Failure of PCR to Detect Treponema pallidum ssp. pertenue DNA in Blood in Latent Yaws.

PubMed

Marks, Michael; Katz, Samantha; Chi, Kai-Hua; Vahi, Ventis; Sun, Yongcheng; Mabey, David C; Solomon, Anthony W; Chen, Cheng Y; Pillay, Allan

2015-01-01

Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA) and Rapid Plasma Reagin (RPR) tests and 7 controls (negative serology), all collected as part of a prospective study of yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active yaws whilst 128 were considered to have latent yaws. 43 children had high titre rapid plasma reagins (RPRs) of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in yaws than in syphilis. As the goal of the yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool.

Failure of PCR to Detect Treponema pallidum ssp. pertenue DNA in Blood in Latent Yaws

PubMed Central

Chi, Kai-Hua; Vahi, Ventis; Sun, Yongcheng; Mabey, David C.; Solomon, Anthony W.; Chen, Cheng Y.; Pillay, Allan

2015-01-01

Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA) and Rapid Plasma Reagin (RPR) tests and 7 controls (negative serology), all collected as part of a prospective study of yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active yaws whilst 128 were considered to have latent yaws. 43 children had high titre rapid plasma reagins (RPRs) of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in yaws than in syphilis. As the goal of the yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool. PMID:26125585

Over-the-road testing of the instrumented tank car : a load environment study.

DOT National Transportation Integrated Search

2010-05-01

Fractures have been observed on stub sill tank cars for many years. Undetected and unattended, these fractures can develop into a variety of tank car failures. While tank car ruptures are relatively rare, the potential for a catastrophic HAZMAT relea...

The length of an internal poly(A) tract of hibiscus latent Singapore virus is crucial for its replication.

PubMed

Niu, Shengniao; Cao, Shishu; Huang, Li-Jing; Tan, Kelvin Chee-Leong; Wong, Sek-Man

2015-01-01

Hibiscus latent Singapore virus (HLSV) mutants were constructed to study roles of its internal poly(A) tract (IPAT) in viral replication and coat protein (CP) expression. Shortening of the IPAT resulted in reduced HLSV RNA accumulation and its minimal length required for HLSV CP expression in plants was 24 nt. Disruption of a putative long range RNA-RNA interacting structure between 5' and 3' untranslated regions of HLSV-22A and -24A resulted in reduced viral RNA and undetectable CP accumulation in inoculated leaves. Replacement of the IPAT in HLSV with an upstream pseudoknot domain (UPD) of Tobacco mosaic virus (TMV) or insertion of the UPD to the immediate downstream of a 24 nt IPAT in HLSV resulted in drastically reduced viral RNA replication. Plants infected with a TMV mutant by replacement of the UPD with 43 nt IPAT exhibited milder mosaic symptoms without necrosis. We have proposed a model for HLSV replication. Copyright © 2014 Elsevier Inc. All rights reserved.

Syphilis in the AIDS era: diagnostic dilemma and therapeutic challenge.

PubMed

Scythes, John B; Jones, Colman M

2013-06-01

This review argues that syphilis has been underdiagnosed and undertreated, a problem that goes back to the beginning of the Wassermann era, and indeed long before. Non-treponemal tests do not detect the larger pool of persons with latent syphilis, the immunological consequences of which have not been systematically investigated in the context of HIV infection and progression to AIDS. Recent efforts to confirm the prevalence of syphilis in high-risk patients by reverse sequence screening, i.e. using a treponemal test first, as the screening test, have revealed untreated syphilis at higher rates than expected. Further testing using PCR discovered even more previously undetected cases. We suggest that latent syphilis is a chronic active immunological condition that drives the AIDS process and cannot be managed with the older Wassermann-based algorithm, and that non-treponemal tests have failed to associate syphilis with immune suppression since this screening concept was developed in 1906. In light of the overwhelming association between a past history of syphilis and HIV seroconversion, more sensitive tools, including recombinant antigen-based immunological tests and direct detection (PCR) technology, are needed to adequately assess the role of latent syphilis in persons with HIV/AIDS. Repeating older syphilis reinoculation studies may help establish a successful animal model for AIDS, and resolve many paradoxes in HIV science.

Delay-Induced Attenuation of Latent Inhibition with a Conditioned Emotional Response Depends on CS-US Strength

ERIC Educational Resources Information Center

De la Casa, Luis G.; Diaz, Estrella; Lubow, R.E.

2005-01-01

Latent Inhibition (LI) attenuation when a long delay is introduced between acquisition and test phases has been repeatedly observed using aversive conditioning procedures (e.g., Aguado, Symonds, & Hall, 1994). This effect has been used as evidence to support those theories that consider LI to be the result of a retrieval failure. We designed three…

Food deprivation enhances both autoshaping and autoshaping impairment by a latent inhibition procedure.

PubMed

Sparber, S B; Bollweg, G L; Messing, R B

1991-02-01

The influence of food deprivation on acquisition of autoshaped operant behavior was measured. In one study separate groups of young, male rats that were deprived to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping procedure in which a 6 s delay was interposed between lever retraction (which occurred when rats made a lever touch, or automatically after 15 s) and food pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of ad lib weight prior to testing in a latent inhibition variation of the same autoshaping procedure. This was done to determine if greater food deprivation would enhance learning which, because of the latent inhibition manipulation, is manifest as less lever-directed behavior. Greater food deprivation was associated both with fast acquisition of autoshaped lever responding and with more reliable failure to increase lever responding in the latent inhibition paradigm. Thus, increasing food deprivation was associated with enhanced acquisition regardless of whether the required performance was an increase or a failure to increase the same behavior, indicating a specific effect on learning. Copyright © 1991. Published by Elsevier B.V.

Latent Subgroup Analysis of a Randomized Clinical Trial Through a Semiparametric Accelerated Failure Time Mixture Model

PubMed Central

Altstein, L.; Li, G.

2012-01-01

Summary This paper studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time-to-event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all-or-none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley-James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma. PMID:23383608

Factors That Affect Software Testability

NASA Technical Reports Server (NTRS)

Voas, Jeffrey M.

1991-01-01

Software faults that infrequently affect software's output are dangerous. When a software fault causes frequent software failures, testing is likely to reveal the fault before the software is releases; when the fault remains undetected during testing, it can cause disaster after the software is installed. A technique for predicting whether a particular piece of software is likely to reveal faults within itself during testing is found in [Voas91b]. A piece of software that is likely to reveal faults within itself during testing is said to have high testability. A piece of software that is not likely to reveal faults within itself during testing is said to have low testability. It is preferable to design software with higher testabilities from the outset, i.e., create software with as high of a degree of testability as possible to avoid the problems of having undetected faults that are associated with low testability. Information loss is a phenomenon that occurs during program execution that increases the likelihood that a fault will remain undetected. In this paper, I identify two brad classes of information loss, define them, and suggest ways of predicting the potential for information loss to occur. We do this in order to decrease the likelihood that faults will remain undetected during testing.

Recent developments in the effort to cure HIV infection: going beyond N = 1.

PubMed

Siliciano, Janet D; Siliciano, Robert F

2016-02-01

Combination antiretroviral therapy (ART) can suppress plasma HIV to undetectable levels, allowing HIV-infected individuals who are treated early a nearly normal life span. Despite the clear ability of ART to prevent morbidity and mortality, it is not curative. Even in individuals who have full suppression of viral replication on ART, there are resting memory CD4+ T cells that harbor stably integrated HIV genomes, which are capable of producing infectious virus upon T cell activation. This latent viral reservoir is considered the primary obstacle to the development of an HIV cure, and recent efforts in multiple areas of HIV research have been brought to bear on the development of strategies to eradicate or develop a functional cure for HIV. Reviews in this series detail progress in our understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies.

Risk analysis by FMEA as an element of analytical validation.

PubMed

van Leeuwen, J F; Nauta, M J; de Kaste, D; Odekerken-Rombouts, Y M C F; Oldenhof, M T; Vredenbregt, M J; Barends, D M

2009-12-05

We subjected a Near-Infrared (NIR) analytical procedure used for screening drugs on authenticity to a Failure Mode and Effects Analysis (FMEA), including technical risks as well as risks related to human failure. An FMEA team broke down the NIR analytical method into process steps and identified possible failure modes for each step. Each failure mode was ranked on estimated frequency of occurrence (O), probability that the failure would remain undetected later in the process (D) and severity (S), each on a scale of 1-10. Human errors turned out to be the most common cause of failure modes. Failure risks were calculated by Risk Priority Numbers (RPNs)=O x D x S. Failure modes with the highest RPN scores were subjected to corrective actions and the FMEA was repeated, showing reductions in RPN scores and resulting in improvement indices up to 5.0. We recommend risk analysis as an addition to the usual analytical validation, as the FMEA enabled us to detect previously unidentified risks.

Potential of airborne LiDAR data analysis to detect subtle landforms of slope failure: Portainé, Central Pyrenees

NASA Astrophysics Data System (ADS)

Ortuño, María; Guinau, Marta; Calvet, Jaume; Furdada, Glòria; Bordonau, Jaume; Ruiz, Antonio; Camafort, Miquel

2017-10-01

Slope failures have been traditionally detected by field inspection and aerial-photo interpretation. These approaches are generally insufficient to identify subtle landforms, especially those generated during the early stages of failures, and particularly where the site is located in forested and remote terrains. We present the identification and characterization of several large and medium size slope failures previously undetected within the Orri massif, Central Pyrenees. Around 130 scarps were interpreted as being part of Rock Slope Failures (RSFs), while other smaller and more superficial failures were interpreted as complex movements combining colluvium slow flow/slope creep and RSFs. Except for one of them, these slope failures had not been previously detected, albeit they extend across a 15% of the studied region. The failures were identified through the analysis of a high-resolution (1 m) LIDAR-derived bare earth Digital Elevation Model (DEM). Most of the scarps are undetectable either by fieldwork, photo interpretation or 5 m resolution topography analysis owing to their small heights (0.5 to 2 m) and their location within forest areas. In many cases, these landforms are not evident in the field due to the presence of other minor irregularities in the slope and the lack of open views due to the forest. 2D and 3D visualization of hillshade maps with different sun azimuths provided an overall picture of the scarp assemblage and permitted a more complete analysis of the geometry of the scarps with respect to the slope and the structural fabric. The sharpness of some of the landforms suggests ongoing activity, which should be explored in future detailed studies in order to assess potential hazards affecting the Portainé ski resort. Our results reveal that close analysis of the 1 m LIDAR-derived DEM can significantly help to detect early-stage slope deformations in high mountain regions, and that expert judgment of the DEM is essential when dealing with subtle landforms. The incorporation of this approach in regional mapping represents a great advance in completing the catalogue of slope failures and will eventually contribute to a better understanding of the spatial factors controlling them.

Li-ion Battery Separators, Mechanical Integrity and Failure Mechanisms Leading to Soft and Hard Internal Shorts

PubMed Central

Zhang, Xiaowei; Sahraei, Elham; Wang, Kai

2016-01-01

Separator integrity is an important factor in preventing internal short circuit in lithium-ion batteries. Local penetration tests (nail or conical punch) often produce presumably sporadic results, where in exactly similar cell and test set-ups one cell goes to thermal runaway while the other shows minimal reactions. We conducted an experimental study of the separators under mechanical loading, and discovered two distinct deformation and failure mechanisms, which could explain the difference in short circuit characteristics of otherwise similar tests. Additionally, by investigation of failure modes, we provided a hypothesis about the process of formation of local “soft short circuits” in cells with undetectable failure. Finally, we proposed a criterion for predicting onset of soft short from experimental data. PMID:27581185

Risk analysis of analytical validations by probabilistic modification of FMEA.

PubMed

Barends, D M; Oldenhof, M T; Vredenbregt, M J; Nauta, M J

2012-05-01

Risk analysis is a valuable addition to validation of an analytical chemistry process, enabling not only detecting technical risks, but also risks related to human failures. Failure Mode and Effect Analysis (FMEA) can be applied, using a categorical risk scoring of the occurrence, detection and severity of failure modes, and calculating the Risk Priority Number (RPN) to select failure modes for correction. We propose a probabilistic modification of FMEA, replacing the categorical scoring of occurrence and detection by their estimated relative frequency and maintaining the categorical scoring of severity. In an example, the results of traditional FMEA of a Near Infrared (NIR) analytical procedure used for the screening of suspected counterfeited tablets are re-interpretated by this probabilistic modification of FMEA. Using this probabilistic modification of FMEA, the frequency of occurrence of undetected failure mode(s) can be estimated quantitatively, for each individual failure mode, for a set of failure modes, and the full analytical procedure. Copyright © 2012 Elsevier B.V. All rights reserved.

Detailed investigation of causes of avionics field failures

NASA Astrophysics Data System (ADS)

Kallis, J. M.; Buechler, D. W.; Richardson, Z. C.; Backes, P. G.; Lopez, S. B.; Erickson, J. J.; van Westerhuyzen, D. H.

A detailed analysis of digital and analog modules from the F-15 AN/APG-63 Radar was performed to identify the kinds, types, and number of life models based on observed failure modes, mechanisms, locations, and characteristics needed to perform a Failure Free Operating Period prediction for these items. It is found that a significant fraction of the failures of the analog module and a small fraction of those of the digital module resulted from the exacerbation of latent defects by environmental stresses. It is also found that the fraction of failures resulting from thermal cycling and vibration is small.

A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats

PubMed Central

Marinaro, Mariarosaria; Rezza, Giovanni; Del Giudice, Giuseppe; Colao, Valeriana; Tarsitano, Elvira; Camero, Michele; Losurdo, Michele; Buonavoglia, Canio; Tempesta, Maria

2012-01-01

The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats. PMID:22511971

Utilizing the GentleWave® System for Debridement of Undetected Apical Anatomy.

PubMed

Ford, Michael W

2018-03-01

Debriding and disinfecting complex anatomies within the root canal system pose a major challenge during root canal therapy. Even with current chemomechanical techniques, debris and bacterial remnants are commonly left behind, which are generally believed to increase the risk of endodontic failure. This case details the use of a new technique to debride complex apical anatomy in a maxillary molar. A 48-year-old female presented to the clinic with a chief complaint of increasing pain in her tooth. Clinical examination of the right first maxillary molar (#3) revealed moderate sensitivity to percussion and mild sensitivity to palpation. A pulpal diagnosis of symptomatic irreversible pulpitis and a periapi-cal diagnosis of symptomatic apical periodontitis were made. Mechanical instrumentation was performed using rotary file size #25/.04 for the mesiobuccal and distobuccal canals and size #25/.06 for the palatal canal to create a fluid path and enable obturation of the root canal system following the GentleWave® Procedure. The GentleWave Procedure was completed using Multisonic Ultracleaning™ for complete debridement and disinfection of the root canal system. The tooth was obturated using a warm vertical continuous wave obturation technique. Postoperative radiographs revealed complex anatomy within the apical third that was undetected both during pre-operative radiography and mechanical instrumentation. The palatal canal exhibited a complex apical delta with multiple points of exit, and the mesiobuccal canal revealed an undetected lateral canal within the apical third that had a separate and distinct egress. Conclusion and clinical significance: It is important for the clinician to debride and disinfect complex anatomy within the root canal system to reduce the risk of endodontic failure. This case report highlights the clinical significance of utilizing the GentleWave Procedure for detecting complex apical anatomy during endodontic therapy.

The Effects of Coach Training on Fear of Failure in Youth Swimmers: A Latent Growth Curve Analysis from a Randomized, Controlled Trial

ERIC Educational Resources Information Center

Conroy, David E.; Coatsworth, Douglas J.

2004-01-01

The present study was a randomized trial of the efficacy of psychosocial and injury prevention-based coach training programs for reducing fear of failure (FF) among youth swimmers aged 7 to 18 years. Results revealed that (a) psychosocial training increased coaches' use of reward/reinforcement, (b) the FF measure demonstrated strong factorial…

Modeling HIV Cure

NASA Astrophysics Data System (ADS)

Perelson, Alan; Conway, Jessica; Cao, Youfang

A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of post-treatment control (PTC) or ``functional cure'' of HIV-infection. Some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection such that the amount of virus in the circulation is maintained undetectable by clinical assays for years. The model explains PTC occurring in some patients by having a parameter regime in which the model exhibits bistability, with both a low and high steady state viral load being stable. The model makes a number of predictions about how to attain the low PTC steady state. Bistability in this model depends upon the immune response becoming exhausted when over stimulated. I will also present a generalization of the model in which immunotherapy can be used to reverse immune exhaustion and compare model predictions with experiments in SIV infected macaques given immunotherapy and then taken off of antiretroviral therapy. Lastly, if time permits, I will discuss one of the hurdles to true HIV eradication, latently infected cells, and present clinical trial data and a new model addressing pharmacological means of flushing out the latent reservoir. Supported by NIH Grants AI028433 and OD011095.

Interpretational confounding is due to misspecification, not to type of indicator: comment on Howell, Breivik, and Wilcox (2007).

PubMed

Bollen, Kenneth A

2007-06-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.

Guidance and Control Design Considerations for Low-Altitude and Terminal-Area Flight

DTIC Science & Technology

1978-04-01

MEAN TIME BETWEEN DEFECTS MEAN TIME BETWEEN UNDETECTED FAILURES 1 BASIC SYSTEM 49. S hrs 8, 213 hrs 2 DUPLEX TFC/ APFD 51.0 hrs 14. 981 hrs 3 2...MOTION SENSORS Figure 6 TF System 2 AERIAL RADAR TX/RX R.P SERVOS STRAP DOWN INS «EL.VG hi I 1 -i «JNAV/WASS I J TF/ APFD COMPUTER

Semiparametric regression analysis of failure time data with dependent interval censoring.

PubMed

Chen, Chyong-Mei; Shen, Pao-Sheng

2017-09-20

Interval-censored failure-time data arise when subjects are examined or observed periodically such that the failure time of interest is not examined exactly but only known to be bracketed between two adjacent observation times. The commonly used approaches assume that the examination times and the failure time are independent or conditionally independent given covariates. In many practical applications, patients who are already in poor health or have a weak immune system before treatment usually tend to visit physicians more often after treatment than those with better health or immune system. In this situation, the visiting rate is positively correlated with the risk of failure due to the health status, which results in dependent interval-censored data. While some measurable factors affecting health status such as age, gender, and physical symptom can be included in the covariates, some health-related latent variables cannot be observed or measured. To deal with dependent interval censoring involving unobserved latent variable, we characterize the visiting/examination process as recurrent event process and propose a joint frailty model to account for the association of the failure time and visiting process. A shared gamma frailty is incorporated into the Cox model and proportional intensity model for the failure time and visiting process, respectively, in a multiplicative way. We propose a semiparametric maximum likelihood approach for estimating model parameters and show the asymptotic properties, including consistency and weak convergence. Extensive simulation studies are conducted and a data set of bladder cancer is analyzed for illustrative purposes. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

ISS Fiber Optic Failure Investigation Root Cause Report

NASA Technical Reports Server (NTRS)

Leidecker, Henning; Plante, Jeannette

2000-01-01

In August of 1999, Boeing Corporation (Boeing) engineers began investigating failures of optical fiber being used on International Space Station flight hardware. Catastrophic failures of the fiber were linked to a defect in the glass fiber. Following several meetings of Boeing and NASA engineers and managers, Boeing created and led an investigation team, which examined the reliability of the cable installed in the U.S. Lab. NASA Goddard Space Flight Center's Components Technologies and Radiation Effects Branch (GSFC) led a team investigating the root cause of the failures. Information was gathered from: regular telecons and other communications with the investigation team, investigative trips to the cable distributor's plant, the cable manufacturing plant and the fiber manufacturing plant (including a review of build records), destructive and non-destructive testing, and expertise supplied by scientists from Dupont, and Lucent-Bell Laboratories. Several theories were established early on which were not able to completely address the destructive physical analysis and experiential evidence. Lucent suggested hydrofluoric acid (HF) etching of the glass and successfully duplicated the "rocket engine" defect. Strength testing coupled with examination of the low strength break sites linked features in the polyimide coating with latent defect sites. The information provided below explains what was learned about the susceptibility of the pre-cabled fiber to failure when cabled as it was for Space Station and the nature of the latent defects.

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

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

Zheng, Yuanshui, E-mail: yuanshui.zheng@okc.procure.com; Johnson, Randall; Larson, Gary

Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authorsmore » estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.« less

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis.

PubMed

Zheng, Yuanshui; Johnson, Randall; Larson, Gary

2016-06-01

Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.

Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

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

Iordanskiy, Sergey; Van Duyne, Rachel; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702

The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lowermore » doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation (IR) increases HIV-1 transcription in latently-infected cells. • IR enhances activating effect of bryostatin 1 on HIV-1 transcription in monocytes. • IR induces apoptosis in HIV-1 infected cells via phosphorylation of p53 Ser46. • IR of HIV-1 infected humanized mice increases HIV-1 RNA in plasma, lung and brain.« less

Retrospectively Estimating Prevalence of Peanut Allergy Genetic Markers in an Air Force Population

DTIC Science & Technology

2018-01-25

operational success. Latent food allergies could manifest catastrophic outcomes during missions, resulting in potential failure and loss of life ...Understanding an individual’s risk of developing severe allergies is one of many components that can make up a high- quality surveillance and public health...food allergies could manifest catastrophic outcomes during missions, resulting in potential failure and loss of life . Understanding an individual’s

Failure detection and fault management techniques for flush airdata sensing systems

NASA Technical Reports Server (NTRS)

Whitmore, Stephen A.; Moes, Timothy R.; Leondes, Cornelius T.

1992-01-01

A high-angle-of-attack flush airdata sensing system was installed and flight tested on the F-18 High Alpha Research Vehicle at NASA-Dryden. This system uses a matrix of pressure orifices arranged in concentric circles on the nose of the vehicle to determine angles of attack, angles of sideslip, dynamic pressure, and static pressure as well as other airdata parameters. Results presented use an arrangement of 11 symmetrically distributed ports on the aircraft nose. Experience with this sensing system data indicates that the primary concern for real-time implementation is the detection and management of overall system and individual pressure sensor failures. The multiple port sensing system is more tolerant to small disturbances in the measured pressure data than conventional probe-based intrusive airdata systems. However, under adverse circumstances, large undetected failures in individual pressure ports can result in algorithm divergence and catastrophic failure of the entire system. How system and individual port failures may be detected using chi sq. analysis is shown. Once identified, the effects of failures are eliminated using weighted least squares.

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

PubMed

Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

2017-08-15

A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV/SIV-infected macrophages persist despite ART. Markers of macrophage activation and neuronal damage are observed in the CSF of HIV-infected individuals and of SIV-infected macaques on suppressive ART regimens, suggesting that the CNS has continued virus infection and latent infection. A controversy exists as to whether brain macrophages represent a latent source of replication-competent virus capable of reestablishing infection upon treatment interruption. In this study, we demonstrated the presence of the latent macrophage reservoir in brains of SIV-infected ART-treated macaques and analyzed the reservoir using our established outgrowth assay to quantitate macrophages harboring replication-competent SIV genomes. Our results support the idea of the existence of other latent reservoirs in addition to resting CD4 + T cells and underscore the importance of macrophages in developing strategies to eradicate HIV. Copyright © 2017 Avalos et al.

Damage tolerance in filament-wound graphite/epoxy pressure vessels

NASA Technical Reports Server (NTRS)

Simon, William E.; Ngueyen, Vinh D.; Chenna, Ravi K.

1995-01-01

Graphite/epoxy composites are extensively used in the aerospace and sporting goods industries due to their superior engineering properties compared to those of metals. However, graphite/epoxy is extremely susceptible to impact damage which can cause considerable and sometimes undetected reduction in strength. An inelastic impact model was developed to predict damage due to low-velocity impact. A transient dynamic finite element formulation was used in conjunction with the 3D Tsai-Wu failure criterion to determine and incorporate failure in the materials during impact. Material degradation can be adjusted from no degradation to partial degradation to full degradation. The developed software is based on an object-oriented implementation framework called Extensible Implementation Framework for Finite Elements (EIFFE).

Decomposition-Based Failure Mode Identification Method for Risk-Free Design of Large Systems

NASA Technical Reports Server (NTRS)

Tumer, Irem Y.; Stone, Robert B.; Roberts, Rory A.; Clancy, Daniel (Technical Monitor)

2002-01-01

When designing products, it is crucial to assure failure and risk-free operation in the intended operating environment. Failures are typically studied and eliminated as much as possible during the early stages of design. The few failures that go undetected result in unacceptable damage and losses in high-risk applications where public safety is of concern. Published NASA and NTSB accident reports point to a variety of components identified as sources of failures in the reported cases. In previous work, data from these reports were processed and placed in matrix form for all the system components and failure modes encountered, and then manipulated using matrix methods to determine similarities between the different components and failure modes. In this paper, these matrices are represented in the form of a linear combination of failures modes, mathematically formed using Principal Components Analysis (PCA) decomposition. The PCA decomposition results in a low-dimensionality representation of all failure modes and components of interest, represented in a transformed coordinate system. Such a representation opens the way for efficient pattern analysis and prediction of failure modes with highest potential risks on the final product, rather than making decisions based on the large space of component and failure mode data. The mathematics of the proposed method are explained first using a simple example problem. The method is then applied to component failure data gathered from helicopter, accident reports to demonstrate its potential.

Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

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

Hammel, Markus; Michel, Geert; Hoefer, Christina

2007-08-10

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies inmore » type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.« less

78 FR 6247 - Airworthiness Directives; the Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... Company Model 757 airplanes. The existing AD currently requires revising the maintenance program by... for ignition sources inside fuel tanks caused by latent failures, alterations, repairs, or maintenance... CONTACT: Kevin Nguyen, Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, Seattle Aircraft...

76 FR 19710 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

...: No person may operate an aircraft for which a manufacturer's maintenance manual or instructions for... by latent failures, alterations, repairs, or maintenance actions, which, in combination with... CONTACT: Tak Kobayashi, Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, Seattle Aircraft...

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Investigation of accelerated stress factors and failure/degradation mechanisms in terrestrial solar cells

NASA Technical Reports Server (NTRS)

Lathrop, J. W.

1983-01-01

Results of an ongoing research program into the reliability of terrestrial solar cells are presented. Laboratory accelerated testing procedures are used to identify failure/degradation modes which are then related to basic physical, chemical, and metallurgical phenomena. In the most recent tests, ten different types of production cells, both with and without encapsulation, from eight different manufacturers were subjected to a variety of accelerated tests. Results indicated the presence of a number of hitherto undetected failure mechanisms, including Schottky barrier formation at back contacts and loss of adhesion of grid metallization. The mechanism of Schottky barrier formation is explained by hydrogen, formed by the dissociation of water molecules at the contact surface, diffusing to the metal semiconductor interface. This same mechanism accounts for the surprising increase in sensitivity to accelerated stress conditions that was observed in some cells when encapsulated.

