebbani, Khadija; Kitab, Bouchra; Nakano, Hirohumi; Kouji, Hiroyuki; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

2016-01-01

Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins. Based on these similarities, we hypothesized that induction of ICS in Tupaia would provide a useful animal model of stress responses. We exposed young adult Tupaia to ICS and observed decreases in body temperature and body weight in both female and male Tupaia, suggesting that Tupaia are an appropriate animal model for ICS studies. We further examined the efficacy of a new small-molecule compound, C737, against the effects of ICS. C737 mimics the helical structure of neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of target genes involved in neuronal function and pain modulation. Treatment with C737 significantly reduced stress-induced weight loss in female Tupaia; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that Tupaia represents a useful non-rodent ICS model. Our data also provide new insights into the function of NRSF/REST in stress-induced depression and other disorders with epigenetic influences or those with high prevalence in women. PMID:27041457

Analysis of a Statistical Relationship Between Dose and Error Tallies in Semiconductor Digital Integrated Circuits for Application to Radiation Monitoring Over a Wireless Sensor Network

NASA Astrophysics Data System (ADS)

Colins, Karen; Li, Liqian; Liu, Yu

2017-05-01

Mass production of widely used semiconductor digital integrated circuits (ICs) has lowered unit costs to the level of ordinary daily consumables of a few dollars. It is therefore reasonable to contemplate the idea of an engineered system that consumes unshielded low-cost ICs for the purpose of measuring gamma radiation dose. Underlying the idea is the premise of a measurable correlation between an observable property of ICs and radiation dose. Accumulation of radiation-damage-induced state changes or error events is such a property. If correct, the premise could make possible low-cost wide-area radiation dose measurement systems, instantiated as wireless sensor networks (WSNs) with unshielded consumable ICs as nodes, communicating error events to a remote base station. The premise has been investigated quantitatively for the first time in laboratory experiments and related analyses performed at the Canadian Nuclear Laboratories. State changes or error events were recorded in real time during irradiation of samples of ICs of different types in a 60Co gamma cell. From the error-event sequences, empirical distribution functions of dose were generated. The distribution functions were inverted and probabilities scaled by total error events, to yield plots of the relationship between dose and error tallies. Positive correlation was observed, and discrete functional dependence of dose quantiles on error tallies was measured, demonstrating the correctness of the premise. The idea of an engineered system that consumes unshielded low-cost ICs in a WSN, for the purpose of measuring gamma radiation dose over wide areas, is therefore tenable.

Relationship between Salmonella infection, shedding and serology in fattening pigs in low-moderate prevalence areas.

PubMed

San Román, B; Garrido, V; Sánchez, S; Martínez-Ballesteros, I; Garaizar, J; Mainar-Jaime, R C; Migura-Garcia, L; Grilló, M J

2018-04-27

Salmonella is a major foodborne pathogen causing important zoonosis worldwide. Pigs asymptomatically infected in mesenteric lymph nodes (MLN) can be intermittent shedders of the pathogen through faeces, being considered a major source of human infections. European baseline studies of fattening pig salmonellosis are based on Salmonella detection in MLN. This work studies the relationship between Salmonella infection in MLN and intestinal content (IC) shedding at slaughter and the relationship between the presence of the pathogen and the serologic status at farm level. Mean Salmonella prevalence in the selected pigs (vertically integrated production system of Navarra, Spain) was 7.2% in MLN, 8.4% in IC and 9.6% in serum samples. In this low-moderate prevalence context, poor concordance was found between MLN infection and shedding at slaughter and between bacteriology and serology. In fact, most of shedders were found uninfected in MLN (83%) or carrying different Salmonella strains in MLN and in IC (90%). The most prevalent Salmonellae were Typhimurium resistant to ACSSuT ± Nx or ASSuT antibiotic families, more frequently found invading the MLN (70%) than in IC (33.9%). Multivariable analysis revealed that risk factors associated with the presence of Salmonella in MLN or in IC were different, mainly related either to good hygiene practices or to water and feed control, respectively. Overall, in this prevalence context, detection of Salmonella in MLN is an unreliable predictor of faecal shedding at abattoir, indicating that subclinical infections in fattening pigs MLN could have limited relevance in the IC shedding. © 2018 Blackwell Verlag GmbH.

Biological effects of low-dose ionizing radiation exposure on interventional cardiologists.