Study of SEM induced current and voltage contrast modes to assess semiconductor reliability

NASA Technical Reports Server (NTRS)

Beall, J. R.

1976-01-01

The purpose of the scanning electron microscopy study was to review the failure history of existing integrated circuit technologies to identify predominant failure mechanisms, and to evaluate the feasibility of their detection using SEM application techniques. The study investigated the effects of E-beam irradiation damage and contamination deposition rates; developed the necessary methods for applying the techniques to the detection of latent defects and weaknesses in integrated circuits; and made recommendations for applying the techniques.

Exploring MEDLINE Space with Random Indexing and Pathfinder Networks

PubMed Central

Cohen, Trevor

2008-01-01

The integration of disparate research domains is a prerequisite for the success of the translational science initiative. MEDLINE abstracts contain content from a broad range of disciplines, presenting an opportunity for the development of methods able to integrate the knowledge they contain. Latent Semantic Analysis (LSA) and related methods learn human-like associations between terms from unannotated text. However, their computational and memory demands limits their ability to address a corpus of this size. Furthermore, visualization methods previously used in conjunction with LSA have limited ability to define the local structure of the associative networks LSA learns. This paper explores these issues by (1) processing the entire MEDLINE corpus using Random Indexing, a variant of LSA, and (2) exploring learned associations using Pathfinder Networks. Meaningful associations are inferred from MEDLINE, including a drug-disease association undetected by PUBMED search. PMID:18999236

Exploring MEDLINE space with random indexing and pathfinder networks.

PubMed

Cohen, Trevor

2008-11-06

The integration of disparate research domains is a prerequisite for the success of the translational science initiative. MEDLINE abstracts contain content from a broad range of disciplines, presenting an opportunity for the development of methods able to integrate the knowledge they contain. Latent Semantic Analysis (LSA) and related methods learn human-like associations between terms from unannotated text. However, their computational and memory demands limits their ability to address a corpus of this size. Furthermore, visualization methods previously used in conjunction with LSA have limited ability to define the local structure of the associative networks LSA learns. This paper explores these issues by (1) processing the entire MEDLINE corpus using Random Indexing, a variant of LSA, and (2) exploring learned associations using Pathfinder Networks. Meaningful associations are inferred from MEDLINE, including a drug-disease association undetected by PUBMED search.

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Crucian, Brian; Pierson, Duane L.; Sams, Clarence; Stowe, Raymond P.

2007-01-01

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 degrees head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity (AG) as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system, and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of Epstein barr virus (EBV), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 106 PBMCs. Overall, these data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

NASA Technical Reports Server (NTRS)

Mehta, Satish; Crusian, Brian; Pierson, Duane; Sams, Clarence; Stowe, Raymond

2007-01-01

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 deg. head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of EBV and CMV was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in plasma cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 10(exp 6) PBMCs. These data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir

PubMed Central

Avalos, Claudia R.; Abreu, Celina M.; Queen, Suzanne E.; Li, Ming; Price, Sarah; Shirk, Erin N.; Engle, Elizabeth L.; Forsyth, Ellen; Bullock, Brandon T.; Mac Gabhann, Feilim; Wietgrefe, Stephen W.; Haase, Ashley T.; Zink, M. Christine; Mankowski, Joseph L.; Clements, Janice E.

2017-01-01

ABSTRACT A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. PMID:28811349

Factors associated with therapeutic success in HIV-positive individuals in southern Brazil.

PubMed

Silveira, M P T; Maurer, P; Guttier, M C; Moreira, L B

2015-04-01

Therapeutic success is characterized by undetectable viral load, immune reconstitution confirmed by CD4+ T-cell count and no clinical manifestations of disease. High treatment adherence is a major determinant of therapeutic success that needs prevention of viral replication, allowing immune reconstitution. Adherence to treatment <95% has been associated with both immune and viral failure. The objective of this study was to evaluate factors associated with therapeutic success in adult patients on highly active antiretroviral therapy (HAART) in a specialized centre for HIV-AIDS in southern Brazil, being defined therapeutic success as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥ 95%. We conducted a historical cohort study nested in the PC-HIV randomized clinical trial of PC-HIV. We included adults who were on HAART at Pelotas HIV/AIDS Assistance Service between June 2006 and July 2007 and for whom information on treatment adherence, viral load and CD4+ cell count was available. Pregnant women were excluded. We obtained clinical data from medical records and socio-demographic information in an interview. Therapeutic success was defined as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥95%. We included 136 patients (60% male) in the cohort study. Mean age was 40 ± 10 years, and median treatment duration was 59 months (IQR 25-93). Family income varied from 0 to 8 times the minimum wage (IQR 1·0-2·3). Therapeutic success was achieved by 90% (122 patients), and it was associated with previously undetectable viral load (PR = 1·30; 95% CI = 1·13-1·49) and treatment adherence prior to study entry (PR = 1·34; 95% CI = 1·07-1·69), independently of sex, age and previous immune status. When undetectable viral load, CD4+ cell count ≥200 cells/mm(3) and treatment adherence above 95% are included in the definition of therapeutic success, the rate was elevated (90%) and the factors associated were previous history of adherence to HAART and previous undetectable viral load. © 2014 John Wiley & Sons Ltd.

The Role of Test Context in Latent Inhibition of Conditioned Inhibition: Part of a Search for General Principles of Associative Interference

PubMed Central

Miguez, Gonzalo; Soares, Julia S.; Miller, Ralph R.

2015-01-01

Two lick-suppression experiments with rats assessed interference with behavior indicative of conditioned inhibition by a latent inhibition treatment as a function of test context. We asked what effect the test context has, given identical latent inhibition treatment in Phase 1 and identical conditioned inhibition training in Phase 2. In Experiment 1, an AAA vs. AAB context-shift design determined that latent inhibition treatment in Phase 1 attenuated behavior indicative of conditioned inhibition training administered in Phase 2 regardless of the test context, which could reflect a failure to either acquire or express conditioned inhibition. In Experiment 2, an ABA vs. ABB design found that test performance in Contexts A and B reflected the treatments that had been administered in those contexts (i.e., conditioned inhibition was observed in Context B but not A), which could reflect either context specificity of latent inhibition or context specificity of conditioned inhibition. In either case, latent inhibition of conditioned inhibition training in at least some situations was seen to reflect an expression deficit rather than an acquisition deficit. These data, in conjunction with prior reports, suggest that latent inhibition is relatively specific to the context in which it was administered, whereas conditioned inhibition is specific to its training context only when it is the second learned relationship concerning the target cue. These experiments are part of a larger effort to delineate control by the test context of two-phase associative interference as a function of the nature of target training and the nature of interference training. PMID:25875792

The role of test context in latent inhibition of conditioned inhibition: Part of a search for general principles of associative interference.

PubMed

Miguez, Gonzalo; Soares, Julia S; Miller, Ralph R

2015-09-01

In two lick suppression experiments with rats, we assessed interference with behavior indicative of conditioned inhibition by a latent inhibition treatment as a function of test context. We asked what effect the test context has, given identical latent inhibition treatments in Phase 1 and identical conditioned inhibition trainings in Phase 2. In Experiment 1, an AAA versus AAB context-shift design determined that the latent inhibition treatment in Phase 1 attenuated behavior indicative of the conditioned inhibition training administered in Phase 2, regardless of the test context, which could reflect a failure to either acquire or express conditioned inhibition. In Experiment 2, an ABA versus ABB design showed that test performance in Contexts A and B reflected the treatments that had been administered in those contexts (i.e., conditioned inhibition was observed in Context B but not A), which could reflect either the context specificity of either latent inhibition or conditioned inhibition. In either case, latent inhibition of conditioned inhibition training in at least some situations was seen to reflect an expression deficit rather than an acquisition deficit. These data, in conjunction with prior reports, suggest that latent inhibition is relatively specific to the context in which it was administered, whereas conditioned inhibition is specific to its training context only when it is the second-learned relationship concerning the target cue. These experiments are part of a larger effort to delineate control by the test context of two-phase associative interference, as a function of the nature of target training and the nature of interference training.

Postnatal functional inactivation of the entorhinal cortex or ventral subiculum has different consequences for latent inhibition-related striatal dopaminergic responses in adult rats.

PubMed

Meyer, F; Peterschmitt, Y; Louilot, A

2009-05-01

Latent inhibition has been found to be disrupted in patients with acute schizophrenia. Striatal dopaminergic dysregulation is commonly acknowledged in schizophrenia. This disease may be consecutive to a functional disconnection between integrative regions, stemming from neurodevelopmental failures. Various anomalies suggesting early abnormal brain development have been described in the entorhinal cortex (ENT) and ventral subiculum (SUB) of patients. This study examines the consequences of a neonatal transitory blockade of the left ENT or left SUB for latent inhibition-related dopamine responses in the anterior part of the dorsal striatum using in-vivo voltammetry in freely moving adult rats. Reversible inactivation of both structures in different animals was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8. Results obtained during the retention session of a three-stage latent inhibition protocol showed that the functional neonatal disconnection of the ENT or SUB caused the behavioural latent inhibition expression in pre-exposed (PE)-TTX-conditioned adult rats to disappear. After postnatal inactivation of the SUB, PE-TTX-conditioned rats displayed a reversal of the latent inhibition-related striatal dopamine responses, whereas after neonatal blockade of the ENT, dopamine changes in PE-TTX-conditioned rats monitored in the anterior striatum were between those observed in PE-phosphate-buffered-saline-conditioned and non-PE-TTX-conditioned animals. These data suggest that neonatal functional inactivation of the SUB disrupts latent inhibition-related striatal dopamine responses in adult animals more than that of the ENT. They may help improve understanding of the pathophysiology of schizophrenia.

77 FR 42964 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... the potential for ignition sources inside fuel tanks caused by latent failures, alterations, repairs, or maintenance actions, which, in combination with flammable fuel vapors, could result in a fuel tank... for fuel tank systems to satisfy Special Federal Aviation Regulation No. 88 requirements. That AD also...

A lentiviral vector that activates latent human immunodeficiency virus-1 proviruses by the overexpression of tat and that kills the infected cells.

PubMed

Macías, David; Oya, Ricardo; Saniger, Luisa; Martín, Francisco; Luque, Francisco

2009-11-01

Despite the efficient HIV-1 replication blockage achieved with current highly active antiretroviral therapy (HAART) therapies, HIV-1 persists in the body and survives in a latent state that can last for the entire life of the patient. A long-lived reservoir of latently infected CD4(+) memory T cells represents the most important sanctuary for the virus and the greatest obstacle for viral eradication. In this work, we present an initial step toward a gene therapy approach aimed at the activation of latent provirus to induce the death of latently infected T cells. Latent HIV-1 infection is characterized by the failure of viral gene expression as a consequence of uninitiated or aborted transcription. We have constructed an HIV-1-based lentiviral vector (p5p53RTAT3) that expresses the viral trans-activating protein Tat in a drug-regulated manner and p53 in a Rev-dependent manner. We have demonstrated that the Tat-expressed protein from p5p53RTAT3 vector reactivates latent HIV-1 proviruses in J1.1 and ACH-2 cell lines and promotes p53-induced apoptosis in the presence of Rev. Our system was able to trigger the trans-activation of the provirus 5' long terminal repeat (LTR), stimulate the expression of the Rev protein from a tat-defective provirus, and provoke apoptosis selectively in the cells transfected with a tat-defective HIV-1 provirus in contrast to those with no HIV-1 provirus. However, the Rev-dependent p53 killing of latently infected cells was not effective enough for complete elimination of the awakened HIV-1 viruses. In summary, we have developed a vector system that is efficient in activating latent HIV-1 proviruses but that needs further improvement to kill infected cells.

Multivariate analysis of fears in dental phobic patients according to a reduced FSS-II scale.

PubMed

Hakeberg, M; Gustafsson, J E; Berggren, U; Carlsson, S G

1995-10-01

This study analyzed and assessed dimensions of a questionnaire developed to measure general fears and phobias. A previous factor analysis among 109 dental phobics had revealed a five-factor structure with 22 items and an explained total variance of 54%. The present study analyzed the same material using a multivariate statistical procedure (LISREL) to reveal structural latent variables. The LISREL analysis, based on the correlation matrix, yielded a chi-square of 216.6 with 195 degrees of freedom (P = 0.138) and showed a model with seven latent variables. One was a general fear factor correlated to all 22 items. The other six factors concerned "Illness & Death" (5 items), "Failures & Embarrassment" (5 items), "Social situations" (5 items), "Physical injuries" (4 items), "Animals & Natural phenomena" (4 items). One item (opposite sex) was included in both "Failures & Embarrassment" and "Social situations". The last factor, "Social interaction", combined all the items in "Failures & Embarrassment" and "Social situations" (9 items). In conclusion, this multivariate statistical analysis (LISREL) revealed and confirmed a factor structure similar to our previous study, but added two important dimensions not shown with a traditional factor analysis. This reduced FSS-II version measures general fears and phobias and may be used on a routine clinical basis as well as in dental phobia research.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

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

A. Monti Hughes; ECC Pozzi; S. Thorp

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

Current Launch Vehicle Practice and Data Base Assessment. Volume 1. Executive Summary and Report Body

DTIC Science & Technology

1989-06-01

resulted in an increase of the intermediate seal purge pressure, revised redlines, and a design change from a lift-off seal to a labyrinth seal design. This...engine 0003 caused fa&i!ure of the primary lox seal and an uncontained engine fire. The redline cut was set by a HPOTP overspeed. This failure...occurred as a result of undetected internal HEX damage caused during arc welding which resulted in an engine fire. HEX coil leakage resulted in an

Depression and Delinquency Covariation in an Accelerated Longitudinal Sample of Adolescents

ERIC Educational Resources Information Center

Kofler, Michael J.; McCart, Michael R.; Zajac, Kristyn; Ruggiero, Kenneth J.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2011-01-01

Objectives: The current study tested opposing predictions stemming from the failure and acting out theories of depression-delinquency covariation. Method: Participants included a nationwide longitudinal sample of adolescents (N = 3,604) ages 12 to 17. Competing models were tested with cohort-sequential latent growth curve modeling to determine…

75 FR 906 - Airworthiness Directives; The Boeing Company Model 747-400, -400D, and -400F Series Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

... aircraft for which a manufacturer's maintenance manual or instructions for continued airworthiness has been... maintenance program by incorporating new airworthiness limitations (AWLs) for fuel tank systems to satisfy... latent failures, alterations, repairs, or maintenance actions, which, in combination with flammable fuel...

Predicting Learned Helplessness Based on Personality

ERIC Educational Resources Information Center

Maadikhah, Elham; Erfani, Nasrollah

2014-01-01

Learned helplessness as a negative motivational state can latently underlie repeated failures and create negative feelings toward the education as well as depression in students and other members of a society. The purpose of this paper is to predict learned helplessness based on students' personality traits. The research is a predictive…

2005 DoD Diminishing Manufacturing Sources and Material Shortages

DTIC Science & Technology

2005-12-15

free Solder Issues Temperature stress Prevailing Pb-free solder replacement ( SnAgCu ) has ~35°C higher reflow temperature Infant mortality Latent...SnCu, SnAgCu Few microns to over 1mm Electrically conductive Crystalline Whisker induced failures: Short Circuit – bridges two adjacent pins Metal

The role of biaxial stresses in discriminating between meaningful and illusory composite failure theories

NASA Technical Reports Server (NTRS)

Hart-Smith, L. J.

1992-01-01

The irrelevance of most composite failure criteria to conventional fiber-polymer composites is claimed to have remained undetected primarily because the experiments that can either validate or disprove them are difficult to perform. Uniaxial tests are considered inherently incapable of validating or refuting any composite failure theory because so much of the total load is carried by the fibers aligned in the direction of the load. The Ten-Percent Rule, a simple rule-of-mixtures analysis method, is said to work well only because of this phenomenon. It is stated that failure criteria can be verified for fibrous composites only by biaxial tests, with orthogonal in-plane stresses of the same as well as different signs, because these particular states of combined stress reveal substantial differences between the predictions of laminate strength made by various theories. Three scientifically plausible failure models for fibrous composites are compared, and it is shown that only the in-plane shear test (orthogonal tension and compression) is capable of distinguishing between them. This is because most theories are 'calibrated' against the measured uniaxial tension and compression tests and any cross-plied laminate tests dominated by those same states of stress must inevitably 'confirm' the theory.

Performance Characteristics of the Reverse Syphilis Screening Algorithm in a Population With a Moderately High Prevalence of Syphilis.

PubMed

Rourk, Angela R; Nolte, Frederick S; Litwin, Christine M

2016-11-01

With the recent introduction of automated treponemal tests, a new reverse syphilis algorithm has been proposed and now used by many clinical laboratories. We analyzed the impact of instituting the reverse screening syphilis algorithm in a laboratory that serves a geographic area with a moderately high prevalence of syphilis infection. Serum samples sent for syphilis testing were tested using a treponemal enzyme immunoassay (EIA) as the screening assay. EIA reactive samples were tested by rapid plasma reagin (RPR) and titered to end point if reactive. RPR nonreactive samples were analyzed by the Treponema pallidum particle agglutination test (TP-PA). Pertinent medical records were reviewed for false-reactive screens and samples with evidence of past syphilis infection. Among 10,060 patients tested, 502 (5%) were reactive on the initial EIA screen. The RPR was reactive in 150 (1.5%). TP-PA testing determined that 103 (1.0%) were falsely reactive on initial EIA screen. The reverse screening algorithm, however, identified 242 (2.4%) with evidence of latent, secondary, or past syphilis, 21 of whom had no or unknown prior treatment with antibiotics. Despite a 1.0% false-reactive rate, the reverse syphilis algorithm detected 21 patients with possible latent syphilis that may have gone undetected by traditional syphilis screening. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions

PubMed Central

Polizzotto, Mark N.; Chen, Grace; Tressler, Randall L.; Godfrey, Catherine

2015-01-01

Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been “cured” of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment. PMID:26224205

Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions.

PubMed

Polizzotto, Mark N; Chen, Grace; Tressler, Randall L; Godfrey, Catherine

2015-09-01

Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been "cured" of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment.

Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

PubMed Central

Hurst, Jacob; Hoffmann, Matthias; Pace, Matthew; Williams, James P.; Thornhill, John; Hamlyn, Elizabeth; Meyerowitz, Jodi; Willberg, Chris; Koelsch, Kersten K.; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David A.; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Babiker, Abdel; Weber, Jonathan; Kelleher, Anthony D.; Phillips, Rodney E.; Frater, John

2015-01-01

Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication. PMID:26449164

Product advertising versus ideas advertising.

PubMed

Harvey, P

1998-01-01

Social marketing programs which promote the use of a product, such as a condom, have certain advantages over programs which simply try to convince people to change their behavior. Of considerable importance, the success or failure of a social marketing program can be readily assessed through the level of sales of the promoted product. Most programs designed to alleviate poverty or advance social goals are extremely hard to measure, often leading to program inefficiency and even undetected failure. However, when a socially motivated program depends upon product sales, those sales can be quickly measured. Even though sales statistics alone are not enough to accurately judge the impact of family planning programs, they can still say much about relative program efficiencies. The brand advantage of promoting and selling branded products is also explained.

Development of the Nontechnical Skills for Officers of the Deck (NTSOD) Rating Form

DTIC Science & Technology

2010-12-01

organizational model of human error commonly described as the ‘ Swiss Cheese ’ model. This model allows for the identification of active failures and latent...complete list). The authors did identify organizational and management issues as underlying causes to mishaps, similar to Reason’s Swiss Cheese model. 24

Radiation-induced antrochoanal fibrosarcoma.

PubMed

Liddington, M I; Harrison, R F; Booth, A P; Das Gupta, A R

1992-06-01

Therapeutic radiation for malignant conditions is known to cause sarcomatous change in an irradiated field after a latent period; equally this change may occur following radiotherapy to benign conditions which may result in a more difficult management problem later. Radiotherapy to benign conditions should be reserved for use after failure of conventional surgery or other interventional techniques.

75 FR 68245 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... shutoff system wiring. This proposed AD was prompted by a possible latent failure in the fire handle... engine fuel fire shutoff handle is activated. Separating the fire handle shutoff system wiring will... handle shutoff system wiring. FAA's Determination We are proposing this AD because we evaluated all the...

The Semantic Distance Task: Quantifying Semantic Distance with Semantic Network Path Length

ERIC Educational Resources Information Center

Kenett, Yoed N.; Levi, Effi; Anaki, David; Faust, Miriam

2017-01-01

Semantic distance is a determining factor in cognitive processes, such as semantic priming, operating upon semantic memory. The main computational approach to compute semantic distance is through latent semantic analysis (LSA). However, objections have been raised against this approach, mainly in its failure at predicting semantic priming. We…

Cognitive Performance in Older Adults with Stable Heart Failure: Longitudinal Evidence for Stability and Improvement

PubMed Central

Alosco, Michael L.; Garcia, Sarah; Spitznagel, Mary Beth; van Dulmen, Manfred; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

2013-01-01

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. PMID:23906182

Gardening can induce pulmonary failure: Aspergillus ARDS in an immunocompetent patient, a case report.

PubMed

Jung, Nina; Mronga, Silke; Schroth, Susanne; Vassiliou, Timon; Sommer, Frank; Walthers, Eduard; Aepinus, Christian; Jerrentrup, Andreas; Vogelmeier, Claus; Holland, Angelique; Koczulla, Rembert

2014-11-26

Acute Aspergillus fumigatus infection in immunocompetent patients is rare. This is the first known case of a patient who survived Aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ECMO) and antifungal therapy. An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure. Owing to her severe clinical condition, she was treated for acute respiratory distress syndrome (ARDS) with veno-venous ECMO. Empiric antifungal therapy comprising voriconazole was also initiated owing to her history and a previous case report of aspergillosis after plant mulch exposure, though there was no microbiological proof at the time. A. fumigatus was later cultured and detected on antibody testing. The patient recovered, and ECMO was discontinued 1 week later. After 7 days of antifungal treatment, Aspergillus antibodies were undetectable. In cases of sepsis that occur after gardening, clinicians should consider Aspergillus inhalation as an aetiology, and early antimycotic therapy is recommended.

All That Glisters Is Not Gold: Sampling-Process Uncertainty in Disease-Vector Surveys with False-Negative and False-Positive Detections

PubMed Central

Abad-Franch, Fernando; Valença-Barbosa, Carolina; Sarquis, Otília; Lima, Marli M.

2014-01-01

Background Vector-borne diseases are major public health concerns worldwide. For many of them, vector control is still key to primary prevention, with control actions planned and evaluated using vector occurrence records. Yet vectors can be difficult to detect, and vector occurrence indices will be biased whenever spurious detection/non-detection records arise during surveys. Here, we investigate the process of Chagas disease vector detection, assessing the performance of the surveillance method used in most control programs – active triatomine-bug searches by trained health agents. Methodology/Principal Findings Control agents conducted triplicate vector searches in 414 man-made ecotopes of two rural localities. Ecotope-specific ‘detection histories’ (vectors or their traces detected or not in each individual search) were analyzed using ordinary methods that disregard detection failures and multiple detection-state site-occupancy models that accommodate false-negative and false-positive detections. Mean (±SE) vector-search sensitivity was ∼0.283±0.057. Vector-detection odds increased as bug colonies grew denser, and were lower in houses than in most peridomestic structures, particularly woodpiles. False-positive detections (non-vector fecal streaks misidentified as signs of vector presence) occurred with probability ∼0.011±0.008. The model-averaged estimate of infestation (44.5±6.4%) was ∼2.4–3.9 times higher than naïve indices computed assuming perfect detection after single vector searches (11.4–18.8%); about 106–137 infestation foci went undetected during such standard searches. Conclusions/Significance We illustrate a relatively straightforward approach to addressing vector detection uncertainty under realistic field survey conditions. Standard vector searches had low sensitivity except in certain singular circumstances. Our findings suggest that many infestation foci may go undetected during routine surveys, especially when vector density is low. Undetected foci can cause control failures and induce bias in entomological indices; this may confound disease risk assessment and mislead program managers into flawed decision making. By helping correct bias in naïve indices, the approach we illustrate has potential to critically strengthen vector-borne disease control-surveillance systems. PMID:25233352

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

PubMed

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

2017-04-15

Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. Copyright © 2017 Tsai et al.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

PubMed Central

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

2017-01-01

ABSTRACT Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. PMID:28179531

Mask induction despite circuit obstruction: an unrecognized hazard of relying on automated machine check technology.

PubMed

Yang, Kamie K; Lewis, Ian H

2014-06-15

Various equipment malfunctions of anesthesia gas delivery systems have been previously reported. Our profession increasingly uses technology as a means to prevent these errors. We report a case of a near-total anesthesia circuit obstruction that went undetected before the induction of anesthesia despite the use of automated machine check technology. This case highlights that automated machine check modules can fail to detect severe equipment failure and demonstrates how, even in this era of expanding technology, manual checks still remain essential components of safe care.

[Transesophageal echocardiography diagnosis of ruptured aneurysm of the Valsalva sinus associated with aneurysm of the interatrial septum].

PubMed

Imperadore, Ferdinando; Ferro, Aldo; Graffigna, Angelo; Vergara, Giuseppe

2002-01-01

Aneurysms of the sinus of Valsalva are uncommon heart defects that often remain undetected unless rupture occurs. They have been reported in association with other cardiac anomalies. The present case report deals with a 51-year-old man who was referred to our division with a diagnosis of recent-onset progressive heart failure. Echocardiographic evaluation, both transthoracic and transesophageal, disclosed rupture of an aneurysm of the non-coronary sinus of Valsalva into the right atrium. This anomaly was associated with an aneurysm of the atrial septum.

Methods to Find the Number of Latent Skills

ERIC Educational Resources Information Center

Beheshti, Behzad; Desmarais, Michel C.; Naceur, Rhouma

2012-01-01

Identifying the skills that determine the success or failure to exercises and question items is a difficult task. Multiple skills may be involved at various degree of importance, and skills may overlap and correlate. In an effort towards the goal of finding the skills behind a set of items, we investigate two techniques to determine the number of…

Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

ERIC Educational Resources Information Center

Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

2008-01-01

Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

A Note on Sample Size and Solution Propriety for Confirmatory Factor Analytic Models

ERIC Educational Resources Information Center

Jackson, Dennis L.; Voth, Jennifer; Frey, Marc P.

2013-01-01

Determining an appropriate sample size for use in latent variable modeling techniques has presented ongoing challenges to researchers. In particular, small sample sizes are known to present concerns over sampling error for the variances and covariances on which model estimation is based, as well as for fit indexes and convergence failures. The…

Reflections on the surface energy imbalance problem

Treesearch

Ray Leuning; Eva van Gorsela; William J. Massman; Peter R. Isaac

2012-01-01

The 'energy imbalance problem' in micrometeorology arises because at most flux measurement sites the sum of eddy fluxes of sensible and latent heat (H + λE) is less than the available energy (A). Either eddy fluxes are underestimated or A is overestimated. Reasons for the imbalance are: (1) a failure to satisfy the fundamental assumption of one-...

Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency

NASA Technical Reports Server (NTRS)

Kim, Chun-Hyung; Zabetian, Cyrus P.; Cubells, Joseph F.; Cho, Sonhae; Biaggioni, Italo; Cohen, Bruce M.; Robertson, David; Kim, Kwang-Soo

2002-01-01

Norepinephrine (NE), a key neurotransmitter of the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) that catalyzes oxidation of dopamine (DA) to NE. NE deficiency is a congenital disorder of unknown etiology, in which affected patients suffer profound autonomic failure. Biochemical features of the syndrome include undetectable tissue and circulating levels of NE and epinephrine, elevated levels of DA, and undetectable levels of DBH. Here, we report identification of seven novel variants including four potentially pathogenic mutations in the human DBH gene (OMIM 223360) from analysis of two unrelated patients and their families. Both patients are compound heterozygotes for variants affecting expression of DBH protein. Each carries one copy of a T-->C transversion in the splice donor site of DBH intron 1, creating a premature stop codon. In patient 1, there is a missense mutation in DBH exon 2. Patient 2 carries missense mutations in exons 1 and 6 residing in cis. We propose that NE deficiency is an autosomal recessive disorder resulting from heterogeneous molecular lesions at DBH. Copyright 2002 Wiley-Liss, Inc.

Autoimmune hyperthyroidism due to secondary adrenal insufficiency: resolution with glucocorticoids.

PubMed

Skamagas, Maria; Geer, Eliza B

2011-01-01

To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.

AIDS Diarrhea and Antiretroviral Drug Concentrations: A Matched-Pair Cohort Study in Port au Prince, Haiti

PubMed Central

Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne; Miller, Erica; Kashuba, Angela; Jennings, Steven; Dupnik, Kathryn; Samie, Amidou; Eyma, Etna; Guerrant, Richard; Pape, Jean; Fitzgerald, Daniel

2011-01-01

Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea. PMID:21633022

Understanding adverse events: human factors.

PubMed Central

Reason, J

1995-01-01

(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole. PMID:10151618

Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization.

PubMed

Li, Le-Jun; Zhang, Feng-Bin; Liu, Shu-Yuan; Tian, Yong-Hong; Le, Fang; Wang, Li-Ya; Lou, Hang-Ying; Xu, Xiang-Rong; Huang, He-Feng; Jin, Fan

2014-06-01

In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients without gACE on sperm (23 of 25) manifested a TT genotype of the rs4316 single-nucleotide polymorphism of ACE. Overall, our results indicate that the absence of gACE expression is responsible for TFF and LFRs by IVF. The rs4316 polymorphism of ACE might be associated with infertility in those patients. We conclude that sperm lacking gACE may be recognized before commencing IVF and that the patients may be directed instead to consider intracytoplasmic sperm injection. © 2014 by the Society for the Study of Reproduction, Inc.

AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of relapsed microscopic polyangiitis after initiation of dialysis.

PubMed

Sugahara, Mai; Nishi, Takahiro; Tanaka, Shinji; Kurita, Noriaki; Sai, Keiko; Kano, Tatsuya; Nishio, Kyosuke; Sugimoto, Tokuichiro; Mise, Naobumi

2013-11-01

We report two patients with rheumatoid arthritis (RA) who were suspected of microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old woman with RA diagnosed at the age of 38 years and treated successfully with gold compounds. At the age of 43 years, she presented with progressive renal dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was not measured on that occasion. She reached end-stage renal failure within 4 months and started peritoneal dialysis. Eight years later, soon after she was switched to hemodialysis, she developed fever of unknown origin. MPO-ANCA was elevated to 37 EU, although there were no other signs or symptoms suggestive of vasculitis. After taking prednisolone orally (10 mg/day), her fever withdrew, and MPO-ANCA became undetectable. Case 2 was a 71-year-old woman with RA diagnosed at the age of 60 years and treated with gold compounds. She developed renal failure of unknown cause (no biopsy was performed), and started hemodialysis at the age of 69 years. One year later, she presented with fever and subsequently developed cough with hemoptysis. MPO-ANCA was elevated to 62 EU. Treatment with azathioprine 50 mg and prednisolone 35 mg daily brought remarkable clinical improvement, and MPO-ANCA became undetectable. These cases highlight the importance of measuring ANCA even in RA patients on dialysis who present with fever of unknown origin or with underlying kidney disease of uncertain etiology.

Parent-Child Endorsement Discrepancies among Youth at Chronic-Risk for Depression.

PubMed

Makol, Bridget A; Polo, Antonio J

2017-11-10

Depression is one of the most common mental health problems among U.S. adolescents, particularly among Latinos. Parent-child ratings of the presence and severity of child depressive symptoms show only low-to-moderate agreement. However, research has failed to examine discrepancies in populations with the highest levels of unmet need and little is known about patterns and predictors of parent-child agreement in ratings of depressive symptoms among ethnic minority families in community settings. Using a sample of 184 low-income, predominantly Latino, 5th through 7th grade students (63.6% female) at chronic risk for depression, this study utilized exploratory Latent Class Analysis (LCA) to uncover patterns of parent-child endorsement of core diagnostic depressive symptoms. Overall, children reported higher levels of core (i.e., depressed mood, anhedonia, irritability) and secondary (e.g., sleep disturbances) depressive symptoms relative to their parents. The three latent classes identified include a low endorsement and high agreement class (LH), high endorsement and high agreement class (HH), and high child endorsement and low agreement class (HCL). Multinomial regression models revealed that previous mental health service use and higher externalizing problems were associated with HH class membership, relative to HCL class membership. Findings provide evidence that a substantial number of children may have depressive symptoms that go undetected by their parents. Access to services among children at-risk for depression may be increased with psychoeducation to improve parental awareness and stigma reduction.

Managing Errors to Reduce Accidents in High Consequence Networked Information Systems

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

Ganter, J.H.

1999-02-01

Computers have always helped to amplify and propagate errors made by people. The emergence of Networked Information Systems (NISs), which allow people and systems to quickly interact worldwide, has made understanding and minimizing human error more critical. This paper applies concepts from system safety to analyze how hazards (from hackers to power disruptions) penetrate NIS defenses (e.g., firewalls and operating systems) to cause accidents. Such events usually result from both active, easily identified failures and more subtle latent conditions that have resided in the system for long periods. Both active failures and latent conditions result from human errors. We classifymore » these into several types (slips, lapses, mistakes, etc.) and provide NIS examples of how they occur. Next we examine error minimization throughout the NIS lifecycle, from design through operation to reengineering. At each stage, steps can be taken to minimize the occurrence and effects of human errors. These include defensive design philosophies, architectural patterns to guide developers, and collaborative design that incorporates operational experiences and surprises into design efforts. We conclude by looking at three aspects of NISs that will cause continuing challenges in error and accident management: immaturity of the industry, limited risk perception, and resource tradeoffs.« less

A cascading failure model for analyzing railway accident causation

NASA Astrophysics Data System (ADS)

Liu, Jin-Tao; Li, Ke-Ping

2018-01-01

In this paper, a new cascading failure model is proposed for quantitatively analyzing the railway accident causation. In the model, the loads of nodes are redistributed according to the strength of the causal relationships between the nodes. By analyzing the actual situation of the existing prevention measures, a critical threshold of the load parameter in the model is obtained. To verify the effectiveness of the proposed cascading model, simulation experiments of a train collision accident are performed. The results show that the cascading failure model can describe the cascading process of the railway accident more accurately than the previous models, and can quantitatively analyze the sensitivities and the influence of the causes. In conclusion, this model can assist us to reveal the latent rules of accident causation to reduce the occurrence of railway accidents.

Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.

PubMed

Liang, Emily C; Sceats, Lindsay; Bayless, Nicholas L; Strauss-Albee, Dara M; Kubo, Jessica; Grant, Philip M; Furman, David; Desai, Manisha; Katzenstein, David A; Davis, Mark M; Zolopa, Andrew R; Blish, Catherine A

2014-08-01

Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation. Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Establishment of design criteria for acceptable failure modes and fail safe considerations for the space shuttle structural system

NASA Technical Reports Server (NTRS)

Westrup, R. W.

1972-01-01

Investigations of fatigue life, and safe-life and fail-safe design concepts as applied to space shuttle structure are summarized. The results are evaluated to select recommended structural design criteria to provide assurance that premature failure due to propagation of undetected crack-like defects will not occur during shuttle operational service. The space shuttle booster, GDC configuration B-9U, is selected as the reference vehicle. Structural elements used as basis of detail analyses include wing spar caps, vertical stabilizer skins, crew compartment skin, orbiter support frame, and propellant tank shell structure. Fatigue life analyses of structural elements are performed to define potential problem areas and establish upper limits of operating stresses. Flaw growth analyses are summarized in parametric form over a range of initial flaw types and sizes, operating stresses and service life requirements. Service life of 100 to 500 missions is considered.

Simplified failure sequence evaluation of reactor pressure vessel head corroding in-core instrumentation assembly

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

McVicker, J.P.; Conner, J.T.; Hasrouni, P.N.

1995-11-01

In-Core Instrumentation (ICI) assemblies located on a Reactor Pressure Vessel Head have a history of boric acid leakage. The acid tends to corrode the nuts and studs which fasten the flanges of the assembly, thereby compromising the assembly`s structural integrity. This paper provides a simplified practical approach in determining the likelihood of an undetected progressing assembly stud deterioration, which would lead to a catastrophic loss of reactor coolant. The structural behavior of the In-Core Instrumentation flanged assembly is modeled using an elastic composite section assumption, with the studs transmitting tension and the pressure sealing gasket experiencing compression. Using the abovemore » technique, one can calculate the flange relative deflection and the consequential coolant loss flow rate, as well as the stress in any stud. A solved real life example develops the expected failure sequence and discusses the exigency of leak detection for safe shutdown. In the particular case of Calvert Cliffs Nuclear Power Plant (CCNPP) it is concluded that leak detection occurs before catastrophic failure of the ICI flange assembly.« less

Measurement and analysis of workload effects on fault latency in real-time systems

NASA Technical Reports Server (NTRS)

Woodbury, Michael H.; Shin, Kang G.

1990-01-01

The authors demonstrate the need to address fault latency in highly reliable real-time control computer systems. It is noted that the effectiveness of all known recovery mechanisms is greatly reduced in the presence of multiple latent faults. The presence of multiple latent faults increases the possibility of multiple errors, which could result in coverage failure. The authors present experimental evidence indicating that the duration of fault latency is dependent on workload. A synthetic workload generator is used to vary the workload, and a hardware fault injector is applied to inject transient faults of varying durations. This method makes it possible to derive the distribution of fault latency duration. Experimental results obtained from the fault-tolerant multiprocessor at the NASA Airlab are presented and discussed.

Finding Success in Failure: Using Latent Profile Analysis to Examine Heterogeneity in Psychosocial Functioning among Heavy Drinkers Following Treatment

PubMed Central

Wilson, Adam D.; Bravo, Adrian J.; Witkiewitz, Katie

2016-01-01

Aims To estimate differences in post-treatment psychosocial functioning among treatment “failures” (i.e., heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials, and to compare these levels of functioning to those of the purported treatment “successes” (i.e., non-heavy drinkers). Design Separate latent profile analyses of data from COMBINE and Project MATCH, comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. Setting Eleven U.S. academic sites in COMBINE, 27 U.S. treatment sites local to nine research sites in Project MATCH. Participants 962 individuals in COMBINE (69% male, 77% white, mean age: 44 years) treated January 2001 to January 2004 and 1,528 individuals in Project MATCH (75% male, 80% white, mean age: 40 years) treated April 1991 to September 1994. Measurements In COMBINE, we analyzed health, quality of life, mental health symptoms, and alcohol consequences 12-months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms, and alcohol consequences 15-months post-baseline. Findings Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment “failures,” characterized by high-functioning, average-functioning, and low-functioning individuals. The high-functioning treatment “failures” were generally performing better across measures of psychosocial functioning at follow-up than participants designated treatment “successes” by virtue of being abstainers or light drinkers. Conclusions Current Food and Drug Administration guidance to use heavy drinking as indicative of treatment “failure” fails to take into account substantial psychosocial improvements made by individuals who continue to occasionally drink heavily post-treatment. PMID:27367263

Holographic Reciprocity Law Failure, with Applications to the Three-Dimensional Display of Medical Data

NASA Astrophysics Data System (ADS)

Johnson, Kristina Mary

In 1973 the computerized tomography (CT) scanner revolutionized medical imaging. This machine can isolate and display in two-dimensional cross-sections, internal lesions and organs previously impossible to visualize. The possibility of three-dimensional imaging however is not yet exploited by present tomographic systems. Using multiple-exposure holography, three-dimensional displays can be synthesizing from two-dimensional CT cross -sections. A multiple-exposure hologram is an incoherent superposition of many individual holograms. Intuitively it is expected that holograms recorded with equal energy will reconstruct images with equal brightness. It is found however, that holograms recorded first are brighter than holograms recorded later in the superposition. This phenomena is called Holographic Reciprocity Law Failure (HRLF). Computer simulations of latent image formation in multiple-exposure holography are one of the methods used to investigate HRLF. These simulations indicate that it is the time between individual exposures in the multiple -exposure hologram that is responsible for HRLF. This physical parameter introduces an asymmetry into the latent image formation process that favors the signal of previously recorded holograms over holograms recorded later in the superposition. The origin of this asymmetry lies in the dynamics of latent image formation, and in particular in the decay of single-atom latent image specks, which have lifetimes that are short compared to typical times between exposures. An analytical model is developed for a double exposure hologram that predicts a decrease in the brightness of the second exposure as compared to the first exposure as the time between exposures increases. These results are consistent with the computer simulations. Experiments investigating the influence of this parameter on the diffraction efficiency of reconstructed images in a double exposure hologram are also found to be consistent with the computer simulations and analytical results. From this information, two techniques are presented that correct for HRLF, and succeed in reconstructing multiple holographic images of CT cross-sections with equal brightness. The multiple multiple-exposure hologram is a new hologram that increases the number of equally bright images that can be superimposed on one photographic plate.

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

PubMed

Berenguer, Juan; Polo, Rosa; Lozano, Fernando; López Aldeguer, José; Antela, Antonio; Arribas, José Ramón; Asensi, Víctor; Blanco, José Ramón; Clotet, Bonaventura; Domingo, Pere; Galindo, María José; Gatell, José María; González-García, Juan; Iribarren, José Antonio; Locutura, Jaime; López, Juan Carlos; Mallolas, Josep; Martínez, Esteban; Miralles, Celia; Miró, José M; Moreno, Santiago; Palacios, Rosario; Pérez Elías, María Jesús; Pineda, Juan Antonio; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz, Jesús; Tuset, Montserrat; Vidal, Francesc; Rivero, Antonio

2014-01-01

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Executive summary of the GESIDA/National AIDS Plan Consensus Document on Antiretroviral Therapy in Adults Infected by the Human Immunodeficiency Virus (Updated January 2017).

PubMed

2017-05-31

Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer). Copyright © 2017. Publicado por Elsevier España, S.L.U.

Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure.

PubMed

Gada Saxena, S; Desai, K; Shewale, L; Ranjan, P; Saranath, D

2012-08-01

Constitutional chromosomal aberrations contribute to infertility and repeated miscarriage leading to reproductive failure in couples. These aberrations may show no obvious clinical manifestations and remain undetected across multiple generations. However, infertility or recurrent spontaneous pregnancy loss, and/or genotypic/phenotypic aberrations may be manifested in the progeny during gametogenesis. The current study was a retrospective analysis to examine the chromosomal aberrations and prevalence in 2000 couples of Indian ethnicity with reproductive failure. Cytogenetic analysis via conventional G-band karyotyping analysis was carried out on phytohaemagglutinin stimulated peripheral blood lymphocytes, cultured in RPMI1640 medium. The chromosomes were enumerated as per International System for Human Cytogenetic Nomenclature at 500-550 band resolution, and recorded in the screening sheets. Chromosomal aberrations were detected in a total of 110 (2.78%) couples, with structural chromosomal aberrations in 88 cases including reciprocal translocations in 56 cases, Robertsonian translocations in 16 cases, inversions in eight cases, deletions in three cases, derivative chromosomes in five cases and numerical chromosome aberrations in 23 cases. The study emphasizes the importance of cytogenetic work up in both the partners associated with a history of reproductive failure. Genetic counselling with an option of prenatal diagnosis should be offered to couples with chromosomal aberrations. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Semi-parametric Multivariate Gap-filling Model for Eddy Covariance Latent Heat Flux

NASA Astrophysics Data System (ADS)

Li, M.; Chen, Y.

2010-12-01

Quantitative descriptions of latent heat fluxes are important to study the water and energy exchanges between terrestrial ecosystems and the atmosphere. The eddy covariance approaches have been recognized as the most reliable technique for measuring surface fluxes over time scales ranging from hours to years. However, unfavorable micrometeorological conditions, instrument failures, and applicable measurement limitations may cause inevitable flux gaps in time series data. Development and application of suitable gap-filling techniques are crucial to estimate long term fluxes. In this study, a semi-parametric multivariate gap-filling model was developed to fill latent heat flux gaps for eddy covariance measurements. Our approach combines the advantages of a multivariate statistical analysis (principal component analysis, PCA) and a nonlinear interpolation technique (K-nearest-neighbors, KNN). The PCA method was first used to resolve the multicollinearity relationships among various hydrometeorological factors, such as radiation, soil moisture deficit, LAI, and wind speed. The KNN method was then applied as a nonlinear interpolation tool to estimate the flux gaps as the weighted sum latent heat fluxes with the K-nearest distances in the PCs’ domain. Two years, 2008 and 2009, of eddy covariance and hydrometeorological data from a subtropical mixed evergreen forest (the Lien-Hua-Chih Site) were collected to calibrate and validate the proposed approach with artificial gaps after standard QC/QA procedures. The optimal K values and weighting factors were determined by the maximum likelihood test. The results of gap-filled latent heat fluxes conclude that developed model successful preserving energy balances of daily, monthly, and yearly time scales. Annual amounts of evapotranspiration from this study forest were 747 mm and 708 mm for 2008 and 2009, respectively. Nocturnal evapotranspiration was estimated with filled gaps and results are comparable with other studies. Seasonal and daily variability of latent heat fluxes were also discussed.

Immune response to second vaccination series of hepatitis B virus among booster dose non-responders.

PubMed

Salama, Iman I; Sami, Samia M; Salama, Somaia I; Rabah, Thanaa Mahmoud; El Etreby, Lobna Ahmed; Abdel Hamid, Amany T; Elmosalami, Dalia; El Hariri, Hazem; Said, Zeinab N

2016-04-07

To evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination. After given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10 IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2(nd) vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10 IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2(nd) vaccination series. Protective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100 IU/L) and higher GMT (299.1 ± 3.6 IU/L) compared to those with undetectable 60% and 106.2 ± 12.9 IU/L respectively (P<0.05). No significant difference was detected as regards gender or residence, P>0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2(nd) vaccination series. A booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autologous neutralizing antibody to human immunodeficiency virus-1 and replication-competent virus recovered from CD4+ T-cell reservoirs in pediatric HIV-1-infected patients on HAART.

PubMed

Ching, Natascha; Nielsen-Saines, Karin A; Deville, Jaime G; Wei, Lian S; Garratty, Eileen; Bryson, Yvonne J

2010-05-01

A patient's ability to produce autologous neutralizing antibody (ANAB) to current and past HIV isolates correlates with reduced disease progression and protects against maternal-fetal transmission. Little is known about the effects of prolonged viral suppression on the ANAB response in pediatric HIV-infected patients receiving HAART because the virus is hard to isolate, except by special methods. We therefore assessed ANAB to pre-HAART PBMC virus isolates and post-HAART replication-competent virus (RCV) isolates recovered from latent CD4(+) T-cell reservoirs in perinatally HIV-infected children by using a PBMC-based assay and 90% neutralization titers. We studied two infants and three children before and after HAART. At the time of RCV isolation (n = 4), plasma HIV RNA was <50 copies/ml. At baseline, four of five children had detectable ANAB titers to concurrent pre-HAART virus isolates. Although ANAB was detected in all subjects at several time points despite prolonged HAART and undetectable viremia, the response was variable. ANAB titers to concurrent post-HAART RCV and earlier pre-HAART plasma were present in 3 children suggesting prior exposure to this virus. Post-HAART RCV isolates had reduced replication kinetics in vitro compared to pre-HAART viruses. The presence of ANAB over time suggests that low levels of viral replication may still be ongoing despite HAART. The observation of baseline ANAB activity with earlier plasma against a later RCV suggests that the "latent" reservoir may be established early in life before HAART.

Assessing Psychopathy Among Justice Involved Adolescents with the PCL: YV: An Item Response Theory Examination Across Gender

PubMed Central

Tsang, Siny; Schmidt, Karen M.; Vincent, Gina M.; Salekin, Randall T.; Moretti, Marlene M.; Odgers, Candice L.

2014-01-01

This study used an item response theory (IRT) model and a large adolescent sample of justice involved youth (N = 1,007, 38% female) to examine the item functioning of the Psychopathy Checklist – Youth Version (PCL: YV). Items that were most discriminating (or most sensitive to changes) of the latent trait (thought to be psychopathy) among adolescents included “Glibness/superficial charm”, “Lack of remorse”, and “Need for stimulation”, whereas items that were least discriminating included “Pathological lying”, “Failure to accept responsibility”, and “Lacks goals.” The items “Impulsivity” and “Irresponsibility” were the most likely to be rated high among adolescents, whereas “Parasitic lifestyle”, and “Glibness/superficial charm” were the most likely to be rated low. Evidence of differential item functioning (DIF) on four of the 13 items was found between boys and girls. “Failure to accept responsibility” and “Impulsivity” were endorsed more frequently to describe adolescent girls than boys at similar levels of the latent trait, and vice versa for “Grandiose sense of self-worth” and “Lacks goals.” The DIF findings suggest that four PCL: YV items function differently between boys and girls. PMID:25580672

Fear of failure, psychological stress, and burnout among adolescent athletes competing in high level sport.

PubMed

Gustafsson, H; Sagar, S S; Stenling, A

2017-12-01

The purpose of this study was to investigate fear of failure in highly competitive junior athletes and the association with psychological stress and burnout. In total 258 athletes (152 males and 108 females) ranged in age from 15 to 19 years (M = 17.4 years, SD = 1.08) participated. Athletes competed in variety of sports including both team and individual sports. Results showed in a variable-oriented approach using regression analyses that one dimension, fear of experiencing shame and embarrassment had a statistically significant effect on perceived psychological stress and one dimension of burnout, reduced sense of accomplishment. However, adopting a person-oriented approach using latent class analysis, we found that athletes with high levels of fear failure on all dimensions scored high on burnout. We also found another class with high scores on burnout. These athletes had high scores on the individual-oriented dimensions of fear of failure and low scores on the other oriented fear of failure dimensions. The findings indicate that fear of failure is related to burnout and psychological stress in athletes and that this association is mainly associated with the individual-oriented dimensions of fear of failure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis

PubMed Central

Abraham, Albin; Karakurum, Ali

2013-01-01

Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature. PMID:23964037

Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis.

PubMed

Abraham, Albin; Karakurum, Ali

2013-08-20

Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature.

Three Cs in measurement models: causal indicators, composite indicators, and covariates.

PubMed

Bollen, Kenneth A; Bauldry, Shawn

2011-09-01

In the last 2 decades attention to causal (and formative) indicators has grown. Accompanying this growth has been the belief that one can classify indicators into 2 categories: effect (reflective) indicators and causal (formative) indicators. We argue that the dichotomous view is too simple. Instead, there are effect indicators and 3 types of variables on which a latent variable depends: causal indicators, composite (formative) indicators, and covariates (the "Three Cs"). Causal indicators have conceptual unity, and their effects on latent variables are structural. Covariates are not concept measures, but are variables to control to avoid bias in estimating the relations between measures and latent variables. Composite (formative) indicators form exact linear combinations of variables that need not share a concept. Their coefficients are weights rather than structural effects, and composites are a matter of convenience. The failure to distinguish the Three Cs has led to confusion and questions, such as, Are causal and formative indicators different names for the same indicator type? Should an equation with causal or formative indicators have an error term? Are the coefficients of causal indicators less stable than effect indicators? Distinguishing between causal and composite indicators and covariates goes a long way toward eliminating this confusion. We emphasize the key role that subject matter expertise plays in making these distinctions. We provide new guidelines for working with these variable types, including identification of models, scaling latent variables, parameter estimation, and validity assessment. A running empirical example on self-perceived health illustrates our major points.

CHBPR: ANGIOTENSIN II, INDEPENDENT OF PLASMA RENIN ACTIVITY, CONTRIBUTES TO THE HYPERTENSION OF AUTONOMIC FAILURE

PubMed Central

Arnold, Amy C.; Okamoto, Luis E.; Gamboa, Alfredo; Shibao, Cyndya; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2013-01-01

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. While the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable suggesting renin-angiotensin pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that angiotensin II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating angiotensin II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/ml, n=11) compared to matched healthy controls (27±4 pg/ml, n=10; p=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/ml/hr, respectively; p=0.449). To determine the contribution of angiotensin II to supine hypertension in these patients, we administered the AT1 receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mmHg at 6 hours after administration (p<0.05), decreased nocturnal urinary sodium excretion (p=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of the captopril on supine blood pressure in a subset of these patients. These findings suggest that angiotensin II formation in autonomic failure is independent of plasma renin activity, and perhaps angiotensin converting enzyme. Furthermore, these studies suggest that elevations in angiotensin II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT1 receptor blockers for treatment of these patients. PMID:23266540

[A case of anterior tibial arteriovenous fistula after closed fracture of the leg].

PubMed

Touzard, R C

1975-01-01

This case permits one to emphasize the great rareness of arteriovenous fistula after closed fractures of the shaft of the tibia. Fistulas in this anterior tibial position are remarkably latent, cause no symptoms below the fistula nor symptoms of heart failure. Treatment by several ligatures, permitted this patient to return to work 15 days after operation without any further treatment. The patient no longer has any symptoms.

Super Learner Analysis of Electronic Adherence Data Improves Viral Prediction and May Provide Strategies for Selective HIV RNA Monitoring.