PubMed

Zakeri, F; Hirobe, T; Akbari Noghabi, K

2010-09-01

Interventional cardiologists (ICs) are likely to receive high radiation exposure as a result of procedures they undertake. To assess the effects of low-dose X-ray radiation exposure on chromosomal damage and on selected indices of cellular and humoral immunity in ICs. The study population consisted of 37 ICs and 37 clinical physicians as the control group with similar age, sex and duration of employment, without any work-related exposure to ionizing radiation. Cytogenetic studies were performed by chromosome aberration analysis and immunological studies by flow cytometry, enzyme-linked immunosorbent assay and immunodiffusion techniques. The frequencies of aberrant cells, chromosome breaks and dicentrics plus centric rings were significantly higher in the exposed group compared to the control group (P < 0.05; P < 0.01; P < 0.001, respectively), without positive correlation between the frequency of dicentric and centric ring aberrations and the cumulative doses of the ICs (r = 0.24, not significant). A significant increase was observed in the expression of activation marker CD69 on TCD4(+) stimulated cells in serum immunoglobulin G and interleukin (IL)-2 (P < 0.05) and a significant decrease in serum IL-10 (P < 0.05) in the ICs compared with that of the control group. There was no statistical difference between the two groups in terms of number of white blood cells and lymphocytes, CD3(+), CD4(+) and CD8(+) T cells, CD19(+) and CD16(+) 56(+) cells and concentrations of interferon (IFN)-gamma, IL-4, IL-6 and IL-8 cytokines. While cytogenetic results show higher chromosomal damage, some immune responses are stimulated or modulated immunologically in ICs.

Effects of skin-to-skin contact on autonomic pain responses in preterm infants.

PubMed

Cong, Xiaomei; Cusson, Regina M; Walsh, Stephen; Hussain, Naveed; Ludington-Hoe, Susan M; Zhang, Di

2012-07-01

The purpose of this randomized crossover trial was to determine the effects on autonomic responses in preterm infants of longer Kangaroo Care (30 minutes, KC30) and shorter KC (15 minutes, KC15) before and throughout heel stick compared with incubator care (IC). Beat-to-beat heart rate (HR) and spectral power analysis of heart rate variability, low frequency power (LF), high frequency power (HF), and LF/HF ratio were measured in 26 infants. HR changes from Baseline to Heel Stick were significantly less in KC30 and KC15 than in IC, and more infants had HR decrease in IC than in 2 KC conditions. In IC, LF and HF significantly increased from Baseline to Heel Stick and dropped from Heel Stick to Recovery; in 2 KC conditions, no changes across study phases were found. During Heel Stick, LF and HF were significantly higher in IC than in KC30. In all 3 conditions, LF/HF ratio decreased from Baseline to Heel Stick and increased to Recovery; no differences were found between IC and two KC conditions. Both longer and shorter KC before and throughout heel stick can stabilize HR response in preterm infants, and longer KC significantly affected infants' sympathetic and parasympathetic responses during heel stick compared with incubator care. This study showed that KC has a significant effect on reducing autonomic pain responses in preterm infants. The findings support that KC is a safe and effective pain intervention in the neonatal intensive care unit. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

Bladder pain syndrome/interstitial cystitis is associated with hyperthyroidism.

PubMed

Chung, Shiu-Dong; Liu, Shih-Ping; Lin, Ching-Chun; Li, Hsien-Chang; Lin, Herng-Ching

2013-01-01

Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC) is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan. Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR) for having previously been diagnosed with hyperthyroidism between cases and controls. Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, p<0.001). The conditional logistic regression analysis revealed that compared to controls, the OR for prior hyperthyroidism among cases was 2.16 (95% confidence interval (CI): 1.27∼3.66). Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53) compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population.

COSTS OF INTERSTITAL CYSTITIS IN A MANAGED CARE POPULATION

PubMed Central

Clemens, J. Quentin; Meenan, Richard T.; O’Keeffe Rosetti, Maureen C.; Kimes, Terry; Calhoun, Elizabeth A.

2008-01-01

Objective This study assessed the direct medical costs, medication and procedure use associated with interstitial cystitis (IC) in women in the Kaiser Permanente Northwest (KPNW) managed care population. Methods The KPNW electronic medical record was utilized to identify women diagnosed with interstitial cystitis (n=239). Each of these cases was matched with three controls based on age and duration in the health plan. Health plan cost accounting data were used to determine inpatient, outpatient, and pharmacy costs for 1998-2003. An analysis of prescription medication use, cystoscopic and urodynamic procedures commonly associated with IC was also performed. To evaluate for comorbidities, an automated risk-adjustment model (RxRisk) linked to 28 chronic medical conditions was applied to the administrative datasets from both groups. Results The mean duration from the date of IC diagnosis to the end of the study period was 36.6 months (range 1.4-60). Mean yearly costs were 2.4-fold greater in cases than controls ($7100 vs. $2994), and median yearly costs were 3.8-fold greater ($5000 vs. $1304). These cost differences were predominantly due to outpatient and pharmacy expenses. Medication and procedure use were significantly greater in cases than controls. These findings were consistent across RxRisk categories, which suggest that the observed cost differences are IC-specific. Conclusions The direct per-person costs of IC are high, with average yearly costs approximately $4000 greater than age-matched controls. This cost differential is an underestimate, as costs preceding the diagnosis, use of alternative therapies, indirect costs and costs of those with IC that is not diagnosed are not included. PMID:18329077