PubMed

Petersen, Maya L; LeDell, Erin; Schwab, Joshua; Sarovar, Varada; Gross, Robert; Reynolds, Nancy; Haberer, Jessica E; Goggin, Kathy; Golin, Carol; Arnsten, Julia; Rosen, Marc I; Remien, Robert H; Etoori, David; Wilson, Ira B; Simoni, Jane M; Erlen, Judith A; van der Laan, Mark J; Liu, Honghu; Bangsberg, David R

2015-05-01

Regular HIV RNA testing for all HIV-positive patients on antiretroviral therapy (ART) is expensive and has low yield since most tests are undetectable. Selective testing of those at higher risk of failure may improve efficiency. We investigated whether a novel analysis of adherence data could correctly classify virological failure and potentially inform a selective testing strategy. Multisite prospective cohort consortium. We evaluated longitudinal data on 1478 adult patients treated with ART and monitored using the Medication Event Monitoring System (MEMS) in 16 US cohorts contributing to the MACH14 consortium. Because the relationship between adherence and virological failure is complex and heterogeneous, we applied a machine-learning algorithm (Super Learner) to build a model for classifying failure and evaluated its performance using cross-validation. Application of the Super Learner algorithm to MEMS data, combined with data on CD4 T-cell counts and ART regimen, significantly improved classification of virological failure over a single MEMS adherence measure. Area under the receiver operating characteristic curve, evaluated on data not used in model fitting, was 0.78 (95% confidence interval: 0.75 to 0.80) and 0.79 (95% confidence interval: 0.76 to 0.81) for failure defined as single HIV RNA level >1000 copies per milliliter or >400 copies per milliliter, respectively. Our results suggest that 25%-31% of viral load tests could be avoided while maintaining sensitivity for failure detection at or above 95%, for a cost savings of $16-$29 per person-month. Our findings provide initial proof of concept for the potential use of electronic medication adherence data to reduce costs through behavior-driven HIV RNA testing.

Super learner analysis of electronic adherence data improves viral prediction and may provide strategies for selective HIV RNA monitoring

PubMed Central

Petersen, Maya L.; LeDell, Erin; Schwab, Joshua; Sarovar, Varada; Gross, Robert; Reynolds, Nancy; Haberer, Jessica E.; Goggin, Kathy; Golin, Carol; Arnsten, Julia; Rosen, Marc; Remien, Robert; Etoori, David; Wilson, Ira; Simoni, Jane M.; Erlen, Judith A.; van der Laan, Mark J.; Liu, Honghu; Bangsberg, David R

2015-01-01

Objective Regular HIV RNA testing for all HIV positive patients on antiretroviral therapy (ART) is expensive and has low yield since most tests are undetectable. Selective testing of those at higher risk of failure may improve efficiency. We investigated whether a novel analysis of adherence data could correctly classify virological failure and potentially inform a selective testing strategy. Design Multisite prospective cohort consortium. Methods We evaluated longitudinal data on 1478 adult patients treated with ART and monitored using the Medication Event Monitoring System (MEMS) in 16 United States cohorts contributing to the MACH14 consortium. Since the relationship between adherence and virological failure is complex and heterogeneous, we applied a machine-learning algorithm (Super Learner) to build a model for classifying failure and evaluated its performance using cross-validation. Results Application of the Super Learner algorithm to MEMS data, combined with data on CD4+ T cell counts and ART regimen, significantly improved classification of virological failure over a single MEMS adherence measure. Area under the ROC curve, evaluated on data not used in model fitting, was 0.78 (95% CI: 0.75, 0.80) and 0.79 (95% CI: 0.76, 0.81) for failure defined as single HIV RNA level >1000 copies/ml or >400 copies/ml, respectively. Our results suggest 25–31% of viral load tests could be avoided while maintaining sensitivity for failure detection at or above 95%, for a cost savings of $16–$29 per person-month. Conclusions Our findings provide initial proof-of-concept for the potential use of electronic medication adherence data to reduce costs through behavior-driven HIV RNA testing. PMID:25942462

Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure.

PubMed

Arnold, Amy C; Okamoto, Luis E; Gamboa, Alfredo; Black, Bonnie K; Raj, Satish R; Elijovich, Fernando; Robertson, David; Shibao, Cyndya A; Biaggioni, Italo

2016-02-01

Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that plasma angiotensin II is elevated and acts at AT1 (angiotensin type 1) receptors to contribute to hypertension in these patients. Because aldosterone and angiotensin II can also bind mineralocorticoid receptors to elevate blood pressure, we hypothesized that mineralocorticoid receptor activation plays a role in the hypertension of autonomic failure. To test this hypothesis, we determined the acute effects of the mineralocorticoid receptor antagonist eplerenone (50 mg, oral) versus placebo on supine blood pressure in a randomized, double-blind, crossover study. Medications were given at 8:00 pm with blood pressure recorded every 2 hours for 12 hours. Ten primary autonomic failure patients with supine hypertension completed this study (7 pure autonomic failure, 2 multiple system atrophy, 1 parkinson's disease; 7 male; 70±2 years of age). Eplerenone maximally reduced supine systolic blood pressure by 32±6 mm Hg at 8 hours after administration (versus 8±10 mm Hg placebo, P=0.016), with no effect on nocturia (12-hour urine volume: 985±134 mL placebo versus 931±94 mL eplerenone, P=0.492; nocturnal weight loss: -1.19±0.15 kg placebo versus -1.18±0.15 kg eplerenone, P=0.766). These findings suggest that inappropriate mineralocorticoid receptor activation contributes to the hypertension of autonomic failure, likely independent of canonical mineralocorticoid effects, and provides rationale for use of eplerenone in these patients. © 2015 American Heart Association, Inc.

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Determinants for undetected dementia and late-life depression.

PubMed

Chen, Ruoling; Hu, Zhi; Chen, Ruo-Li; Ma, Ying; Zhang, Dongmei; Wilson, Kenneth

2013-09-01

Determinants for undetected dementia and late-life depression have been not well studied. To investigate risk factors for undetected dementia and depression in older communities. Using the method of the 10/66 algorithm, we interviewed a random sample of 7072 participants aged ≥60 years in six provinces of China during 2007-2011. We documented doctor-diagnosed dementia and depression in the interview. Using the validated 10/66 algorithm we diagnosed dementia (n = 359) and depression (n = 328). We found that 93.1% of dementia and 92.5% of depression was undetected. Both undetected dementia and depression were significantly associated with low levels of education and occupation, and living in a rural area. The risk of undetected dementia was also associated with 'help available when needed', and inversely, with a family history of mental illness and having functional impairment. Undetected depression was significantly related to female gender, low income, having more children and inversely with having heart disease. Older adults in China have high levels of undetected dementia and depression. General socioeconomic improvement, associated with mental health education, targeting high-risk populations are likely to increase detection of dementia and depression in older adults, providing a backdrop for culturally acceptable service development.

A Bayesian hierarchical diffusion model decomposition of performance in Approach–Avoidance Tasks

PubMed Central

Krypotos, Angelos-Miltiadis; Beckers, Tom; Kindt, Merel; Wagenmakers, Eric-Jan

2015-01-01

Common methods for analysing response time (RT) tasks, frequently used across different disciplines of psychology, suffer from a number of limitations such as the failure to directly measure the underlying latent processes of interest and the inability to take into account the uncertainty associated with each individual's point estimate of performance. Here, we discuss a Bayesian hierarchical diffusion model and apply it to RT data. This model allows researchers to decompose performance into meaningful psychological processes and to account optimally for individual differences and commonalities, even with relatively sparse data. We highlight the advantages of the Bayesian hierarchical diffusion model decomposition by applying it to performance on Approach–Avoidance Tasks, widely used in the emotion and psychopathology literature. Model fits for two experimental data-sets demonstrate that the model performs well. The Bayesian hierarchical diffusion model overcomes important limitations of current analysis procedures and provides deeper insight in latent psychological processes of interest. PMID:25491372

The current and ideal state of anatomic pathology patient safety.

PubMed

Raab, Stephen Spencer

2014-01-01

An anatomic pathology diagnostic error may be secondary to a number of active and latent technical and/or cognitive components, which may occur anywhere along the total testing process in clinical and/or laboratory domains. For the pathologist interpretive steps of diagnosis, we examine Kahneman's framework of slow and fast thinking to explain different causes of error in precision (agreement) and in accuracy (truth). The pathologist cognitive diagnostic process involves image pattern recognition and a slow thinking error may be caused by the application of different rationally-constructed mental maps of image criteria/patterns by different pathologists. This type of error is partly related to a system failure in standardizing the application of these maps. A fast thinking error involves the flawed leap from image pattern to incorrect diagnosis. In the ideal state, anatomic pathology systems would target these cognitive error causes as well as the technical latent factors that lead to error.

Expansion of donor-derived hematopoietic stem cells with PIGA mutation associated with late graft failure after allogeneic stem cell transplantation.

PubMed

Mochizuki, Kanako; Sugimori, Chiharu; Qi, Zhirong; Lu, Xuzhang; Takami, Akiyoshi; Ishiyama, Ken; Kondo, Yukio; Yamazaki, Hirohito; Okumura, Hirokazu; Nakao, Shinji

2008-09-01

A small population of CD55(-)CD59(-) blood cells was detected in a patient who developed donor-type late graft failure after allogeneic stem cell transplantation (SCT) for treatment of aplastic anemia (AA). Chimerism and PIGA gene analyses showed the paroxysmal nocturnal hemoglobinuria (PNH)-type granulocytes to be of a donor-derived stem cell with a thymine insertion in PIGA exon 2. A sensitive mutation-specific polymerase chain reaction (PCR)-based analysis detected the mutation exclusively in DNA derived from the donor bone marrow (BM) cells. The patient responded to immunosuppressive therapy and achieved transfusion independence. The small population of PNH-type cells was undetectable in any of the 50 SCT recipients showing stable engraftment. The de novo development of donor cell-derived AA with a small population of PNH-type cells in this patient supports the concept that glycosyl phosphatidylinositol-anchored protein-deficient stem cells have a survival advantage in the setting of immune-mediated BM injury.

Modeling and characterization of partially inserted electrical connector faults

NASA Astrophysics Data System (ADS)

Tokgöz, ćaǧatay; Dardona, Sameh; Soldner, Nicholas C.; Wheeler, Kevin R.

2016-03-01

Faults within electrical connectors are prominent in avionics systems due to improper installation, corrosion, aging, and strained harnesses. These faults usually start off as undetectable with existing inspection techniques and increase in magnitude during the component lifetime. Detection and modeling of these faults are significantly more challenging than hard failures such as open and short circuits. Hence, enabling the capability to locate and characterize the precursors of these faults is critical for timely preventive maintenance and mitigation well before hard failures occur. In this paper, an electrical connector model based on a two-level nonlinear least squares approach is proposed. The connector is first characterized as a transmission line, broken into key components such as the pin, socket, and connector halves. Then, the fact that the resonance frequencies of the connector shift as insertion depth changes from a fully inserted to a barely touching contact is exploited. The model precisely captures these shifts by varying only two length parameters. It is demonstrated that the model accurately characterizes a partially inserted connector.

Digital Fly-By-Wire Flight Control Validation Experience

NASA Technical Reports Server (NTRS)

Szalai, K. J.; Jarvis, C. R.; Krier, G. E.; Megna, V. A.; Brock, L. D.; Odonnell, R. N.

1978-01-01

The experience gained in digital fly-by-wire technology through a flight test program being conducted by the NASA Dryden Flight Research Center in an F-8C aircraft is described. The system requirements are outlined, along with the requirements for flight qualification. The system is described, including the hardware components, the aircraft installation, and the system operation. The flight qualification experience is emphasized. The qualification process included the theoretical validation of the basic design, laboratory testing of the hardware and software elements, systems level testing, and flight testing. The most productive testing was performed on an iron bird aircraft, which used the actual electronic and hydraulic hardware and a simulation of the F-8 characteristics to provide the flight environment. The iron bird was used for sensor and system redundancy management testing, failure modes and effects testing, and stress testing in many cases with the pilot in the loop. The flight test program confirmed the quality of the validation process by achieving 50 flights without a known undetected failure and with no false alarms.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Structural Health Monitoring with Fiber Bragg Grating and Piezo Arrays

NASA Technical Reports Server (NTRS)

Black, Richard J.; Faridian, Ferey; Moslehi, Behzad; Sotoudeh, Vahid

2012-01-01

Structural health monitoring (SHM) is one of the most important tools available for the maintenance, safety, and integrity of aerospace structural systems. Lightweight, electromagnetic-interference- immune, fiber-optic sensor-based SHM will play an increasing role in more secure air transportation systems. Manufacturers and maintenance personnel have pressing needs for significantly improving safety and reliability while providing for lower inspection and maintenance costs. Undetected or untreated damage may grow and lead to catastrophic structural failure. Damage can originate from the strain/stress history of the material, imperfections of domain boundaries in metals, delamination in multi-layer materials, or the impact of machine tools in the manufacturing process. Damage can likewise develop during service life from wear and tear, or under extraordinary circumstances such as with unusual forces, temperature cycling, or impact of flying objects. Monitoring and early detection are key to preventing a catastrophic failure of structures, especially when these are expected to perform near their limit conditions.

Semicompeting risks in aging research: methods, issues and needs

PubMed Central

Varadhan, Ravi; Xue, Qian-Li; Bandeen-Roche, Karen

2015-01-01

A semicompeting risks problem involves two-types of events: a nonterminal and a terminal event (death). Typically, the nonterminal event is the focus of the study, but the terminal event can preclude the occurrence of the nonterminal event. Semicompeting risks are ubiquitous in studies of aging. Examples of semicompeting risk dyads include: dementia and death, frailty syndrome and death, disability and death, and nursing home placement and death. Semicompeting risk models can be divided into two broad classes: models based only on observables quantities (class O) and those based on potential (latent) failure times (class L). The classical illness-death model belongs to class O. This model is a special case of the multistate models, which has been an active area of methodology development. During the past decade and a half, there has also been a flurry of methodological activity on semicompeting risks based on latent failure times (L models). These advances notwithstanding, the semi-competing risks methodology has not penetrated biomedical research, in general, and gerontological research, in particular. Some possible reasons for this lack of uptake are: the methods are relatively new and sophisticated, conceptual problems associated with potential failure time models are difficult to overcome, paucity of expository articles aimed at educating practitioners, and non-availability of readily usable software. The main goals of this review article are: (i) to describe the major types of semicompeting risks problems arising in aging research, (ii) to provide a brief survey of the semicompeting risks methods, (iii) to suggest appropriate methods for addressing the problems in aging research, (iv) to highlight areas where more work is needed, and (v) to suggest ways to facilitate the uptake of the semicompeting risks methodology by the broader biomedical research community. PMID:24729136

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

A novel deletion in the thyrotropin Beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey.

PubMed

Hermanns, Pia; Couch, Robert; Leonard, Norma; Klotz, Cherise; Pohlenz, Joachim

2014-01-01

Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability. We describe a boy with ICCH due to a large homozygous TSHβ gene deletion. A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene. Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.

The large intestine as a major reservoir for simian immunodeficiency virus in macaques with long-term, nonprogressing infection.

PubMed

Ling, Binhua; Mohan, Mahesh; Lackner, Andrew A; Green, Linda C; Marx, Preston A; Doyle, Lara A; Veazey, Ronald S

2010-12-15

Although patients with human immunodeficiency virus type 1 infection who are receiving antiretroviral therapy and those with long-term, nonprogressive infection (LTNPs) usually have undetectable viremia, virus persists in tissue reservoirs throughout infection. However, the distribution and magnitude of viral persistence and replication in tissues has not been adequately examined. Here, we used the simian immunodeficiency virus (SIV) macaque model to quantify and compare viral RNA and DNA in the small (jejunum) and large (colon) intestine of LTNPs. In LTNPs with chronic infection, the colon had consistently higher viral levels than did the jejunum. The colon also had higher percentages of viral target cells (memory CD4(+) CCR5(+) T cells) and proliferating memory CD4(+) T cells than did the jejunum, whereas markers of cell activation were comparable in both compartments. These data indicate that the large intestine is a major viral reservoir in LTNPs, which may be the result of persistent, latently infected cells and higher turnover of naive and central memory CD4(+) T cells in this major immunologic compartment.

Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests

PubMed Central

2013-01-01

Background An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens. Methods PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined. Results Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ≤0.005% or ≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker’s regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ≤250 parasites/μl (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046). Conclusion In the present work, 10.7% of the isolates with a parasitaemia ≤0.005% (≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker’model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2. PMID:23347727

A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

PubMed

Braun, Dominique L; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

2015-01-01

The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious adverse events and no significant drug-drug interactions were associated with silibinin. A lead-in with silibinin before triple-therapy was safe and highly effective in difficult-to-treat HIV/HCV coinfected patients, with a pronounced HCV-RNA decline during the lead-in phase, which translates into 63% SVR. An add-on of intravenous silibinin to standard of care HCV treatment is worth further exploration in selected difficult-to-treat patients. ClinicalTrials.gov NCT01816490.

Adaptive optimisation-offline cyber attack on remote state estimator

NASA Astrophysics Data System (ADS)

Huang, Xin; Dong, Jiuxiang

2017-10-01

Security issues of cyber-physical systems have received increasing attentions in recent years. In this paper, deception attacks on the remote state estimator equipped with the chi-squared failure detector are considered, and it is assumed that the attacker can monitor and modify all the sensor data. A novel adaptive optimisation-offline cyber attack strategy is proposed, where using the current and previous sensor data, the attack can yield the largest estimation error covariance while ensuring to be undetected by the chi-squared monitor. From the attacker's perspective, the attack is better than the existing linear deception attacks to degrade the system performance. Finally, some numerical examples are provided to demonstrate theoretical results.

Three Cs in Measurement Models: Causal Indicators, Composite Indicators, and Covariates

PubMed Central

Bollen, Kenneth A.; Bauldry, Shawn

2013-01-01

In the last two decades attention to causal (and formative) indicators has grown. Accompanying this growth has been the belief that we can classify indicators into two categories, effect (reflective) indicators and causal (formative) indicators. This paper argues that the dichotomous view is too simple. Instead, there are effect indicators and three types of variables on which a latent variable depends: causal indicators, composite (formative) indicators, and covariates (the “three Cs”). Causal indicators have conceptual unity and their effects on latent variables are structural. Covariates are not concept measures, but are variables to control to avoid bias in estimating the relations between measures and latent variable(s). Composite (formative) indicators form exact linear combinations of variables that need not share a concept. Their coefficients are weights rather than structural effects and composites are a matter of convenience. The failure to distinguish the “three Cs” has led to confusion and questions such as: are causal and formative indicators different names for the same indicator type? Should an equation with causal or formative indicators have an error term? Are the coefficients of causal indicators less stable than effect indicators? Distinguishing between causal and composite indicators and covariates goes a long way toward eliminating this confusion. We emphasize the key role that subject matter expertise plays in making these distinctions. We provide new guidelines for working with these variable types, including identification of models, scaling latent variables, parameter estimation, and validity assessment. A running empirical example on self-perceived health illustrates our major points. PMID:21767021

Deciphering the enigma of undetected species, phylogenetic, and functional diversity based on Good-Turing theory.

PubMed

Chao, Anne; Chiu, Chun-Huo; Colwell, Robert K; Magnago, Luiz Fernando S; Chazdon, Robin L; Gotelli, Nicholas J

2017-11-01

Estimating the species, phylogenetic, and functional diversity of a community is challenging because rare species are often undetected, even with intensive sampling. The Good-Turing frequency formula, originally developed for cryptography, estimates in an ecological context the true frequencies of rare species in a single assemblage based on an incomplete sample of individuals. Until now, this formula has never been used to estimate undetected species, phylogenetic, and functional diversity. Here, we first generalize the Good-Turing formula to incomplete sampling of two assemblages. The original formula and its two-assemblage generalization provide a novel and unified approach to notation, terminology, and estimation of undetected biological diversity. For species richness, the Good-Turing framework offers an intuitive way to derive the non-parametric estimators of the undetected species richness in a single assemblage, and of the undetected species shared between two assemblages. For phylogenetic diversity, the unified approach leads to an estimator of the undetected Faith's phylogenetic diversity (PD, the total length of undetected branches of a phylogenetic tree connecting all species), as well as a new estimator of undetected PD shared between two phylogenetic trees. For functional diversity based on species traits, the unified approach yields a new estimator of undetected Walker et al.'s functional attribute diversity (FAD, the total species-pairwise functional distance) in a single assemblage, as well as a new estimator of undetected FAD shared between two assemblages. Although some of the resulting estimators have been previously published (but derived with traditional mathematical inequalities), all taxonomic, phylogenetic, and functional diversity estimators are now derived under the same framework. All the derived estimators are theoretically lower bounds of the corresponding undetected diversities; our approach reveals the sufficient conditions under which the estimators are nearly unbiased, thus offering new insights. Simulation results are reported to numerically verify the performance of the derived estimators. We illustrate all estimators and assess their sampling uncertainty with an empirical dataset for Brazilian rain forest trees. These estimators should be widely applicable to many current problems in ecology, such as the effects of climate change on spatial and temporal beta diversity and the contribution of trait diversity to ecosystem multi-functionality. © 2017 by the Ecological Society of America.

Composite Bending Box Section Modal Vibration Fault Detection

NASA Technical Reports Server (NTRS)

Werlink, Rudy

2002-01-01

One of the primary concerns with Composite construction in critical structures such as wings and stabilizers is that hidden faults and cracks can develop operationally. In the real world, catastrophic sudden failure can result from these undetected faults in composite structures. Vibration data incorporating a broad frequency modal approach, could detect significant changes prior to failure. The purpose of this report is to investigate the usefulness of frequency mode testing before and after bending and torsion loading on a composite bending Box Test section. This test article is representative of construction techniques being developed for the recent NASA Blended Wing Body Low Speed Vehicle Project. The Box section represents the construction technique on the proposed blended wing aircraft. Modal testing using an impact hammer provides an frequency fingerprint before and after bending and torsional loading. If a significant structural discontinuity develops, the vibration response is expected to change. The limitations of the data will be evaluated for future use as a non-destructive in-situ method of assessing hidden damage in similarly constructed composite wing assemblies. Modal vibration fault detection sensitivity to band-width, location and axis will be investigated. Do the sensor accelerometers need to be near the fault and or in the same axis? The response data used in this report was recorded at 17 locations using tri-axial accelerometers. The modal tests were conducted following 5 independent loading conditions before load to failure and 2 following load to failure over a period of 6 weeks. Redundant data was used to minimize effects from uncontrolled variables which could lead to incorrect interpretations. It will be shown that vibrational modes detected failure at many locations when skin de-bonding failures occurred near the center section. Important considerations are the axis selected and frequency range.

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

PubMed Central

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

2018-01-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64–0.76) to 0.82 (95% CI 0.78–0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70–0.81) to 0.89 (95% CI 0.86–0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure. PMID:29327942

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

PubMed

Kievit, Rogier F; Gohar, Aisha; Hoes, Arno W; Bots, Michiel L; van Riet, Evelien Es; van Mourik, Yvonne; Bertens, Loes Cm; Boonman-de Winter, Leandra Jm; den Ruijter, Hester M; Rutten, Frans H

2018-03-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64-0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86-0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

Process-based quality management for clinical implementation of adaptive radiotherapy

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

Noel, Camille E.; Santanam, Lakshmi; Parikh, Parag J.

Purpose: Intensity-modulated adaptive radiotherapy (ART) has been the focus of considerable research and developmental work due to its potential therapeutic benefits. However, in light of its unique quality assurance (QA) challenges, no one has described a robust framework for its clinical implementation. In fact, recent position papers by ASTRO and AAPM have firmly endorsed pretreatment patient-specific IMRT QA, which limits the feasibility of online ART. The authors aim to address these obstacles by applying failure mode and effects analysis (FMEA) to identify high-priority errors and appropriate risk-mitigation strategies for clinical implementation of intensity-modulated ART. Methods: An experienced team of twomore » clinical medical physicists, one clinical engineer, and one radiation oncologist was assembled to perform a standard FMEA for intensity-modulated ART. A set of 216 potential radiotherapy failures composed by the forthcoming AAPM task group 100 (TG-100) was used as the basis. Of the 216 failures, 127 were identified as most relevant to an ART scheme. Using the associated TG-100 FMEA values as a baseline, the team considered how the likeliness of occurrence (O), outcome severity (S), and likeliness of failure being undetected (D) would change for ART. New risk priority numbers (RPN) were calculated. Failures characterized by RPN ≥ 200 were identified as potentially critical. Results: FMEA revealed that ART RPN increased for 38% (n = 48/127) of potential failures, with 75% (n = 36/48) attributed to failures in the segmentation and treatment planning processes. Forty-three of 127 failures were identified as potentially critical. Risk-mitigation strategies include implementing a suite of quality control and decision support software, specialty QA software/hardware tools, and an increase in specially trained personnel. Conclusions: Results of the FMEA-based risk assessment demonstrate that intensity-modulated ART introduces different (but not necessarily more) risks than standard IMRT and may be safely implemented with the proper mitigations.« less

Process-based quality management for clinical implementation of adaptive radiotherapy

PubMed Central

Noel, Camille E.; Santanam, Lakshmi; Parikh, Parag J.; Mutic, Sasa

2014-01-01

Purpose: Intensity-modulated adaptive radiotherapy (ART) has been the focus of considerable research and developmental work due to its potential therapeutic benefits. However, in light of its unique quality assurance (QA) challenges, no one has described a robust framework for its clinical implementation. In fact, recent position papers by ASTRO and AAPM have firmly endorsed pretreatment patient-specific IMRT QA, which limits the feasibility of online ART. The authors aim to address these obstacles by applying failure mode and effects analysis (FMEA) to identify high-priority errors and appropriate risk-mitigation strategies for clinical implementation of intensity-modulated ART. Methods: An experienced team of two clinical medical physicists, one clinical engineer, and one radiation oncologist was assembled to perform a standard FMEA for intensity-modulated ART. A set of 216 potential radiotherapy failures composed by the forthcoming AAPM task group 100 (TG-100) was used as the basis. Of the 216 failures, 127 were identified as most relevant to an ART scheme. Using the associated TG-100 FMEA values as a baseline, the team considered how the likeliness of occurrence (O), outcome severity (S), and likeliness of failure being undetected (D) would change for ART. New risk priority numbers (RPN) were calculated. Failures characterized by RPN ≥ 200 were identified as potentially critical. Results: FMEA revealed that ART RPN increased for 38% (n = 48/127) of potential failures, with 75% (n = 36/48) attributed to failures in the segmentation and treatment planning processes. Forty-three of 127 failures were identified as potentially critical. Risk-mitigation strategies include implementing a suite of quality control and decision support software, specialty QA software/hardware tools, and an increase in specially trained personnel. Conclusions: Results of the FMEA-based risk assessment demonstrate that intensity-modulated ART introduces different (but not necessarily more) risks than standard IMRT and may be safely implemented with the proper mitigations. PMID:25086527

Process-based quality management for clinical implementation of adaptive radiotherapy.

PubMed

Noel, Camille E; Santanam, Lakshmi; Parikh, Parag J; Mutic, Sasa

2014-08-01

Intensity-modulated adaptive radiotherapy (ART) has been the focus of considerable research and developmental work due to its potential therapeutic benefits. However, in light of its unique quality assurance (QA) challenges, no one has described a robust framework for its clinical implementation. In fact, recent position papers by ASTRO and AAPM have firmly endorsed pretreatment patient-specific IMRT QA, which limits the feasibility of online ART. The authors aim to address these obstacles by applying failure mode and effects analysis (FMEA) to identify high-priority errors and appropriate risk-mitigation strategies for clinical implementation of intensity-modulated ART. An experienced team of two clinical medical physicists, one clinical engineer, and one radiation oncologist was assembled to perform a standard FMEA for intensity-modulated ART. A set of 216 potential radiotherapy failures composed by the forthcoming AAPM task group 100 (TG-100) was used as the basis. Of the 216 failures, 127 were identified as most relevant to an ART scheme. Using the associated TG-100 FMEA values as a baseline, the team considered how the likeliness of occurrence (O), outcome severity (S), and likeliness of failure being undetected (D) would change for ART. New risk priority numbers (RPN) were calculated. Failures characterized by RPN ≥ 200 were identified as potentially critical. FMEA revealed that ART RPN increased for 38% (n = 48/127) of potential failures, with 75% (n = 36/48) attributed to failures in the segmentation and treatment planning processes. Forty-three of 127 failures were identified as potentially critical. Risk-mitigation strategies include implementing a suite of quality control and decision support software, specialty QA software/hardware tools, and an increase in specially trained personnel. Results of the FMEA-based risk assessment demonstrate that intensity-modulated ART introduces different (but not necessarily more) risks than standard IMRT and may be safely implemented with the proper mitigations.

Impact of fulminant hepatic failure in C-reactive protein?

PubMed

Silvestre, Joana Pedro da Silva; Coelho, Luis Miguel da Cruz; Póvoa, Pedro Manuel Sarmento Rodrigues

2010-12-01

Fulminant hepatic failure (FHF) refers to the rapid development of severe acute liver injury with impaired synthetic function, coagulopathy, and encephalopathy in a person who previously had a normal liver or had a well-compensated liver disease. It is a rare complication in critically ill patients and carries a very bad prognosis. Serum C-reactive protein (CRP), a useful marker of infection, is produced exclusively by the liver. The aim of this study was to assess CRP concentrations in patients with FHF. We prospectively identified patients with sepsis and FHF treated at the intensive care unit (ICU). Data collected included admission diagnosis, medical history, systemic inflammatory response syndrome criteria, Acute Physiologic and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores. C-reactive protein and white cell count were measured at admission and then daily until ICU discharge. We included 7 patients with FHF and sepsis. Six patients died with severe multiple organ failure. Six patients were already admitted with FHF, with the remaining one being diagnosed at the 26th day of ICU stay. All patients present severe coagulopathy. In all septic patients, despite clinical deterioration, CRP levels were markedly decreased sometimes reaching undetectable levels. In septic patients with FHF, CRP is more a marker of severe liver dysfunction and should not be used as a marker of infection. As a result, in a patient admitted with a very high suspicion of infection and an abnormally low CRP concentration or with a marked CRP decline despite persistent septic shock, severe hepatic failure should be ruled out. Copyright © 2010 Elsevier Inc. All rights reserved.

NASA flight electronics environmental stress screening survey

NASA Technical Reports Server (NTRS)

Marian, E. J. (Compiler)

1983-01-01

Data compiled by the Institute of Environmental Sciences were used to establish guidelines for identifying defective, abnormal, or marginal parts as well as manufacturing defects. These data are augmented with other available sources of similar information in conjunction with NASA centers' data and presented in a form that may be useful to all NASA centers in planning and developing effective environmental stress screens. Information relative to thermal and vibration screens as the most effective methods for surfacing latent failures in electronic equipment at the component level is considered.

A Cross-Cultural Comparison of Symptom Reporting and Symptom Clusters in Heart Failure.

PubMed

Park, Jumin; Johantgen, Mary E

2017-07-01

An understanding of symptoms in heart failure (HF) among different cultural groups has become increasingly important. The purpose of this study was to compare symptom reporting and symptom clusters in HF patients between a Western (the United States) and an Eastern Asian sample (China and Taiwan). A secondary analysis of a cross-sectional observational study was conducted. The data were obtained from a matched HF patient sample from the United States and China/Taiwan ( N = 240 in each). Eight selective items related to HF symptoms from the Minnesota Living with Heart Failure Questionnaire were analyzed. Compared with the U.S. sample, HF patients from China/Taiwan reported a lower level of symptom distress. Analysis of two different regional groups did not result in the same number of clusters using latent class approach: the United States (four classes) and China/Taiwan (three classes). The study demonstrated that symptom reporting and identification of symptom clusters might be influenced by cultural factors.

Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.

PubMed

Hussein, Ayman A; Bartz, Traci M; Gottdiener, John S; Sotoodehnia, Nona; Heckbert, Susan R; Lloyd-Jones, Donald; Kizer, Jorge R; Christenson, Robert; Wazni, Oussama; deFilippi, Christopher

2015-05-01

Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset. The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF). In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses. Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF. The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment.

PubMed

Abdelrahman, Tamer; Hughes, Joseph; Main, Janice; McLauchlan, John; Thursz, Mark; Thomson, Emma

2015-01-01

High rates of sexually transmitted infection and reinfection with hepatitis C virus (HCV) have recently been reported in human immunodeficiency virus (HIV)-infected men who have sex with men and reinfection has also been described in monoinfected injecting drug users. The diagnosis of reinfection has traditionally been based on direct Sanger sequencing of samples pre- and posttreatment, but not on more sensitive deep sequencing techniques. We studied viral quasispecies dynamics in patients who failed standard of care therapy in a high-risk HIV-infected cohort of patients with early HCV infection to determine whether treatment failure was associated with reinfection or recrudescence of preexisting infection. Paired sequences (pre- and posttreatment) were analyzed. The HCV E2 hypervariable region-1 was amplified using nested reverse-transcription polymerase chain reaction (RT-PCR) with indexed genotype-specific primers and the same products were sequenced using both Sanger and 454 pyrosequencing approaches. Of 99 HIV-infected patients with acute HCV treated with 24-48 weeks of pegylated interferon alpha and ribavirin, 15 failed to achieve a sustained virological response (six relapsed, six had a null response, and three had a partial response). Using direct sequencing, 10/15 patients (66%) had evidence of a previously undetected strain posttreatment; in many studies, this is interpreted as reinfection. However, pyrosequencing revealed that 15/15 (100%) of patients had evidence of persisting infection; 6/15 (40%) patients had evidence of a previously undetected variant present in the posttreatment sample in addition to a variant that was detected at baseline. This could represent superinfection or a limitation of the sensitivity of pyrosequencing. In this high-risk group, the emergence of new viral strains following treatment failure is most commonly associated with emerging dominance of preexisting minority variants rather than reinfection. Superinfection may occur in this cohort but reinfection is overestimated by Sanger sequencing. © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.

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

Wijesooriya, K; Seitter, K; Desai, V

Purpose: To present our single institution experience on catching errors with trajectory log file analysis. The reported causes of failures, probability of occurrences (O), severity of effects (S), and the probability of the failures to be undetected (D) could be added to guidelines of FMEA analysis. Methods: From March 2013 to March 2014, 19569 patient treatment fields/arcs were analyzed. This work includes checking all 131 treatment delivery parameters for all patients, all treatment sites and all treatment delivery fractions. TrueBeam trajectory log files for all treatment field types as well as all imaging types were accessed, read in every 20ms,more » and every control point (total of 37 million parameters) compared to the physician approved plan in the planning system. Results: Couch angle outlier occurrence: N= 327, range = −1.7 −1.2 deg; gantry angle outlier occurrence: N =59, range = 0.09 – 5.61 deg, collimator angle outlier occurrence: N = 13, range = −0.2 – 0.2 deg. VMAT cases have slightly larger variations in mechanical parameters. MLC: 3D single control point fields have a maximum deviation of 0.04 mm, 39 step and shoot IMRT cases have MLC −0.3 – 0.5 mm deviations, all (1286) VMAT cases have −0.9 – 0.7 mm deviations. Two possible serious errors were found: 1) A 4 cm isocenter shift for the PA beam of an AP-PA pair, under-dosing a portion of PTV by 25%. 2) Delivery with MLC leaves abutted behind the jaws as opposed to the midline as planned, leading to a under-dosing of a small volume of the PTV by 25%, by just the boost plan. Due to their error origin, neither of these errors could have been detected by pre-treatment verification. Conclusion: Performing Trajectory Log file analysis could catch typically undetected errors to avoid potentially adverse incidents.« less

Crack detection and fatigue related delamination in FRP composites applied to concrete

NASA Astrophysics Data System (ADS)

Brown, Jeff; Baker, Rebecca; Kallemeyn, Lisa; Zendler, Andrew

2008-03-01

Reinforced concrete beams are designed to allow minor concrete cracking in the tension zone. The severity of cracking in a beam element is a good indicator of how well a structure is performing and whether or not repairs are needed to prevent structural failure. FRP composites are commonly used to increase the flexural and shear capacity of RC beam elements, but one potential disadvantage of this method is that strengthened surfaces are no longer visible and cracks or delaminations that result from excessive loading or fatigue may go undetected. This research investigated thermal imaging techniques for detecting load induced cracking in the concrete substrate and delamination of FRP strengthening systems applied to reinforced concrete (RC). One small-scale RC beam (5 in. x 6 in. x 60 in.) was strengthened with FRP and loaded to failure monotonically. An infrared thermography inspection was performed after failure. A second strengthened beam was loaded cyclically for 1,750,000 cycles to investigate how fatigue might affect substrate cracking and delamination growth throughout the service-life of a repaired element. No changes were observed in the FRP bond during/after the cyclic loading. The thermal imaging component of this research included pixel normalization to enhance detectability and characterization of this specific type of damage.

[Polio vaccination failure in Italy, years 2006-2010].

PubMed

Iannazzo, Stefania; Rizzuto, Elvira; Pompa, Maria Grazia

2014-01-01

The purpose of this paper is to describe the lack of antipolio vaccination and its reasons, in the period 2006-2010. STUDY DESIGN, SETTING AND PARTICIPANTS. Until 2014 the data on vaccination activities, aggregated at the regional level, were sent to the Ministry of Health using a paper form used to collect the data and then to calculate vaccine coverage (CV) at 24 months. This form contains a section for identifying the reasons for polio vaccination failure. During the reporting period the national CV was always above 95%. The highest rates of non-vaccination were always observed in the same Region. Polio vaccination failure is well explained in 82%of cases, but only three Regions have always provided an explanation, while two have extremely low percentages of explanation, less than 50%. The dominant mode is «noncompliant » (45.5%), followed by «undetectable» (26.5%). The percentage of explanation of non-vaccination was lower than expected. At the moment we cannot clarify why, but only speculate that the lack of a computerized immunization registry has been a key element. Probably, the form used was not sufficiently detailed to monitor the phenomenon of non-vaccination and program interventions. Updating the form, in 2013, we took into account these and other critical issues.

Nonexplicit change detection in complex dynamic settings: what eye movements reveal.

PubMed

Vachon, François; Vallières, Benoît R; Jones, Dylan M; Tremblay, Sébastien

2012-12-01

We employed a computer-controlled command-and-control (C2) simulation and recorded eye movements to examine the extent and nature of the inability to detect critical changes in dynamic displays when change detection is implicit (i.e., requires no explicit report) to the operator's task. Change blindness-the failure to notice significant changes to a visual scene-may have dire consequences on performance in C2 and surveillance operations. Participants performed a radar-based risk-assessment task involving multiple subtasks. Although participants were not required to explicitly report critical changes to the operational display, change detection was critical in informing decision making. Participants' eye movements were used as an index of visual attention across the display. Nonfixated (i.e., unattended) changes were more likely to be missed than were fixated (i.e., attended) changes, supporting the idea that focused attention is necessary for conscious change detection. The finding of significant pupil dilation for changes undetected but fixated suggests that attended changes can nonetheless be missed because of a failure of attentional processes. Change blindness in complex dynamic displays takes the form of failures in establishing task-appropriate patterns of attentional allocation. These findings have implications in the design of change-detection support tools for dynamic displays and work procedure in C2 and surveillance.

Prevalence of Three-Rooted Mandibular First Molars among Indians Using SCT

PubMed Central

Garg, Amit Kumar; Tewari, Rajendra Kumar; Agrawal, Neha

2013-01-01

Undetected extra roots or root canals are a major reason for failure of endodontic treatment. Failure to recognize an extra distolingual (DL) root in mandibular first molar may lead to incomplete debridement of the root canal system and eventually treatment failure. Therefore, it is crucial that atypical anatomy is identified before and during dental treatment. Spiral computed tomography (SCT) images can show 3D images, and therefore much detail can be used when traditional methods prevent adequate endodontic treatment. The overall incidence of DL roots on the mandibular first molars was 6.40% for all patients and 5.00% for all teeth, respectively. The occurrence of DL roots on the right side and on the left side showed a statistically significant difference. The bilateral incidence of symmetrical distribution of DL roots was 56.25%. The DL root canal orifice was separated from DB canal orifice by 2.79 ± 0.34 mm, from the MB canal orifice by 4.23 ± 0.81 mm, and from the ML canal orifice by 3.29 ± 0.52 mm. The high prevalence of the DL root in permanent mandibular first molars among the Indian population by using SCT and estimations of the interorifice distance of such teeth might be useful for successful endodontic treatments. PMID:23840212

Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study

PubMed Central

Rodríguez, Manuel; Pascasio, Juan Manuel; Fraga, Enrique; Fuentes, Javier; Prieto, Martín; Sánchez-Antolín, Gloria; Calleja, José Luis; Molina, Esther; García-Buey, María Luisa; Blanco, María Ángeles; Salmerón, Javier; Bonet, María Lucía; Pons, José Antonio; González, José Manuel; Casado, Miguel Ángel; Jorquera, Francisco; Group, the TENOSIMP-B Research

2017-01-01

AIM To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM. METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed. RESULTS Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001). CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs. PMID:29151700

Impact of Undetected Comorbidity on Treatment and Outcomes of Breast Cancer

PubMed Central

Griffiths, Robert I.; Gleeson, Michelle L.; Valderas, José M.; Danese, Mark D.

2014-01-01

Preexisting comorbidity adversely impacts breast cancer treatment and outcomes. We examined the incremental impact of comorbidity undetected until cancer. We followed breast cancer patients in SEER-Medicare from 12 months before to 84 months after diagnosis. Two comorbidity indices were constructed: the National Cancer Institute index, using 12 months of claims before cancer, and a second index for previously undetected conditions, using three months after cancer. Conditions present in the first were excluded from the second. Overall, 6,184 (10.1%) had ≥1 undetected comorbidity. Chronic obstructive pulmonary disease (38%) was the most common undetected condition. In multivariable analyses that adjusted for comorbidity detected before cancer, older age, later stage, higher grade, and poor performance status all were associated with higher odds of ≥1 undetected comorbidity. In stage I–III cancer, undetected comorbidity was associated with lower adjusted odds of receiving adjuvant chemotherapy (Odds Ratio (OR) = 0.81, 95% Confidence Interval (CI) 0.73–0.90, P < 0.0001; OR = 0.38, 95% CI 0.30–0.49, P < 0.0001; index score 1 or ≥2, respectively), and with increased mortality (Hazard Ratio (HR) = 1.45, 95% CI 1.38–1.53, P < 0.0001; HR = 2.38, 95% CI 2.18–2.60, P < 0.0001; index score 1 or ≥2). Undetected comorbidity is associated with less aggressive treatment and higher mortality in breast cancer. PMID:24688795

Acoustic Emission Analysis of Prestressed Concrete Structures

NASA Astrophysics Data System (ADS)

Elfergani, H. A.; Pullin, R.; Holford, K. M.

2011-07-01

Corrosion is a substantial problem in numerous structures and in particular corrosion is very serious in reinforced and prestressed concrete and must, in certain applications, be given special consideration because failure may result in loss of life and high financial cost. Furthermore corrosion cannot only be considered a long term problem with many studies reporting failure of bridges and concrete pipes due to corrosion within a short period after they were constructed. The concrete pipes which transport water are examples of structures that have suffered from corrosion; for example, the pipes of The Great Man-Made River Project of Libya. Five pipe failures due to corrosion have occurred since their installation. The main reason for the damage is corrosion of prestressed wires in the pipes due to the attack of chloride ions from the surrounding soil. Detection of the corrosion in initial stages has been very important to avoid other failures and the interruption of water flow. Even though most non-destructive methods which are used in the project are able to detect wire breaks, they cannot detect the presence of corrosion. Hence in areas where no excavation has been completed, areas of serious damage can go undetected. Therefore, the major problem which faces engineers is to find the best way to detect the corrosion and prevent the pipes from deteriorating. This paper reports on the use of the Acoustic Emission (AE) technique to detect the early stages of corrosion prior to deterioration of concrete structures.

Progress of a Cross-Correlation Based Optical Strain Measurement Technique for Detecting Radial Growth on a Rotating Disk

NASA Technical Reports Server (NTRS)

Clem, Michelle M.; Abdul-Aziz, Ali; Woike, Mark R.; Fralick, Gustave C.

2015-01-01

The modern turbine engine operates in a harsh environment at high speeds and is repeatedly exposed to combined high mechanical and thermal loads. The cumulative effects of these external forces lead to high stresses and strains on the engine components, such as the rotating turbine disks, which may eventually lead to a catastrophic failure if left undetected. The operating environment makes it difficult to use conventional strain gauges, therefore, non-contact strain measurement techniques is of interest to NASA and the turbine engine community. This presentation describes one such approach; the use of cross correlation analysis to measure strain experienced by the engine turbine disk with the goal of assessing potential faults and damage.

Executive summary of the GESIDA/National AIDS Plan Consensus Document on Antiretroviral Therapy in Adults Infected by the Human Immunodeficiency Virus (Updated January 2016).

PubMed

2016-01-01

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (NRTI), and 1 drug from another family. Four of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further 6 regimens, which are based on an INSTI, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with cobicistat or ritonavir (PI/COBI, PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include 3 (or at least 2) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

PubMed

Reissig, Kathrin; Silver, Andrew; Hartig, Roland; Schinlauer, Antje; Walluscheck, Diana; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert; Poehlmann-Nitsche, Angela

2017-01-01

Dysregulation of c-Jun N -terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Understanding Human Error in Naval Aviation Mishaps.

PubMed

Miranda, Andrew T

2018-04-01

To better understand the external factors that influence the performance and decisions of aviators involved in Naval aviation mishaps. Mishaps in complex activities, ranging from aviation to nuclear power operations, are often the result of interactions between multiple components within an organization. The Naval aviation mishap database contains relevant information, both in quantitative statistics and qualitative reports, that permits analysis of such interactions to identify how the working atmosphere influences aviator performance and judgment. Results from 95 severe Naval aviation mishaps that occurred from 2011 through 2016 were analyzed using Bayes' theorem probability formula. Then a content analysis was performed on a subset of relevant mishap reports. Out of the 14 latent factors analyzed, the Bayes' application identified 6 that impacted specific aspects of aviator behavior during mishaps. Technological environment, misperceptions, and mental awareness impacted basic aviation skills. The remaining 3 factors were used to inform a content analysis of the contextual information within mishap reports. Teamwork failures were the result of plan continuation aggravated by diffused responsibility. Resource limitations and risk management deficiencies impacted judgments made by squadron commanders. The application of Bayes' theorem to historical mishap data revealed the role of latent factors within Naval aviation mishaps. Teamwork failures were seen to be considerably damaging to both aviator skill and judgment. Both the methods and findings have direct application for organizations interested in understanding the relationships between external factors and human error. It presents real-world evidence to promote effective safety decisions.

Induction motor inter turn fault detection using infrared thermographic analysis

NASA Astrophysics Data System (ADS)

Singh, Gurmeet; Anil Kumar, T. Ch.; Naikan, V. N. A.

2016-07-01

Induction motors are the most commonly used prime movers in industries. These are subjected to various environmental, thermal and load stresses that ultimately reduces the motor efficiency and later leads to failure. Inter turn fault is the second most commonly observed faults in the motors and is considered the most severe. It can lead to the failure of complete phase and can even cause accidents, if left undetected or untreated. This paper proposes an online and non invasive technique that uses infrared thermography, in order to detect the presence of inter turn fault in induction motor drive. Two methods have been proposed that detect the fault and estimate its severity. One method uses transient thermal monitoring during the start of motor and other applies pseudo coloring technique on infrared image of the motor, after it reaches a thermal steady state. The designed template for pseudo-coloring is in acquiescence with the InterNational Electrical Testing Association (NETA) thermographic standard. An index is proposed to assess the severity of the fault present in the motor.

Signals for glucagon secretion.

PubMed

Bloom, S R

1977-01-01

The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.

Resistance Analyses of Integrase Strand Transfer Inhibitors within Phase 3 Clinical Trials of Treatment-Naive Patients

PubMed Central

White, Kirsten L.; Raffi, Francois; Miller, Michael D.

2014-01-01

The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens has attained remarkably high levels, reaching undetectable viral loads in 90% of patients by Week 48; however, there remain patients who require a change in regimen due to adverse events, virologic failure with emergent resistance or other issues of patient management. Large, randomized clinical trials conducted in antiretroviral treatment-naive individuals are required for drug approval in this population in the US, EU and other countries, with the primary endpoint for virologic success at Week 48. However, there are differences in the definition of virologic failure and the evaluation of drug resistance among the trials. This review focuses on the methodology and tabulation of resistance to INSTIs in phase 3 clinical trials of first-line regimens and discusses case studies of resistance. PMID:25054884

Defect-Repairable Latent Feature Extraction of Driving Behavior via a Deep Sparse Autoencoder

PubMed Central

Taniguchi, Tadahiro; Takenaka, Kazuhito; Bando, Takashi

2018-01-01

Data representing driving behavior, as measured by various sensors installed in a vehicle, are collected as multi-dimensional sensor time-series data. These data often include redundant information, e.g., both the speed of wheels and the engine speed represent the velocity of the vehicle. Redundant information can be expected to complicate the data analysis, e.g., more factors need to be analyzed; even varying the levels of redundancy can influence the results of the analysis. We assume that the measured multi-dimensional sensor time-series data of driving behavior are generated from low-dimensional data shared by the many types of one-dimensional data of which multi-dimensional time-series data are composed. Meanwhile, sensor time-series data may be defective because of sensor failure. Therefore, another important function is to reduce the negative effect of defective data when extracting low-dimensional time-series data. This study proposes a defect-repairable feature extraction method based on a deep sparse autoencoder (DSAE) to extract low-dimensional time-series data. In the experiments, we show that DSAE provides high-performance latent feature extraction for driving behavior, even for defective sensor time-series data. In addition, we show that the negative effect of defects on the driving behavior segmentation task could be reduced using the latent features extracted by DSAE. PMID:29462931

Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective Study.

PubMed

Côrtes, Marina Carvalho Souza; Rosario, Pedro Weslley; Oliveira, Luís Fernando Faria; Calsolari, Maria Regina

2018-02-01

Interference of antithyroglobulin antibodies (TgAb) with serum thyroglobulin (Tg) can occur even at detectable TgAb concentrations below the reference limit (borderline TgAb). Thus, borderline TgAb is considered as TgAb positivity in patients with thyroid cancer. This prospective study evaluated patients with papillary thyroid carcinoma with undetectable Tg and normal neck ultrasonography (US) after total thyroidectomy and ablation with 131 I, and compared tumor persistence/recurrence and long-term Tg and TgAb behavior in those with borderline versus undetectable TgAb. A total of 576 patients were evaluated, divided into two groups: group A with undetectable TgAb (n = 420), and group B with borderline TgAb (n = 156). Groups A and B were similar in terms of patient and tumor characteristics. The time of follow-up ranged from 24 to 120 months. During follow-up, 11 (2.6%) patients in group A and 5 (3.2%) in group B developed a recurrence (p = 0.77). In group A, recurrences occurred in 9/390 patients who continued to have undetectable TgAb and in 1/9 patients who progressed to borderline TgAb. In group B, recurrences were detected in 1/84 patients who progressed to have undetectable TgAb, in 1/45 who still had borderline TgAb, and in 3/12 who developed elevated TgAb. In the presence of Tg levels <0.2 ng/mL, recurrences were detected in 2/486 patients with undetectable TgAb, in 0/67 with borderline TgAb, and in 3/12 with elevated TgAb. The results of post-therapy whole-body scanning (RxWBS) of 216 patients with Tg ≤0.2 ng/mL and normal US at the time of ablation were also analyzed. In low-risk patients, none of the 40 patients with borderline TgAb and none of the 94 with undetectable TgAb exhibited ectopic uptake on RxWBS. In intermediate-risk patients, lymph node metastases were detected by RxWBS in 1/25 (4%) with borderline TgAb and in 2/57 (3.5%) with undetectable TgAb. The results suggest that among low- or intermediate-risk patients with undetectable Tg and normal US after thyroidectomy, those with borderline TgAb are at no greater risk of tumor persistence or recurrence than those with undetectable TgAb. When undetectable Tg levels persist, recurrence should be suspected in the case of a TgAb elevation above the reference limit.

[The diagnostic importance of the new marker KIM-1 in kidney damage].

PubMed

Marchewka, Zofia; Płonka, Joanna

2013-07-24

In recent years, the rapid development of scientific research led to the introduction of strategies based on new markers that allow for estimation of the latent disease period before the clinical symptoms of actual kidney failure are revealed. The experimental tests carried out on animals and cell lines derived from the proximal tubule have made possible the detection of genes that are induced early after hypoxia. The protein products of these genes can be considered as useful markers for the diagnosis of renal failure. The induction of gene KIM-1 (called Kidney Injury Molecule-1) results in the formation of protein that can be considered as a diagnostic marker. This work describes the data on the structure, biological function and importance of determining the concentrations of KIM-1 in the diagnosis of drug-induced toxicity and kidney damage.

National position statement for the management of latent tuberculosis infection.

PubMed

Stock, David

2017-09-01

The primary role of any tuberculosis (TB) control program is to ensure the prompt identification and effective treatment of active disease. The host immune system often succeeds in containing the initial (or primary) infection with Mycobacterium tuberculosis (Mtb), but may fail to eliminate the pathogen. The persistence of viable organisms explains the potential for the development of active disease years or even decades after infection. This is known as latent tuberculosis infection (LTBI) although, rather than a distinct entity, this probably represents part of a dynamic spectrum. Individuals with LTBI are asymptomatic and it is therefore clinically undetectable. The World Health Organization (WHO) estimates that one-third of the global population has been infected with Mtb, with highest prevalence of LTBI in countries/regions with the highest prevalence of active disease. In 2013, 88% of 1322 notifications in Australia were in the overseas-born population (incidence 19.5 per 100,000 v. 1.0 per 100,000), with this proportion rising over the course of the last decade. Combined with epidemiological evidence of low local transmission, this strongly implies that the vast majority resulted from reactivation of latent infection acquired prior to immigration. Contrasting trends in TB incidence in other developed countries probably reflect differences in policy regarding LTBI. The diagnosis and treatment of LTBI represents an important opportunity for intervention by jurisdictional TB control programs. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.

A robust nonparametric method for quantifying undetected extinctions.

PubMed

Chisholm, Ryan A; Giam, Xingli; Sadanandan, Keren R; Fung, Tak; Rheindt, Frank E

2016-06-01

How many species have gone extinct in modern times before being described by science? To answer this question, and thereby get a full assessment of humanity's impact on biodiversity, statistical methods that quantify undetected extinctions are required. Such methods have been developed recently, but they are limited by their reliance on parametric assumptions; specifically, they assume the pools of extant and undetected species decay exponentially, whereas real detection rates vary temporally with survey effort and real extinction rates vary with the waxing and waning of threatening processes. We devised a new, nonparametric method for estimating undetected extinctions. As inputs, the method requires only the first and last date at which each species in an ensemble was recorded. As outputs, the method provides estimates of the proportion of species that have gone extinct, detected, or undetected and, in the special case where the number of undetected extant species in the present day is assumed close to zero, of the absolute number of undetected extinct species. The main assumption of the method is that the per-species extinction rate is independent of whether a species has been detected or not. We applied the method to the resident native bird fauna of Singapore. Of 195 recorded species, 58 (29.7%) have gone extinct in the last 200 years. Our method projected that an additional 9.6 species (95% CI 3.4, 19.8) have gone extinct without first being recorded, implying a true extinction rate of 33.0% (95% CI 31.0%, 36.2%). We provide R code for implementing our method. Because our method does not depend on strong assumptions, we expect it to be broadly useful for quantifying undetected extinctions. © 2016 Society for Conservation Biology.

Indication of prenatal diagnosis in pregnancies complicated by undetectable second-trimester maternal serum estriol levels.

PubMed

Minsart, Anne-Frédérique; Van Onderbergen, Anne; Jacques, Francotte; Kurt, Crener; Gillerot, Yves

2008-07-01

Undetectable maternal serum unconjugated estriol levels in the second-trimester screening test have been associated with congenital pathology and an adverse pregnancy outcome. We reviewed outcomes of pregnancies with undetectable levels of estriol (<0.25 ng/ml) in the triple-marker screening test and assessed the clinical value of this finding. We studied estriol values in 6,018 pregnant patients who underwent a triple-marker screening test during a seven-year period. 26 women had estriol levels at or below the sensitivity of the assay. The most common explanations were dating errors, prematurity, growth restriction and X-linked ichthyosis. We also observed one fetal death at 16 weeks, one severe threatened fetal abortion, one case of multiple congenital anomalies and one case of isolated adrenocorticotropin hormone deficiency. There were 6 women remaining with unexplained undetectable estriol. Undetectable maternal estriol values may indicate a severe fetal pathology and should lead to further investigations.

Quantitative analysis of CMV DNA in children the first year after liver transplantation.

PubMed

Kullberg-Lindh, Carola; Ascher, Henry; Krantz, Marie; Lindh, Magnus

2003-08-01

CMV infection is a major problem after solid organ transplantation especially in children where primary infection is more common than in adults. Early diagnosis is critical and might be facilitated by quantitative analysis of CMV DNA in blood. In this retrospective study of 18 children who had a liver transplantation 1995-2000, serum samples were analysed by Cobas Amplicor Monitor (Roche). Four patients developed symptomatic CMV infection at a mean time of 4 wk after transplantation. They showed maximum CMV DNA levels in serum of 26 400, 1900, 1300 and 970 copies/mL, respectively. In comparison, CA Monitor was positive, at a low level (415 copies/mL), in one of 11 patients with asymptomatic (4) or latent (7) infection. CMV IgM was detected at significant levels (> or =1/80) in all four patients with symptomatic, and in one with asymptomatic CMV infection. Eight patients were given one or several courses of ganciclovir. Five of these lacked symptoms of CMV disease, and had low (415 copies/mL) or undetectable CMV DNA in serum. The data suggest that quantitative analysis of CMV DNA may be of value in early identification of CMV disease and for avoiding unnecessary antiviral treatment.

Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo.

PubMed Central

Field, H J; Darby, G

1980-01-01

Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice. PMID:6247969

Long-term impact of highly active antiretroviral therapy on HIV-related health care costs.

PubMed

Keiser, P; Nassar, N; Kvanli, M B; Turner, D; Smith, J W; Skiest, D

2001-05-01

Highly active antiretroviral therapy (HAART) is associated with decreased opportunistic infections, hospitalization, and HIV-related health care costs over relatively short periods of time. We have previously demonstrated that decreases in total HIV cost are proportional to penetration of protease inhibitor therapy in our clinic. To determine the effects of HAART on HIV health care use and costs over 44 months. A comprehensive HIV service within a Veterans Affairs Medical Center. A cost-effectiveness analysis of HAART. The mean monthly number of hospital days, infectious diseases clinic visits, emergency room visits, non-HIV-related outpatient visits, inpatient costs, and antiretroviral treatment costs per patient were determined by dividing these during the period from January 1995 through June 1998 into four intervals. Viral load tests were available from October 1996. Cost-effectiveness of HAART was evaluated by determining the costs of achieving an undetectable viral load over time. Mean monthly hospitalization and associated inpatient costs decreased and remained low 2 years after the introduction of protease inhibitors (37 hospital days per 100 patients). Total cost decreased from $1905 per patient per month during the first quarter to $1090 per patient per month in the third quarter but increased to $1391 per patient per month in the fourth quarter. Antiretroviral treatment costs increased throughout the entire observation period from $79 per patient per month to $518 per patient per month. Hospitalization costs decreased from $1275 per patient per month in the first quarter to less than $500 per patient per month in each of the third and fourth quarters. The percentage of patients with a viral load <500 copies/mL increased from 21% in October 1996 to 47% in June of 1997 (p =.014). The cost of achieving an undetectable viral load decreased from $4438 per patient per month to $2669 per patient per month, but this trend did not reach statistical significance (p =.18). After an initial decrease, there was an increase in the total monthly cost of caring for HIV patients. Cost increases were primarily due to antiretroviral treatment costs, but these costs were offset by a marked decrease in inpatient-related costs. Increases in costs were not related to antiretroviral treatment failures as measured by the proportion of patients with low or undetectable viral loads. The cost of achieving an undetectable viral load remained stable despite increases in the cost of procuring antiretroviral agents.

Which type of breast cancers is undetectable on ring-type dedicated breast PET?

PubMed

Sasada, Shinsuke; Masumoto, Norio; Goda, Noriko; Kajitani, Keiko; Emi, Akiko; Kadoya, Takayuki; Okada, Morihito

2018-05-22

To assess the factors causing tumor undetectability on ring-type dedicated breast positron emission tomography (DbPET). A total of 265 patients (288 tumors) underwent DbPET and contrast-enhanced magnetic resonance imaging (MRI) in a prone position. The distance between the shallowest part of the breast tumor and the front end of the pectoralis major muscle on MRI was considered as the tumor-to-chest wall distance. Twenty-four tumors (8.3%) were not visualized via DbPET. The tumor-to-chest wall distance for undetectable tumors was shorter than that of the detectable tumors (23.0 mm vs 38.5 mm, P < 0.001). Multivariate analysis indicated that proximity to the chest wall and low-grade tumors were independent predicting factors for undetectable cancers. Among the 24 undetectable cancers, 15 tumors were proximal to the chest wall, suggesting that they were outside or at the edge of field of view (FOV), and 7 were low-grade tumors, suggesting insignificant 18 F-fluorodeoxyglucose (FDG) uptake. The factors of undetectable breast cancers on DbPET are classified into two types; outside or at the edge of FOV and insignificant FDG uptake. Copyright © 2018 Elsevier Inc. All rights reserved.

Paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of prostate-specific antigen during acute myocardial infarction.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-02-04

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Paroxysmal atrial fibrillation is a frequent complication of acute myocardial infarction. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including an increase in atrial fibrillation rate. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Moreover chronic renal failure presents an increased arrhythmic risk. Apparently spurious result has been reported in a work about mean serum prostate-specific antigen (PSA) concentration during acute myocardial infarction with mean serum PSA concentration significantly lower on day 2 than either day 1 or day 3 and it has been reported that these preliminary results could reflect several factors, such as antiinfarctual treatment, reduced physical activity or an acute-phase response. We present a case of paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of serum PSA concentration in a 90-year-old Italian man during acute myocardial infarction. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism and of chronic renal failure. Moreover, our report also confirms previous findings and extends the evaluation of PSA during acute myocardial infarction. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Damage Characterization Method for Structural Health Management Using Reduced Number of Sensor Inputs

NASA Technical Reports Server (NTRS)

Krishnamurthy, T.; Hochhalter, Jacob D.; Gallegos, Adam M.

2012-01-01

The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage (cracks) due to fatigue and low velocity foreign impacts that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage in critical structural components is highly important in developing efficient structural health management systems.

Damage Characterization Using the Extended Finite Element Method for Structural Health Management

NASA Technical Reports Server (NTRS)

Krishnamurthy, Thiagarajan; Gallegos, Adam M.

2011-01-01

The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign impact that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage/cracks in critical structural components is highly important in developing efficient structural health management systems.

NASA-DoD Lower Process Temperature Lead-Free Solder Project Overview

NASA Technical Reports Server (NTRS)

Kessel, Kurt R.

2014-01-01

This project is a follow-on effort to the Joint Council on Aging AircraftJoint Group on Pollution Prevention (JCAAJG-PP) Pb-free Solder Project and NASA-DoD Lead-Free Electronics Project which were the first projects to test the reliability of Pb-free solder joints against the requirements of the aerospace and military community. This effort would continue to build on the results from the JCAAJG-PP Lead-Free Solder Project and NASA-DoD Lead-Free Electronics Project while focusing on a particular failure mechanism currently plaguing Pb-free assemblies, pad cratering.The NASA-DoD Lead-Free Electronics Project confirmed that pad cratering is one of the dominant failure modes that occur in various board level reliability tests, especially under dynamic loading. Pad Cratering is a latent defect that may occur during assembly, rework, and post assembly handling and testing.

Genetic and Environmental Associations Between Procrastination and Internalizing/Externalizing Psychopathology.

PubMed

Gustavson, Daniel E; du Pont, Alta; Hatoum, Alexander S; Hyun Rhee, Soo; Kremen, William S; Hewitt, John K; Friedman, Naomi P

2017-09-01

Recent work on procrastination has begun to unravel the genetic and environmental correlates of this problematic behavior. However, little is known about how strongly procrastination is associated with internalizing and externalizing psychopathology, and the extent to which shared genetic/environmental factors or relevant personality constructs (e.g., fear of failure, impulsivity, and neuroticism) can inform the structure of these associations. The current study examined data from 764 young adult twins who completed questionnaires assessing procrastination and personality and structured interviews regarding psychopathology symptoms. Results indicated that procrastination was positively correlated with both internalizing and externalizing latent variables, and that these correlations were driven by shared genetic influences. Moreover, the association between procrastination and internalizing was accounted for by fear of failure and neuroticism, whereas the association between procrastination and externalizing was primarily explained by impulsivity. The role of procrastination in psychopathology is discussed using a framework that highlights common and broadband-specific variance.

Long-acting antiviral agents for HIV treatment

PubMed Central

Margolis, David A.; Boffito, Marta

2015-01-01

Purpose of review Long-acting antiretroviral (ARV) agents are currently under development for the treatment of chronic HIV infection. This review focuses on data recently produced on injectable ARVs for patients living with HIV/AIDS and on the patients’ perspectives on the use of these agents. Recent findings Crystalline nanoparticle formulations of the nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) and of the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) have progressed into phase II clinical trials as injectable maintenance therapy for patients living with HIV/AIDS with an undetectable viral load. Summary Phase II studies evaluating the coadministration of rilpivirine and cabotegravir intramuscularly to HIV-infected individuals with an undetectable viral load are currently underway. Rilpivirine and cabotegravir are characterized by different mechanisms of action against HIV and a favorable drug interaction profile, providing a rationale for coadministration. The high potency and low daily dosing requirements of oral cabotegravir and rilpivirine facilitate long-acting formulation development. Intramuscular dosing is preceded by an oral lead-in phase to assess safety and tolerability in individual participants. In addition to assessing the safety of injectable therapies in ongoing studies, it will be important to evaluate whether differences in drug adherence between injectable and oral therapies lead to different virologic outcomes, including rates of virologic failure and the emergence of resistance. Long-acting formulations may be associated with challenges, such as the management of adverse effects with persistent drug concentrations and the risk of virologic resistance, as drug concentrations decline following discontinuation. PMID:26049949

Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013).

PubMed

2013-11-01

In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is <500cells/μL; if the CD4(+) lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Complications of congenital portosystemic shunts in children: therapeutic options and outcomes.

PubMed

Franchi-Abella, Stéphanie; Branchereau, Sophie; Lambert, Virginie; Fabre, Monique; Steimberg, Clarisa; Losay, Jean; Riou, Jean-Yves; Pariente, Danièle; Gauthier, Frédéric; Jacquemin, Emmanuel; Bernard, Olivier

2010-09-01

Congenital portosystemic shunts are rare vascular malformations that lead to severe complications. Their management is controversial. The aim of this study was to propose a clear definition of the risks and management of congenital portosystemic shunts in children according to our experience and a review of the literature. Twenty-two children with a complicated congenital portosystemic shunt were studied in our institution. When necessary, management included portal pressure measurement and portal vein angiography during an occlusion test and closure of the shunt by surgical and/or endovascular methods. Five neonates with intrahepatic shunts presented with cholestasis that resolved spontaneously, and 17 older children presented with liver tumors (13) and/or hepatopulmonary syndrome (2), pulmonary artery hypertension (3), portosystemic encephalopathy (3), heart failure (1), and glomerulonephritis (1). The portosystemic shunt was extrahepatic (11) or intrahepatic (6). Portosystemic shunts were closed by endovascular methods in 5 children and surgically in 10, 4 of whom had portal pressure during occlusion above 35 mmHg and extremely hypoplastic or undetectable portal veins requiring banding of the fistula before closure. Shunt closure resulted in restoration of intrahepatic portal flow in all, with complete or partial regression of benign liver masses, and regression or stabilization of pulmonary, cardiac, neurological, and renal complications. Congenital portosystemic shunt carries risks of severe complications in children. Closure of a shunt persisting after age 2 years should be considered preventively. Intrahepatic portal flux restoration can be expected, even when intrahepatic portal veins are extremely hypoplastic or undetectable.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding

PubMed Central

Silver, Andrew; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert

2017-01-01

Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression. PMID:28751935

[Monotherapy in treatment-naïve patients].

PubMed

Arranz Caso, José Alberto

2008-12-01

The development of antiretroviral therapy (ART) with current triple drug combinations has dramatically reduced morbidity and mortality in HIV-infected patients. However, there is a need for less toxic treatments without sacrificing efficacy, as well as for less expensive drugs to facilitate universal access to this therapy. The protease inhibitors (PI) administered with ritonavir have a favorable pharmacokinetic profile and high genetic barrier and consequently are ideal candidates for use in monotherapy, thus avoiding the toxicity and cost associated with nucleoside analogs, as well as preserving drugs for future options. The promising results of studies performed with lopinavir/ritonavir (LPV/r) in induction-maintenance regimens in patients without prior failure to PIs encourage research into the cost-effectiveness of LPV/r in monotherapy from the beginning of ART. The few studies performed in this context seem to indicate the following: a) LPV/r monotherapy achieves undetectable viral loads in a large proportion of treatment-naïve patients, b) future treatment options are not compromised in patients not achieving undetectable viral loads since the likelihood of resistance mutations is low and treatment intensification achieves suppression of viral replication, and c) strategies for early detection can probably be considered in patients who will not achieve complete suppression with LPV/r monotherapy. Nevertheless, before LPV/r monotherapy can be considered a first-line option, new studies with larger samples and longer follow-up are required. These studies should pay particular attention to viral replication in areas where PI show less penetration.

Falsely undetectable TSH in a cohort of South Asian euthyroid patients.

PubMed

Drees, Julia C; Stone, Judith A; Reamer, C Randy; Arboleda, Victoria E; Huang, Karl; Hrynkow, Jane; Greene, Dina N; Petrie, Matthew S; Hoke, Carolyn; Lorey, Thomas S; Dlott, Richard S

2014-04-01

An index case of a clinically euthyroid woman of South Asian descent was identified with discordant TSH results: undetectable TSH on our routine assay and normal TSH on an alternate assay. Low TSH concentrations due to functionally compromising TSH mutations have been reported. Here we describe a new phenomenon of functional TSH that is undetectable by 4 widely used US Food and Drug Administration (FDA)-approved TSH immunoassays marketed by a single vendor. The purpose of this study was to identify additional cases and investigate the cause of the falsely undetectable TSH. All samples with TSH results of <0.01 μIU/mL were retested with a second TSH assay. Discordant samples were evaluated on up to 8 FDA-approved TSH immunoassays and the TSHβ gene was sequenced. Retrospectively, thyroid function tests, diagnoses, and medications from 1.6 million individuals were analyzed. Out of approximately 2 million individuals, we have identified a cohort of 20 hypothyroid and euthyroid patients of shared ethnicity with falsely undetectable TSH (<0.01 μIU/mL) in 4 of 8 commercially available TSH assays. Half of these individuals were initially treated based on repeated falsely undetectable TSH values (7 euthyroid patients were treated with methimazole and 2 hypothyroid patients had doses of levothyroxine decreased). In all cases, a retrospective chart review revealed that clinical assessments and free T4 and total T3 results were inconsistent with the undetectable TSH results. Specific antibodies failing to detect TSH in these cases were identified in the 4 affected assays. A novel TSHβ point mutation was identified. Our data suggest that these individuals have a previously unrecognized, functionally normal, TSH variant to which some monoclonal antibodies fail to bind. To assure appropriate patient management, clinicians and laboratorians need to be aware that certain TSH variants may be undetectable in some hyperselective TSH assays.

Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure.

PubMed

Calcagno, A; Pagani, N; Ariaudo, A; Arduino, G; Carcieri, C; D'Avolio, A; Marinaro, L; Tettoni, M C; Trentini, L; Di Perri, G; Bonora, S

2017-06-01

Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure. A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards. The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P  <   0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P  =   0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P  <   0.001), genotypic susceptibility score ≤2 ( P  =   0.001), lower nadir CD4 cell count ( P  =   0.003) and not being in the adherent group ( P  =   0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks. The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genomic Prostate Cancer Classifier Predicts Biochemical Failure and Metastases in Patients After Postoperative Radiation Therapy

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

Den, Robert B., E-mail: Robert.Den@jeffersonhospital.org; Feng, Felix Y.; Showalter, Timothy N.

2014-08-01

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.more » Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.« less

Updated hazard rate equations for dual safeguard systems.

PubMed

Rothschild, Marc

2007-04-11

A previous paper by this author [M.J. Rothschild, Updated hazard rate equation for single safeguards, J. Hazard. Mater. 130 (1-2) (2006) 15-20] showed that commonly used analytical methods for quantifying failure rates overestimates the risk in some circumstances. This can lead the analyst to mistakenly believe that a given operation presents an unacceptable risk. For a single safeguard system, a formula was presented in that paper that accurately evaluates the risk over a wide range of conditions. This paper expands on that analysis by evaluating the failure rate for dual safeguard systems. The safeguards can be activated at the same time or at staggered times, and the safeguard may provide an indication whether it was successful upon a challenge, or its status may go undetected. These combinations were evaluated using a Monte Carlo simulation. Empirical formulas for evaluating the hazard rate were developed from this analysis. It is shown that having the safeguards activate at the same time while providing positive feedback of their individual actions is the most effective arrangement in reducing the hazard rate. The hazard rate can also be reduced by staggering the testing schedules of the safeguards.

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

PubMed

Bruno, S; Bollani, S; Zignego, A L; Pascasio, J M; Magni, C; Ciancio, A; Caremani, M; Mangia, A; Marenco, S; Piovesan, S; Chemello, L; Babudieri, S; Moretti, A; Gea, F; Colletta, C; Perez-Alvarez, R; Forns, X; Larrubia, J R; Arenas, J; Crespo, J; Calvaruso, V; Ceccherini Silberstein, F; Maisonneuve, P; Craxì, A; Calleja, J L

2015-05-01

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/μL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile. © 2014 John Wiley & Sons Ltd.

Undetected penetrating bladder injuries presenting as a spontaneously expulsed bullet during voiding: a rare entity and review of the literature.

PubMed

Kuy, SreyRam; Somberg, Lewis B; Paul, Jasmeet; Brown, Nathaniel; Saving, Allegra; Codner, Panna A

2013-09-01

Patients presenting with a penetrating missile lodged in the pelvis are at risk for having a urinary tract injury. Once in the bladder, the missile can become impacted in the urethra, causing retention that requires extraction. Rarely, the missile can be expulsed spontaneously through the urethra. To describe the world literature regarding undetected penetrating bladder injuries presenting as spontaneously voided bullets and to contribute an additional case to the literature. We present a case report of a 37-year-old man who sustained a gunshot wound to the right buttock, with an undetected urinary system injury and subsequent spontaneous voiding of a bullet. There have been <10 cases reported in the literature of spontaneously expulsed bullets from the urethra, all of which were undetected injuries on initial presentation. Physicians should be aware of the potential for undetected urinary tract injuries in patients with penetrating missiles to the pelvis and understand the appropriate evaluation and management strategies for these injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

Pseudovitamin D deficiency rickets—a report from the Indian subcontinent

PubMed Central

Zargar, A. H.; Mithal, A.; Wani, A. I.; Laway, B. A.; Masoodi, S. R.; Bashir, M. I.; Ganie, M. A.

2000-01-01

Pseudovitamin D deficiency rickets (also called vitamin D dependent rickets type I) is one of the types of inherited rickets and is caused by a deficit in renal 25-hydroxyvitamin D 1α-hydroxylase. This form of rickets has not been reported from the Indian subcontinent. Three patients with this disorder are presented. These patients were all females aged 3-20 years and presented with growth failure and skeletal deformities. All had florid clinical and radiological rickets. The biochemical abnormalities seen included hypocalcaemia, hypophosphataemia, and hyperphosphatasia. All patients had grossly raised 25-hydroxyvitamin D concentrations and markedly low to undetectable concentrations of 1,25-dihydroxyvitamin D. A disturbing feature of this study was the late referral of the patients.


Keywords: 1α-hydroxylase; calcitriol; inherited rickets; vitamin D dependent rickets PMID:10824056

Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia.

PubMed Central

Lennard, L; Gibson, B E; Nicole, T; Lilleyman, J S

1993-01-01

Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standard protocol dose. Both were found to have undetectable intracellular activity of thiopurine methyltransferase (TPMT), an enzyme controlling one of the major alternative catabolic pathways of 6-mercaptopurine, and both produced higher concentrations of cytotoxic drug metabolites at 10-25% of the protocol dose than other patients taking 100%. It is supposed that these patients represent the 0.33% of the normal population constitutionally lacking TPMT. It is important to recognise such individuals both to avoid fatal bone marrow failure through inadvertent overdosage, and to be reassured that an adequate drug effect can be achieved at around 10% of the standard dose. PMID:8257179

Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.

PubMed

Eisenbach, Christoph; Longerich, Thomas; Fickenscher, Helmut; Schalasta, Gunnar; Stremmel, Wolfgang; Encke, Jens

2006-01-01

We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.

Failure Simulation Testing of the Z-1 Spacesuit Titanium Bearing Assemblies

NASA Technical Reports Server (NTRS)

de Baca, Richard C.; Juarez, Alfredo; Peralta, Stephen; Tylka, Jonathan; Rhodes, Richard

2016-01-01

The Z-2 is a candidate for NASA's next generation spacesuit, designed for a range of possible missions with enhanced mobility for spacewalks both on planetary surfaces and in microgravity. Increased mobility was accomplished through innovations in shoulder and hip joints, using a number of new bearings to allow spacesuit wearers to dip, walk, and bend with ease; all important tasks for a planetary explorer collecting samples or traveling over rough terrain. The Advanced Spacesuit Development Team of NASA Johnson Space Center requested that the NASA White Sands Test Facility (WSTF) perform a series failure simulation tests on three titanium bearing assemblies, an elemental part of the joint construction used in new spacesuit designs. This testing simulated two undetected failures within the bearings and as a result the objective of this test program was to evaluate whether a failed or failing bearing could result in ignition of the titanium race material due to friction. The first failure was an inner seal leak sufficient to pressurize the race with +99 percent oxygen. The second failure was an improperly installed or mismatched ball port that created a protrusion in the ball bearing race, partially obstructing the nominal rolling path of each ball bearing. When the spacesuit bearings are assembled, bearing balls are loaded into the assembly via a ball port. The ball port is specific and unique to each bearing assembly (matched pair). The simulated mismatched ball port is a significant source of friction, which would be caused by an assembly error. To evaluate this risk, the bearings were cycled in a simulated worst-case scenario environment, with operational loads, and potential flaw conditions. During test the amount of actuation torque required and heat generated through continuous operation were measured and the bearings were observed for sparks or burning events. This paper provides detailed descriptions of the test hardware, methodology, and results.

Flow-accelerated corrosion in power plants. Revision 1

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

Chexal, B.; Horowitz, J.; Dooley, B.

1998-07-01

Flow-Accelerated Corrosion (FAC) is a phenomenon that results in metal loss from piping, vessels, and equipment made of carbon steel. FAC occurs only under certain conditions of flow, chemistry, geometry, and material. Unfortunately, those conditions are common in much of the high-energy piping in nuclear and fossil-fueled power plants. Undetected, FAC will cause leaks and ruptures. Consequently, FAC has become a major issue, particularly for nuclear plants. Although major failures are rare, the consequences can be severe. In 1986, four men in the area of an FAC-induced pipe rupture were killed. Fossil plants too, are subject to FAC. In 1995,more » a failure at a fossil-fired plant caused two fatalities. In addition to concerns about personnel safety, FAC failures can pose challenges to plant safety. Regulatory agencies have therefore required nuclear utilities to institute formal programs to address FAC. Finally, a major FAC failure (like the one that happened in 1997 at a US nuclear power plant) can force a plant to shutdown and purchase replacement power at a price approaching a million dollars per day depending upon the MWe rating of the plant. A great deal of time and money has been spent to develop the technology to predict, detect, and mitigate FAC in order to prevent catastrophic failures. Over time, substantial progress has been made towards understanding and preventing FAC. The results of these efforts include dozens of papers, reports, calculations, and manuals, as well as computer programs and other tools. This book is written to provide a detailed treatment of the entire subject in a single document. Any complex issue requires balancing know-how, the risk of decision making, and a pragmatic engineering solution. This book addresses these by carrying out the necessary R and D and engineering along with plant knowledge to cover all quadrants of Chexal`s four quadrant known-unknown diagram, as seen in Figure i.« less

How we determined the most reliable solid medium for studying treatment of tuberculosis

PubMed Central

Heilig, Charles M.; Feng, Pei-Jean I.; Joloba, Moses L.; Johnson, John L.; Morgan, Karen; Gitta, Phineas; Boom, W. Henry; Mayanja-Kizza, Harriet; Eisenach, Kathleen D.; Bozeman, Lorna; Goldberg, Stefan V.

2014-01-01

Phase 2 clinical trials for tuberculosis (TB) treatment require reliable culture methods to determine presence or absence of Mycobacterium tuberculosis (Mtb) over the course of therapy, as these trials are based primarily on bacteriological endpoints. We evaluate which of 5 solid media is most reliable: Lowenstein-Jensen (LJ) egg-based medium and 4 Middlebrook agar media (nonselective 7H10 and 7H11 and selective 7H10 and 7H11). We analyze 393 specimens from 50 HIV-negative Ugandan adults with newly-diagnosed, pulmonary TB and high acid-fast bacillus smear grade. Specimens were collected every 2–4 weeks during the first 12 weeks of therapy. We compare the results for each culture to 2 composite reference standards—one that was deemed positive if any solid culture was positive for Mtb and another based on latent class analysis. Both reference standards established that the 2 selective Middlebrook media most reliably determine the presence or absence of Mtb (P<0.003), largely because of their lower contamination rates. We also showed that results on Middlebrook media were similar to each other, while LJ was most frequently discordant. Contaminated results appeared more likely to be truly negative than to harbor undetected Mtb. PMID:24661816

How we determined the most reliable solid medium for studying treatment of tuberculosis.

PubMed

Heilig, Charles M; Feng, Pei-Jean I; Joloba, Moses L; Johnson, John L; Morgan, Karen; Gitta, Phineas; Boom, W Henry; Mayanja-Kizza, Harriet; Eisenach, Kathleen D; Bozeman, Lorna; Goldberg, Stefan V

2014-05-01

Phase 2 clinical trials for tuberculosis (TB) treatment require reliable culture methods to determine presence or absence of Mycobacterium tuberculosis (Mtb) over the course of therapy, as these trials are based primarily on bacteriological endpoints. We evaluate which of 5 solid media is most reliable: Lowenstein-Jensen (LJ) egg-base medium and 4 Middlebrook agar media (nonselective 7H10 and 7H11 and selective 7H10 and 7H11). We analyze 393 specimens from 50 HIV-negative Ugandan adults with newly-diagnosed, pulmonary TB and high acid-fast bacillus smear grade. Specimens were collected every 2-4 weeks during the first 12 weeks of therapy. We compare the results for each culture to 2 composite reference standards--one that was deemed positive if any solid culture was positive for Mtb and another based on latent-class analysis. Both reference standards established that the 2 selective Middlebrook media most reliably determine the presence or absence of Mtb (P < 0.003), largely because of their lower contamination rates. We also showed that results on Middlebrook media were similar to each other, while LJ was most frequently discordant. Contaminated results appeared more likely to be truly negative than to harbor undetected Mtb. Published by Elsevier Ltd.

Role of Modulator of Inflammation Cyclooxygenase-2 in Gammaherpesvirus Mediated Tumorigenesis

PubMed Central

Gandhi, Jaya; Khera, Lohit; Gaur, Nivedita; Paul, Catherine; Kaul, Rajeev

2017-01-01

Chronic inflammation is recognized as a threat factor for cancer progression. Release of inflammatory molecules generates microenvironment which is highly favorable for development of tumor, cancer progression and metastasis. In cases of latent viral infections, generation of such a microenvironment is one of the major predisposing factors related to virus mediated tumorigenesis. Among various inflammatory mediators implicated in pathological process associated with cancer, the cyclooxygenase (COX) and its downstream effector molecules are of greater significance. Though the role of infectious agents in causing inflammation leading to transformation of cells has been more or less well established, however, the mechanism by which inflammation in itself modulates the events in life cycle of infectious agent is not very much clear. This is specifically important for gammaherpesviruses infections where viral life cycle is characterized by prolonged periods of latency when the virus remains hidden, immunologically undetectable and expresses only a very limited set of genes. Therefore, it is important to understand the mechanisms for role of inflammation in virus life cycle and tumorigenesis. This review is an attempt to summarize the latest findings highlighting the significance of COX-2 and its downstream signaling effectors role in life cycle events of gammaherpesviruses leading to progression of cancer. PMID:28400769

Networks and tuberculosis: an undetected community outbreak involving public places.

PubMed

Klovdahl, A S; Graviss, E A; Yaganehdoost, A; Ross, M W; Wanger, A; Adams, G J; Musser, J M

2001-03-01

After decades of decline in developed countries, there was a resurgence of tuberculosis in the mid-1980s accompanied by increased recognition that this infectious disease has long remained a major public health problem at the global level. New methods from molecular biology, in particular DNA 'fingerprinting' (of Mycobacterium tuberculosis), made it clear that current transmission and recent infection (in contrast to reactivation of earlier, latent infection) were much more significant than previously believed. Studies of tuberculosis outbreaks using these new tools pointed to complex networks through which infection was spreading and highlighted the need for new approaches to outbreak investigation and disease control. In the study reported here a new approach--combining methods from molecular biology, epidemiology and network analysis--was used to examine an outbreak of tuberculosis in Houston, Texas. Initial investigation using conventional strategies revealed few contacts among 37 patients with identical (six-band) DNA (IS6110-based) fingerprints but subsequent research uncovered over 40 places (including many gay bars) to which patients in this outbreak could be linked. Network methods were used to reconstruct an outbreak network and to quantify the relative importance (here, 'betweenness' centrality) of different actors (persons and places) playing a role in the outbreak. The multidisciplinary work provides the basis for a new approach to outbreak investigation and disease control.

Development of an in vivo model of Chlamydia abortus chronic infection in mice overexpressing IL-10.

PubMed

Del Río, Laura; Murcia, Antonio; Buendía, Antonio J; Álvarez, Daniel; Ortega, Nieves; Navarro, José A; Salinas, Jesús; Caro, María Rosa

2018-01-01

Chlamydia abortus, like other members of the family Chlamydiaceae, have a unique intracellular developmental cycle that is characterized by its chronic nature. Infection of a flock can remain undetected for months, until abortion occurs the following reproductive season but, to date, neither the location nor the mechanisms that maintain this latent phase are fully understood. Studies have shown that IL-10 produced as a response to certain micro-organisms sustains the intracellular survival of pathogens and increases host susceptibility to chlamydial infections. In order to induce a sustained infection C. abortus, transgenic mice that constitutively express IL-10 were infected and the immunological mechanisms that maintain infection in these mice were compared with the mechanisms of a resistant wild-type mouse strain. Viable bacteria could be detected in different tissues of transgenic mice up to 28 days after infection, as analysed by bacterial isolation and immunohistochemistry. Chronic infection in these mice was associated with an impaired recruitment of macrophages, decreased iNOS activity at the site of infection and a more diffuse distribution of inflammatory cells in the liver. This murine model can be of great help for understanding the immunological and bacterial mechanisms that lead to chronic chlamydial infections. Copyright © 2017 Elsevier B.V. All rights reserved.

How often is the office visit needed? Predicting total knee arthroplasty revision risk using pain/function scores.

PubMed

Hightower, Charles D; Hightower, Lisa S; Tatman, Penny J; Morgan, Patrick M; Gioe, Terence; Singh, Jasvinder A

2016-08-24

Most patients have favorable outcomes after primary total knee arthroplasty (TKA). Well-validated methods to predict the risk of poor outcomes have not been developed or implemented. Several patients have annual clinic visits despite well-funcitoning TKA, as a routine practice, to detect early failure requiring revision surgery. It is not known whether assessment of pain and function can be used as a predictive tool for early failure and revision to guide practice. Our objective was to determine whether pain and function can predict revision after TKA. We retrospectively studied data from a large prospectively gathered TKA registry to examine changes in outcome scores for primary TKAs undergoing revision compared to those not requiring revision to determine the factors that are predictive for revision. Of the 1,012 patients, 721 had had a single-sided primary TKA and had American Knee Society (AKS) Scores for three or more visits. 46 patients underwent revision, 23 acutely (fracture, traumatic component failure or acute infection) and 23 for latent causes (late implant loosening, progressive osteolysis, or pain and indolent infection). Mean age was 70 years for the non-revision patients, and 64 years for those revised. Both AKS Clinical and AKS Function Scores for non-revised patients were higher than in revision patients, higher in acute revision compared to latent revision patients. Significant predictors of revision surgery were preoperative, 3- and 15-month postoperative AKS Clinical Scores and 3-month AKS Function Scores. At 15-month post-TKA, a patient with a low calculated probability of revision, 32 % or less, was unlikely to require revision surgery with a negative predictive value of 99 %. Time dependent interval evaluation post-TKA with the AKS outcome scores may provide the ability to assign risk of revision to patients at the 15-month follow-up visit. If these findings can be replicated using a patient-reported measure, a virtual follow-up with patient-reported outcomes and X-ray review may be an alternative to clinic visit for patients doing well.

Does improvement in self-management skills predict improvement in quality of life and depressive symptoms? A prospective study in patients with heart failure up to one year after self-management education.

PubMed

Musekamp, Gunda; Schuler, Michael; Seekatz, Bettina; Bengel, Jürgen; Faller, Hermann; Meng, Karin

2017-02-15

Heart failure (HF) patient education aims to foster patients' self-management skills. These are assumed to bring about, in turn, improvements in distal outcomes such as quality of life. The purpose of this study was to test the hypothesis that change in self-reported self-management skills observed after participation in self-management education predicts changes in physical and mental quality of life and depressive symptoms up to one year thereafter. The sample comprised 342 patients with chronic heart failure, treated in inpatient rehabilitation clinics, who received a heart failure self-management education program. Latent change modelling was used to analyze relationships between both short-term (during inpatient rehabilitation) and intermediate-term (after six months) changes in self-reported self-management skills and both intermediate-term and long-term (after twelve months) changes in physical and mental quality of life and depressive symptoms. Short-term changes in self-reported self-management skills predicted intermediate-term changes in mental quality of life and long-term changes in physical quality of life. Intermediate-term changes in self-reported self-management skills predicted long-term changes in all outcomes. These findings support the assumption that improvements in self-management skills may foster improvements in distal outcomes.

Do Crashes and Near Crashes in Simulator-Based Training Enhance Novice Drivers’ Visual Search for Latent Hazards?

PubMed Central

Vlakveld, Willem; Romoser, Matthew R. E.; Mehranian, Hasmik; Diete, Frank; Pollatsek, Alexander; Fisher, Donald L.

2012-01-01

Young drivers (younger than 25 years of age) are overrepresented in crashes. Research suggests that a relevant cause is inadequate visual search for possible hazards that are hidden from view. The objective of this study was to develop and evaluate a low-cost, fixed-base simulator training program that would address this failure. It was hypothesized that elicited crashes in the simulator training would result in better scanning for latent hazards in scenarios that were similar to the training scenarios but situated in a different environment (near transfer), and, to a lesser degree, would result in better scanning in scenarios that had altogether different latent hazards than those contained in the training scenarios (far transfer). To test the hypotheses, 18 trained and 18 untrained young novice drivers were evaluated on an advanced driving simulator (different from the training simulator). The eye movements of both groups were measured. In near transfer scenarios, trained drivers fixated the hazardous region 84% of the time, compared with only 57% of untrained drivers. In far transfer scenarios, trained drivers fixated the hazardous region 71 % of the time, compared with only 53% of untrained drivers. The differences between trained and untrained drivers in both the near transfer scenarios and the far transfer scenarios were significant, with a large effect size in the near transfer scenarios and a medium effect size in the far transfer scenarios [respectively: U = 63.00, p(2-tailed) < .01, r = −.53, and U = 88.00, p(2-tailed)<.05,r = −.39]. PMID:23082041

Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

PubMed

Berenguer, Juan; Polo, Rosa; Aldeguer, José López; Lozano, Fernando; Aguirrebengoa, Koldo; Arribas, José Ramón; Blanco, José Ramón; Boix, Vicente; Casado, José Luis; Clotet, Bonaventura; Crespo, Manuel; Domingo, Pere; Estrada, Vicente; García, Federico; Gatell, José María; González-García, Juan; Gutiérrez, Félix; Iribarren, José Antonio; Knobel, Hernando; Llibre, Josep María; Locutura, Jaime; López, Juan Carlos; Miró, José M; Moreno, Santiago; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz-Moreno, José; Sanz, Jesús; Téllez, María Jesús; Tuset, Montserrat; Rivero, Antonio

2015-10-01

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Multimorbidity and survival for patients with acute myocardial infarction in England and Wales: Latent class analysis of a nationwide population-based cohort.

PubMed

Hall, Marlous; Dondo, Tatendashe B; Yan, Andrew T; Mamas, Mamas A; Timmis, Adam D; Deanfield, John E; Jernberg, Tomas; Hemingway, Harry; Fox, Keith A A; Gale, Chris P

2018-03-01

There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which multimorbidity is associated with long-term survival following AMI. This national observational study included 693,388 patients (median age 70.7 years, 452,896 [65.5%] male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 [95% CI 39.0-40.0], 38.2 [27.7-26.8], and 26.6 [25.2-26.4] deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; β-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3-2.5) and 1.5-fold (95% CI 1.4-1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population. Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes. ClinicalTrials.gov NCT03037255.

Score tests for independence in semiparametric competing risks models.

PubMed

Saïd, Mériem; Ghazzali, Nadia; Rivest, Louis-Paul

2009-12-01

A popular model for competing risks postulates the existence of a latent unobserved failure time for each risk. Assuming that these underlying failure times are independent is attractive since it allows standard statistical tools for right-censored lifetime data to be used in the analysis. This paper proposes simple independence score tests for the validity of this assumption when the individual risks are modeled using semiparametric proportional hazards regressions. It assumes that covariates are available, making the model identifiable. The score tests are derived for alternatives that specify that copulas are responsible for a possible dependency between the competing risks. The test statistics are constructed by adding to the partial likelihoods for the individual risks an explanatory variable for the dependency between the risks. A variance estimator is derived by writing the score function and the Fisher information matrix for the marginal models as stochastic integrals. Pitman efficiencies are used to compare test statistics. A simulation study and a numerical example illustrate the methodology proposed in this paper.

A Joint Model for Longitudinal Measurements and Survival Data in the Presence of Multiple Failure Types

PubMed Central

Elashoff, Robert M.; Li, Gang; Li, Ning

2009-01-01

Summary In this article we study a joint model for longitudinal measurements and competing risks survival data. Our joint model provides a flexible approach to handle possible nonignorable missing data in the longitudinal measurements due to dropout. It is also an extension of previous joint models with a single failure type, offering a possible way to model informatively censored events as a competing risk. Our model consists of a linear mixed effects submodel for the longitudinal outcome and a proportional cause-specific hazards frailty submodel (Prentice et al., 1978, Biometrics 34, 541-554) for the competing risks survival data, linked together by some latent random effects. We propose to obtain the maximum likelihood estimates of the parameters by an expectation maximization (EM) algorithm and estimate their standard errors using a profile likelihood method. The developed method works well in our simulation studies and is applied to a clinical trial for the scleroderma lung disease. PMID:18162112

Polygenic loading for major depression is associated with specific medical comorbidity

PubMed Central

McCoy, T H; Castro, V M; Snapper, L; Hart, K; Januzzi, J L; Huffman, J C; Perlis, R H

2017-01-01

Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation. Three topics showed experiment-wide association with the depression liability score; these included diagnostic groups representing greater prevalence of mood and anxiety disorders, greater prevalence of cardiac ischemia, and a decreased prevalence of heart failure. The latter two associations persisted even among individuals with no mood disorder diagnosis. This application of a novel method for grouping related diagnoses in biobanks indicate shared genetic risk for depression and cardiac disease, with a pattern suggesting greater ischemic risk and diminished heart failure risk. PMID:28926002

The problem of latent attentional capture: Easy visual search conceals capture by task-irrelevant abrupt onsets.

PubMed

Gaspelin, Nicholas; Ruthruff, Eric; Lien, Mei-Ching

2016-08-01

Researchers are sharply divided regarding whether irrelevant abrupt onsets capture spatial attention. Numerous studies report that they do and a roughly equal number report that they do not. This puzzle has inspired numerous attempts at reconciliation, none gaining general acceptance. The authors propose that abrupt onsets routinely capture attention, but the size of observed capture effects depends critically on how long attention dwells on distractor items which, in turn, depends critically on search difficulty. In a series of spatial cuing experiments, the authors show that irrelevant abrupt onsets produce robust capture effects when visual search is difficult, but not when search is easy. Critically, this effect occurs even when search difficulty varies randomly across trials, preventing any strategic adjustments of the attentional set that could modulate probability of capture by the onset cue. The authors argue that easy visual search provides an insensitive test for stimulus-driven capture by abrupt onsets: even though onsets truly capture attention, the effects of capture can be latent. This observation helps to explain previous failures to find capture by onsets, nearly all of which used an easy visual search. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Completing treatment for latent tuberculosis: patient background matters.

PubMed

Kan, B; Kalin, M; Bruchfeld, J

2013-05-01

Treatment of latent infection with Mycobacterium tuberculosis effectively reduces future activation and transmission of tuberculosis. However, patient adherence to preventive treatment influences its effectiveness. Treatment completion is commonly considered as a proxy for adherence. To identify factors associated with failure to complete preventive treatment. Data from 415 consecutive patients who started preventive treatment at the Karolinska University Hospital, Stockholm, Sweden, between 2002 and 2007 were collected and treatment completion was evaluated. Patients were classified as 'completers' or 'non-completers'. Association between treatment completion status and patient characteristics was assessed using logistic regression. Younger patients, patients originating from Somalia and asylum seekers were more likely to be non-completers. The proportion of completers increased from 71% in 2002 to 87% in 2007. However, this trend appears to be caused mostly by an increase in the proportion of European patients. The finding of a low rate of treatment completion among Somalis should be regarded as a call for intervention on the individual patient level, also taking into account socio-cultural aspects such as perceptions of health care by the Somali community. Treatment completion continues to be of concern as it is not improving among risk populations.

The Problem of Latent Attentional Capture: Easy Visual Search Conceals Capture by Task-Irrelevant Abrupt Onsets

PubMed Central

Gaspelin, Nicholas; Ruthruff, Eric; Lien, Mei-Ching

2016-01-01

Researchers are sharply divided regarding whether irrelevant abrupt onsets capture spatial attention. Numerous studies report that they do and a roughly equal number report that they do not. This puzzle has inspired numerous attempts at reconciliation, none gaining general acceptance. We propose that abrupt onsets routinely capture attention, but the size of observed capture effects depends critically on how long attention dwells on distractor items which, in turn, depends critically on search difficulty. In a series of spatial cuing experiments, we show that irrelevant abrupt onsets produce robust capture effects when visual search is difficult, but not when search is easy. Critically, this effect occurs even when search difficulty varies randomly across trials, preventing any strategic adjustments of the attentional set that could modulate probability of capture by the onset cue. We argue that easy visual search provides an insensitive test for stimulus-driven capture by abrupt onsets: even though onsets truly capture attention, the effects of capture can be latent. This observation helps to explain previous failures to find capture by onsets, nearly all of which employed an easy visual search. PMID:26854530

Failure modes and effects analysis (FMEA) for Gamma Knife radiosurgery.

PubMed

Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Flickinger, John; Arai, Yoshio; Vacsulka, Jonet; Feng, Wenzheng; Monaco, Edward; Niranjan, Ajay; Lunsford, L Dade; Huq, M Saiful

2017-11-01

Gamma Knife radiosurgery is a highly precise and accurate treatment technique for treating brain diseases with low risk of serious error that nevertheless could potentially be reduced. We applied the AAPM Task Group 100 recommended failure modes and effects analysis (FMEA) tool to develop a risk-based quality management program for Gamma Knife radiosurgery. A team consisting of medical physicists, radiation oncologists, neurosurgeons, radiation safety officers, nurses, operating room technologists, and schedulers at our institution and an external physicist expert on Gamma Knife was formed for the FMEA study. A process tree and a failure mode table were created for the Gamma Knife radiosurgery procedures using the Leksell Gamma Knife Perfexion and 4C units. Three scores for the probability of occurrence (O), the severity (S), and the probability of no detection for failure mode (D) were assigned to each failure mode by 8 professionals on a scale from 1 to 10. An overall risk priority number (RPN) for each failure mode was then calculated from the averaged O, S, and D scores. The coefficient of variation for each O, S, or D score was also calculated. The failure modes identified were prioritized in terms of both the RPN scores and the severity scores. The established process tree for Gamma Knife radiosurgery consists of 10 subprocesses and 53 steps, including a subprocess for frame placement and 11 steps that are directly related to the frame-based nature of the Gamma Knife radiosurgery. Out of the 86 failure modes identified, 40 Gamma Knife specific failure modes were caused by the potential for inappropriate use of the radiosurgery head frame, the imaging fiducial boxes, the Gamma Knife helmets and plugs, the skull definition tools as well as other features of the GammaPlan treatment planning system. The other 46 failure modes are associated with the registration, imaging, image transfer, contouring processes that are common for all external beam radiation therapy techniques. The failure modes with the highest hazard scores are related to imperfect frame adaptor attachment, bad fiducial box assembly, unsecured plugs/inserts, overlooked target areas, and undetected machine mechanical failure during the morning QA process. The implementation of the FMEA approach for Gamma Knife radiosurgery enabled deeper understanding of the overall process among all professionals involved in the care of the patient and helped identify potential weaknesses in the overall process. The results of the present study give us a basis for the development of a risk based quality management program for Gamma Knife radiosurgery. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Anger, hostility, and hospitalizations in patients with heart failure.

PubMed

Keith, Felicia; Krantz, David S; Chen, Rusan; Harris, Kristie M; Ware, Catherine M; Lee, Amy K; Bellini, Paula G; Gottlieb, Stephen S

2017-09-01

Heart failure patients have a high hospitalization rate, and anger and hostility are associated with coronary heart disease morbidity and mortality. Using structural equation modeling, this prospective study assessed the predictive validity of anger and hostility traits for cardiovascular and all-cause rehospitalizations in patients with heart failure. 146 heart failure patients were administered the STAXI and Cook-Medley Hostility Inventory to measure anger, hostility, and their component traits. Hospitalizations were recorded for up to 3 years following baseline. Causes of hospitalizations were categorized as heart failure, total cardiac, noncardiac, and all-cause (sum of cardiac and noncardiac). Measurement models were separately fit for Anger and Hostility, followed by a Confirmatory Factor Analysis to estimate the relationship between the Anger and Hostility constructs. An Anger model consisted of State Anger, Trait Anger, Anger Expression Out, and Anger Expression In, and a Hostility model included Cynicism, Hostile Affect, Aggressive Responding, and Hostile Attribution. The latent construct of Anger did not predict any of the hospitalization outcomes, but Hostility significantly predicted all-cause hospitalizations. Analyses of individual trait components of each of the 2 models indicated that Anger Expression Out predicted all-cause and noncardiac hospitalizations, and Trait Anger predicted noncardiac hospitalizations. None of the individual components of Hostility were related to rehospitalizations or death. The construct of Hostility and several components of Anger are predictive of hospitalizations that were not specific to cardiac causes. Mechanisms common to a variety of health problems, such as self-care and risky health behaviors, may be involved in these associations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Fatal outcome of an hydrogen sulfide poisoning].

PubMed

Querellou, E; Jaffrelot, M; Savary, D; Savry, C; Perfus, J-P

2005-10-01

We report a case of fatal outcome poisoning by massive exposure to hydrogen sulfide of a sewer worker. This rare event was associated with a moderate intoxication of two members of the rescue team. The death was due to asystole and massive lung oedema. Autopsy analysis showed diffuse necrotic lesions in lungs. Hydrogen sulfide is a direct and systemic poison, produced by organic matter decomposition. The direct toxicity mechanism is still unclear. The systemic toxicity is due to an acute toxicity by oxygen depletion at cellular level. It is highly diffusable and potentially very dangerous. At low concentration, rotten egg smell must trigger hydrogen sulfide suspicion since at higher concentration it is undetectable, making intoxication possible. In case of acute intoxication, there is an almost instantaneous cardiovascular failure and a rapid death. Hydrogen sulfide exposure requires prevention measures and more specifically the use of respiratory equipment for members of the rescue team.

Definition of mutually optimum NDI and proof test criteria for 2219 aluminum pressure vessels. Volume 1: Methods

NASA Technical Reports Server (NTRS)

Schwartzberg, F. R.; King, R. G.; Todd, P. H., Jr.

1979-01-01

The requirements for proof testing and nondestructive inspection of aluminum pressure vessels were discussed. The following conclusions are (1) lack-of-fusion weld defects are sufficiently tight in the as-welded condition to be considered undetectable; (2) proof-level loads are required to fully open lack-of-fusion weld defects; (3) significant crack opening occurs at subproof levels so that an inspection enhancement loading treatment designed to avoid catastrophic failure is feasible; (4) currently used proof levels for 2219 pressure vessels are adequate for postproof inspection; (5) quantification of defect size and location using collimated ultrasonic pitch-catch techniques appears sufficiently feasible for tankage to warrant developmental work; (6) for short-time single-cycle pressure-vessel applications, postproof inspection is desirable; and (7) for long-term multiple-cycle pressure-vessel applications, postproof inspection is essential for life assurance.

DESNT: A Poor Prognosis Category of Human Prostate Cancer.

PubMed

Luca, Bogdan-Alexandru; Brewer, Daniel S; Edwards, Dylan R; Edwards, Sandra; Whitaker, Hayley C; Merson, Sue; Dennis, Nening; Cooper, Rosalin A; Hazell, Steven; Warren, Anne Y; Eeles, Rosalind; Lynch, Andy G; Ross-Adams, Helen; Lamb, Alastair D; Neal, David E; Sethia, Krishna; Mills, Robert D; Ball, Richard Y; Curley, Helen; Clark, Jeremy; Moulton, Vincent; Cooper, Colin S

2017-03-06

A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. Biochemical failure was assessed using log-rank analysis and Cox regression analysis. Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p=2.65×10 -5 , p=4.28×10 -5 , and p=2.98×10 -8 ). When these three datasets were combined the independent predictive value of DESNT membership was p=1.61×10 -7 compared with p=1.00×10 -5 for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease. Prostate cancer, unlike breast cancer, does not have a robust classification framework. We propose that this failure has occurred because prostate cancer samples selected for analysis frequently have heterozygous compositions (individual samples are made up of many different parts that each have different characteristics). Applying a mathematical approach that can overcome this problem we identify a novel poor prognosis category of human prostate cancer called DESNT. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Data on the interexaminer variation of minutia markup on latent fingerprints.

PubMed

Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

2016-09-01

The data in this article supports the research paper entitled "Interexaminer variation of minutia markup on latent fingerprints" [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the "White Box Latent Print Examiner Study," in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent.

EGFR mutation status of paired cerebrospinal fluid and plasma samples in EGFR mutant non-small cell lung cancer with leptomeningeal metastases.

PubMed

Zhao, Jing; Ye, Xin; Xu, Yan; Chen, Minjiang; Zhong, Wei; Sun, Yun; Yang, Zhenfan; Zhu, Guanshan; Gu, Yi; Wang, Mengzhao

2016-12-01

Central nervous system (CNS) is the prevalent site for metastases in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-relapsed NSCLC patients. To understand the EGFR mutation status in paired cerebrospinal fluid (CSF) and plasma samples after EGFR-TKI treatment failure might be useful to guide the treatment of intra- and extracranial tumors in those patients. Paired CSF and plasma samples were collected from seven NSCLC patients with CNS metastases after EGFR-TKI failure. EGFR mutations were tested by amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) methods. Gefitinib concentrations were evaluated by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). EGFR mutations were detected in all seven CSF samples, including three of E19-Del, three of L858R and one of E19-Del&T790M by both methods. On the other hand, majority of the matched plasma samples (5/7) were negative for EGFR mutations by both methods. The other two plasma samples were positive for E19-Del&T790M by ddPCR, and one of them had undetectable T790M by ARMS. Gefitinib concentration in CSF was much lower than that in plasma (mean CSF/plasma ratio: 1.8 %). After EGFR-TKI failure, majority of the NSCLC patients with CNS metastases remained positive detection of EGFR sensitive mutations in CSF, but much less detection in the matched plasma. Significantly low exposure of gefitinib in CSF might explain the intracranial protection of the EGFR sensitive mutation positive tumor cells.

Psyche at the end of life: Psychiatric symptoms are prevalent in patients admitted to a palliative care unit.

PubMed

Masel, Eva K; Berghoff, Anna S; Mladen, Aleksandra; Schur, Sophie; Maehr, Bruno; Kirchhoff, Magdalena; Simanek, Ralph; Bauer, Martin; Watzke, Herbert H; Amering, Michaela

2016-06-01

Our aim was to evaluate the frequency and treatment of psychiatric symptoms in patients at palliative care units (PCUs). Patients admitted to one of five participating PCUs in Austria were included. The short version of the Patient Health Questionnaire (PHQ-D) was used to evaluate their mental health status. Pain intensity was rated on a numeric rating scale (NRS) from 0 to 10 by patients and physicians. Patients with a previously diagnosed psychiatric disorder were compared to those without or with newly diagnosed psychiatric symptoms, based on PHQ-D results. Pain and psychopharmacological medication were assessed. Opioid doses were converted into oral morphine equivalents (OMEs). Some 68 patients were included. Previously undetected psychiatric symptoms were identified in 38% (26 of 68), preexisting psychiatric comorbidities were evident in 25% (17), and no psychiatric symptoms were observed in 37% (25). Patients with a preexisting psychiatric comorbidity received antidepressants and benzodiazepines significantly more often than patients without or with previously undetected psychiatric symptoms (p < 0.001). Patient and physician median NRS ratings of pain intensity correlated significantly (p = 0.001). Median NRS rating showed no significant difference between patients with preexisting, previously undetected, or without psychiatric symptoms. OMEs did not differ significantly between preexisting, without, or previously undetected psychiatric symptoms. Patients with undetected and preexisting psychiatric comorbidities had a greater impairment in their activities of daily living than patients without psychiatric symptoms (p = 0.003). Undetected psychiatric comorbidities are common in patients receiving palliative care. Screening for psychiatric symptoms should be integrated into standard palliative care to optimize treatment and reduce the psychosocial burden of the disease.

Becoming "Undetectable": Longitudinal Narratives of Gay Men's Sex Lives After a Recent HIV Diagnosis.

PubMed

Grace, Daniel; Chown, Sarah A; Kwag, Michael; Steinberg, Malcolm; Lim, Elgin; Gilbert, Mark

2015-08-01

We explore gay men's sex life narratives following their diagnosis with an acute or recent HIV infection. All participants received an acute (n = 13) or recent (n = 12) HIV diagnosis and completed a series of self-administered questionnaires and in-depth qualitative interviews over a one-year period or longer. Over the course of four qualitative interviews, participants frequently spoke of the role of medications (e.g., decisions to start treatment) and changing viral loads (e.g., discourses of becoming "undetectable") in relation to their sex lives since being diagnosed with HIV. Many men talked about milestones relating to initiating medication and viral load as informing their shifting sexual behaviors and identities as HIV-positive--or "undetectable"--gay men. The narratives of our participants provide insight regarding complex negotiations and processes of decision-making over time related to sex, counseling needs, treatment initiation, viral load, and the significance of undetectability as an emergent identity.

Latent heat induced rotation limited aggregation in 2D ice nanocrystals.

PubMed

Bampoulis, Pantelis; Siekman, Martin H; Kooij, E Stefan; Lohse, Detlef; Zandvliet, Harold J W; Poelsema, Bene

2015-07-21

The basic science responsible for the fascinating shapes of ice crystals and snowflakes is still not understood. Insufficient knowledge of the interaction potentials and the lack of relevant experimental access to the growth process are to blame for this failure. Here, we study the growth of fractal nanostructures in a two-dimensional (2D) system, intercalated between mica and graphene. Based on our scanning tunneling spectroscopy data, we provide compelling evidence that these fractals are 2D ice. They grow while they are in material contact with the atmosphere at 20 °C and without significant thermal contact to the ambient. The growth is studied in situ, in real time and space at the nanoscale. We find that the growing 2D ice nanocrystals assume a fractal shape, which is conventionally attributed to Diffusion Limited Aggregation (DLA). However, DLA requires a low mass density mother phase, in contrast to the actual currently present high mass density mother phase. Latent heat effects and consequent transport of heat and molecules are found to be key ingredients for understanding the evolution of the snow (ice) flakes. We conclude that not the local availability of water molecules (DLA), but rather them having the locally required orientation is the key factor for incorporation into the 2D ice nanocrystal. In combination with the transport of latent heat, we attribute the evolution of fractal 2D ice nanocrystals to local temperature dependent rotation limited aggregation. The ice growth occurs under extreme supersaturation, i.e., the conditions closely resemble the natural ones for the growth of complex 2D snow (ice) flakes and we consider our findings crucial for solving the "perennial" snow (ice) flake enigma.

Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.

PubMed

Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L

2016-01-01

Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4-5 days earlier.

Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus

PubMed Central

Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L.

2017-01-01

Aim Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Materials and methods Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. Results In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4–5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. Conclusions The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4–5 days earlier. PMID:25859798

Stability of ARDS subphenotypes over time in two randomised controlled trials.

PubMed

Delucchi, Kevin; Famous, Katie R; Ware, Lorraine B; Parsons, Polly E; Thompson, B Taylor; Calfee, Carolyn S

2018-05-01

Two distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time. To determine the stability of ARDS subphenotypes over time. Secondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes. In ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment. ARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials. © 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.

Latent heat induced rotation limited aggregation in 2D ice nanocrystals

NASA Astrophysics Data System (ADS)

Bampoulis, Pantelis; Siekman, Martin H.; Kooij, E. Stefan; Lohse, Detlef; Zandvliet, Harold J. W.; Poelsema, Bene

2015-07-01

The basic science responsible for the fascinating shapes of ice crystals and snowflakes is still not understood. Insufficient knowledge of the interaction potentials and the lack of relevant experimental access to the growth process are to blame for this failure. Here, we study the growth of fractal nanostructures in a two-dimensional (2D) system, intercalated between mica and graphene. Based on our scanning tunneling spectroscopy data, we provide compelling evidence that these fractals are 2D ice. They grow while they are in material contact with the atmosphere at 20 °C and without significant thermal contact to the ambient. The growth is studied in situ, in real time and space at the nanoscale. We find that the growing 2D ice nanocrystals assume a fractal shape, which is conventionally attributed to Diffusion Limited Aggregation (DLA). However, DLA requires a low mass density mother phase, in contrast to the actual currently present high mass density mother phase. Latent heat effects and consequent transport of heat and molecules are found to be key ingredients for understanding the evolution of the snow (ice) flakes. We conclude that not the local availability of water molecules (DLA), but rather them having the locally required orientation is the key factor for incorporation into the 2D ice nanocrystal. In combination with the transport of latent heat, we attribute the evolution of fractal 2D ice nanocrystals to local temperature dependent rotation limited aggregation. The ice growth occurs under extreme supersaturation, i.e., the conditions closely resemble the natural ones for the growth of complex 2D snow (ice) flakes and we consider our findings crucial for solving the "perennial" snow (ice) flake enigma.

Routes to failure: analysis of 41 civil aviation accidents from the Republic of China using the human factors analysis and classification system.

PubMed

Li, Wen-Chin; Harris, Don; Yu, Chung-San

2008-03-01

The human factors analysis and classification system (HFACS) is based upon Reason's organizational model of human error. HFACS was developed as an analytical framework for the investigation of the role of human error in aviation accidents, however, there is little empirical work formally describing the relationship between the components in the model. This research analyses 41 civil aviation accidents occurring to aircraft registered in the Republic of China (ROC) between 1999 and 2006 using the HFACS framework. The results show statistically significant relationships between errors at the operational level and organizational inadequacies at both the immediately adjacent level (preconditions for unsafe acts) and higher levels in the organization (unsafe supervision and organizational influences). The pattern of the 'routes to failure' observed in the data from this analysis of civil aircraft accidents show great similarities to that observed in the analysis of military accidents. This research lends further support to Reason's model that suggests that active failures are promoted by latent conditions in the organization. Statistical relationships linking fallible decisions in upper management levels were found to directly affect supervisory practices, thereby creating the psychological preconditions for unsafe acts and hence indirectly impairing the performance of pilots, ultimately leading to accidents.

Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.

PubMed

Lee, Christopher S; Mudd, James O; Gelow, Jill M; Nguyen, Thuan; Hiatt, Shirin O; Green, Jennifer K; Denfeld, Quin E; Bidwell, Julie T; Grady, Kathleen L

2014-01-01

Unexplained heterogeneity in response to ventricular assist device (VAD) implantation for the management of advanced heart failure impedes our ability to predict favorable outcomes, provide adequate patient and family education, and personalize monitoring and symptom management strategies. The purpose of this article was to describe the background and the design of a study entitled "Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure" (PREMISE). PREMISE is a prospective cohort study designed to (1) identify common and distinct trajectories of change in physical and psychological symptom burden; (2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction; and (3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Latent growth mixture modeling, including parallel process and cross-classification modeling, will be used to address the study aims and will entail identifying trajectories, quantifying associations between trajectories and both clinical and quality-of-life outcomes, and identifying predictors of favorable symptom and biomarker responses to VAD implantation. Research findings from the PREMISE study will be used to enhance shared patient and provider decision making and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.

Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates.

PubMed

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2013-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. Systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS, and postinfective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern reflecting cellular injury. Circulating bacterial 16S DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed quantitative polymerase chain reaction assays to quantify these markers, and predicting their plasma levels might help distinguish sterile injury from infection. To study these events in primates, we assayed banked serum from Papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis delta Sterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to "severe" sepsis and death, we studied animals where anthrax was pretreated with drotrecogin alfa (activated protein C), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against nonlethal E. coli bacteremia and against sterile tissue injury from Shiga-like toxin 1. Bacterial DNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Shiga-like toxin 1 increased mtDNA, but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sublethal E. coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal anthrax challenge (n = 4), bDNA increased transiently, but mtDNA levels remained elevated until death, consistent with persistent septic tissue damage after bacterial clearance. Critically, activated protein C pretreatment (n = 4) allowed mtDNA levels to decay after bacterial clearance with sparing of organ function and survival. In summary, host tissue injury correlates with mtDNA whether infective or sterile. Mitochondrial DNA and bDNA polymerase chain reactions can quantify tissue injury incurred by septic or sterile mechanisms and suggest the source of SIRS of unknown origin.

Plasma Bacterial and Mitochondrial DNA Distinguish Bacterial Sepsis from Sterile SIRS and Quantify Inflammatory Tissue Injury in Nonhuman Primates

PubMed Central

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2012-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. SIRS can cause organ dysfunction and death but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS and post-infective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern (DAMP) reflecting cellular injury. Circulating bacterial 16S-DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed qPCR assays to quantify these markers and predicted their plasma levels might help distinguish sterile injury from infection. To study these events in primates we assayed banked serum from papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis deltaSterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to “severe” sepsis and death we studied animals where anthrax was pretreated with drotrecogin alfa (aPC), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against non-lethal E.coli bacteremia and against sterile tissue injury from Shiga-like toxin-1 (Stx1). bDNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Stx1 increased mtDNA but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sub-lethal E.coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal anthrax challenge (n=4) bDNA increased transiently but mtDNA levels remained elevated until death, consistent with persistent septic tissue damage after bacterial clearance. Critically, aPC pre-treatment (n=4) allowed mtDNA levels to decay after bacterial clearance with sparing of organ function and survival. In summary, host tissue injury correlates with mtDNA whether infective or sterile. mtDNA and bDNA PCRs can quantify tissue injury incurred by septic or sterile mechanisms and suggest the source of SIRS of unknown origin. PMID:23247122

Treatment of hyperfunctioning thyroid nodules with percutaneous ethanol injection: Eight years' experience.

PubMed

Monzani, F; Caraccio, N; Goletti, O; Casolaro, A; Lippolis, P V; Cavina, E; Miccoli, P

1998-01-01

The aim of our study was to define the long-term efficacy and safety of percutaneous ethanol injection (PEI) for the treatment of autonomous thyroid nodule (ATN), and to optimise the clinical usefulness of such a therapy. We treated 132 patients with ATN (30 M and 102 F, aged 47.5+/-12.9 years; mean+/-SD), in case other established treatments were refused or contraindicated. Eighty-five patients were affected by toxic adenoma and 47 suffered from pre-toxic nodules. Ethanol was administered weekly under sonographic control, in 7 sessions (range 2-16). During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. Three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra nodular tissue uptake, along with elevated free thyroid hormone and undetectable TSH levels); partial cure (normal free thyroid hormone and low/undetectable TSH levels); complete cure (normal thyroid hormone and TSH levels; restored extra nodular uptake). The patients were followed for up to 8.5 years (median 76 months). PEI therapy was well tolerated by all patients though a mild to moderate local pain occurred in about 30% of sessions. Complete cure was achieved in all pre-toxic patients and in 60 (70.6%) patients with toxic adenoma, while partial cure was observed in 11 cases (12.9%) and failure in 14 (16.5%). A significant shrinkage of nodule volume was observed in all patients (p = 0.0001), while those with toxic nodules larger than 30 mL showed a significantly lower response rate to PEI (p < 0.05). At controls, only one patient developed subclinical hypothyroidism while, among partially cured patients, five relapsed. The administration of methimazole and/or propranolol did not modify PEI outcome. In conclusion, we suggest that PEI therapy may be the treatment of choice in patients with pre-toxic thyroid adenoma where therapy is least necessary- despite the nodule volume. Though ethanol injection therapy of toxic thyroid nodules may be troublesome for the need of multiple sessions, it appears an effective alternative procedure in patients at poor surgical risk, and in younger patients in whom radioiodine is contraindicated. Since a special technical skill in intervention procedures is required, PEI therapy may be suitable only for patients living nearby a trained centre.

[GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2015)].

PubMed

2015-10-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients. To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America. In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines update previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Undetected psychiatric morbidity among HIV/AIDS patients attending Comprehensive Care Clinic (CCC) in Nairobi Kenya: towards an integrated mental health care.

PubMed

Ng'ang'a, Pauline W; Mathai, Muthoni; Obondo, Anne; Mutavi, Teresia; Kumar, Manasi

2018-01-01

Psychiatric morbidity is commonly associated with HIV disease and may have adverse effects. This aspect may be overlooked at comprehensive HIV care centers in Low and Middle-Income Countries. The aim of this study was to determine the prevalence of undetected psychiatric morbidity among HIV/AIDS adult patients attending Comprehensive Care Centre in a semi-urban clinic, in Nairobi, Kenya. Descriptive cross-sectional study of adult HIV patients not receiving any psychiatric treatment was conducted. The participants consisted of consecutive sample of adults ( n  = 245) attending HIV Comprehensive Care Clinic at Kangemi Health Centre, Nairobi. The Mini International Neuropsychiatric Interview (MINI) was administered to screen for undetected psychiatric morbidity. Socio-demographic characteristics were recorded in a questionnaire. Sample descriptive analysis was performed and prevalence of undetected psychiatric morbidity calculated. Chi-square test for independence was used to examine the associations between patient characteristics and undetected morbidity. Multivariable logistic regression analysis was performed to determine independent predictors of undetected psychiatric morbidity. The mean age of our participants was 37.3 years (SD 9.2) Three-quarters (75.9%) of participants were females and median duration of HIV illness was 5 years. The prevalence of (previously undetected) psychiatric morbidity was 71.4% (95% CI 65.3-77). The leading psychiatric disorders were MDD (32.2%), PTSD (18.4%), Dysthymia (17.6%), and OCD (17.6%). Overall psychiatric morbidity was associated with low income (

A Latent Transition Model with Logistic Regression

ERIC Educational Resources Information Center

Chung, Hwan; Walls, Theodore A.; Park, Yousung

2007-01-01

Latent transition models increasingly include covariates that predict prevalence of latent classes at a given time or transition rates among classes over time. In many situations, the covariate of interest may be latent. This paper describes an approach for handling both manifest and latent covariates in a latent transition model. A Bayesian…

Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young Men Who Have Sex with Men and Transgender Women in Chicago: Implications for Epidemiology, Care, and Prevention.

PubMed

Mustanski, Brian; Ryan, Daniel T; Remble, Thomas A; D'Aquila, Richard T; Newcomb, Michael E; Morgan, Ethan

2018-04-10

Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (< 200 copies/mL) via study-specific laboratory testing. Concordance between self-report and medical record VL values was 80% and between self-report and study-specific laboratory testing was 73%; 34% of participants with a detectable study-specific VL self-reported an undetectable VL at last medical visit, and another 28% reported not knowing their VL status. Periods of lapsed viral suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.

Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience.

PubMed

de la Taille, A; Hayek, O; Benson, M C; Bagiella, E; Olsson, C A; Fatal, M; Katz, A E

2000-01-01

Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.

Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal.

PubMed

Vallejo Casas, Juan A; Mena Bares, Luisa M; Gálvez Moreno, Maria A; Moreno Ortega, Estefanía; Marlowe, Robert J; Maza Muret, Francisco R; Albalá González, María D

2016-06-01

Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.

Verification Failures: What to Do When Things Go Wrong

NASA Astrophysics Data System (ADS)

Bertacco, Valeria

Every integrated circuit is released with latent bugs. The damage and risk implied by an escaped bug ranges from almost imperceptible to potential tragedy; unfortunately it is impossible to discern within this range before a bug has been exposed and analyzed. While the past few decades have witnessed significant efforts to improve verification methodology for hardware systems, these efforts have been far outstripped by the massive complexity of modern digital designs, leading to product releases for which an always smaller fraction of system's states has been verified. The news of escaped bugs in large market designs and/or safety critical domains is alarming because of safety and cost implications (due to replacements, lawsuits, etc.).

Knowledgeable Neighbors: a mobile clinic model for disease prevention and screening in underserved communities.

PubMed

Hill, Caterina; Zurakowski, David; Bennet, Jennifer; Walker-White, Rainelle; Osman, Jamie L; Quarles, Aaron; Oriol, Nancy

2012-03-01

The Family Van mobile health clinic uses a "Knowledgeable Neighbor" model to deliver cost-effective screening and prevention activities in underserved neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model and used operational data collected from 2006 to 2009 to evaluate the service. The Family Van successfully reached mainly minority low-income men and women. Of the clients screened, 60% had previously undetected elevated blood pressure, 14% had previously undetected elevated blood glucose, and 38% had previously undetected elevated total cholesterol. This represents an important model for reaching underserved communities to deliver proven cost-effective prevention activities, both to help control health care costs and to reduce health disparities.

Array coding for large data memories

NASA Technical Reports Server (NTRS)

Tranter, W. H.

1982-01-01

It is pointed out that an array code is a convenient method for storing large quantities of data. In a typical application, the array consists of N data words having M symbols in each word. The probability of undetected error is considered, taking into account three symbol error probabilities which are of interest, and a formula for determining the probability of undetected error. Attention is given to the possibility of reading data into the array using a digital communication system with symbol error probability p. Two different schemes are found to be of interest. The conducted analysis of array coding shows that the probability of undetected error is very small even for relatively large arrays.

MO-D-213-02: Quality Improvement Through a Failure Mode and Effects Analysis of Pediatric External Beam Radiotherapy

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

Gray, J; Lukose, R; Bronson, J

2015-06-15

Purpose: To conduct a failure mode and effects analysis (FMEA) as per AAPM Task Group 100 on clinical processes associated with teletherapy, and the development of mitigations for processes with identified high risk. Methods: A FMEA was conducted on clinical processes relating to teletherapy treatment plan development and delivery. Nine major processes were identified for analysis. These steps included CT simulation, data transfer, image registration and segmentation, treatment planning, plan approval and preparation, and initial and subsequent treatments. Process tree mapping was utilized to identify the steps contained within each process. Failure modes (FM) were identified and evaluated with amore » scale of 1–10 based upon three metrics: the severity of the effect, the probability of occurrence, and the detectability of the cause. The analyzed metrics were scored as follows: severity – no harm = 1, lethal = 10; probability – not likely = 1, certainty = 10; detectability – always detected = 1, undetectable = 10. The three metrics were combined multiplicatively to determine the risk priority number (RPN) which defined the overall score for each FM and the order in which process modifications should be deployed. Results: Eighty-nine procedural steps were identified with 186 FM accompanied by 193 failure effects with 213 potential causes. Eighty-one of the FM were scored with a RPN > 10, and mitigations were developed for FM with RPN values exceeding ten. The initial treatment had the most FM (16) requiring mitigation development followed closely by treatment planning, segmentation, and plan preparation with fourteen each. The maximum RPN was 400 and involved target delineation. Conclusion: The FMEA process proved extremely useful in identifying previously unforeseen risks. New methods were developed and implemented for risk mitigation and error prevention. Similar to findings reported for adult patients, the process leading to the initial treatment has an associated high risk.« less

Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-pacific hepatitis C virus genotype 1 non-responders/relapsers

PubMed Central

Sukeepaisarnjaroen, Wattana; Pham, Tri; Tanwandee, Tewesak; Nazareth, Saroja; Galhenage, Sam; Mollison, Lindsay; Totten, Leanne; Wigg, Alan; Altus, Rosalie; Colman, Anton; Morales, Brenda; Mason, Sue; Jones, Tracey; Leembruggen, Nadine; Fragomelli, Vince; Sendall, Cheryl; Guan, Richard; Sutedja, Dede; Tan, Soek Siam; Dan, Yock Young; Lee, Yin Mei; Luman, Widjaja; Teo, Eng Kiong; Than, Yin Min; Piratvisuth, Teerha; Lim, Seng Gee

2015-01-01

AIM: To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia. METHODS: The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures. Participating physicians were invited to contribute data from their patients: baseline characteristics, on-treatment responses, sustained virological response at week 12 (SVR12), and safety were collected and analysed. Multivariate analysis was performed to determine predictors of response. RESULTS: 150 patients were enrolled from Australia, Malaysia, Singapore and Thailand (Asians = 86, Caucasians = 63). Overall SVR12 was 61% (Asians = 59.3%, Caucasians = 63.5%). SVR12 was higher in relapsers (78%) compared with non-responders (34%). On-treatment responses predicted SVR, with undetectable HCVRNA at week 4, 8 and 12 leading to SVR12s of 100%, 87%, and 82% respectively, and detectable HCVRNA at week 4, 8 and 12, leading to SVR12s of 58%, 22% and 6% respectively. Asian patients were similar to Caucasian patients with regards to on-treatment responses. Patients with cirrhosis (n = 69) also behaved in the same manner with regards to on-treatment responses. Those with the IL28B CC genotype (80%) had higher SVRs than those with the CT/TT (56%) genotype (P = 0.010). Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR. Serious adverse events occurred in 18.6%: sepsis (2%), decompensation (2.7%) and blood transfusion (14%). Discontinuations occurred in 30.7%, with 18.6% fulfilling stopping rules. CONCLUSION: Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80% if they have good on-treatment responses; however, discontinuations occurred in 30% because of virological failure or adverse events. PMID:26229408

Estimating the proportion of pneumonia attributable to pneumococcus in Kenyan adults: latent class analysis.

PubMed

Jokinen, Jukka; Scott, J Anthony G

2010-09-01

Community-acquired pneumonia is a common cause of hospitalization among African adults, and Streptococcus pneumoniae is assumed to be a frequent cause. Pneumococcal conjugate vaccine is currently being introduced into childhood immunization programs in Africa. The case for adult vaccination is dependent on the contribution of the pneumococcus to the hospital pneumonia burden. Pneumococcal diagnosis is complex because there is no gold standard, and culture methods are invalidated by antibiotic use. We used latent class analysis to estimate the proportion of pneumonia episodes caused by pneumococcus. Furthermore, we extended this methodology to evaluate the effect of antimicrobial treatment on test accuracies and the prevalence of the disease. The study combined data from 5 validation studies of pneumococcal diagnostic tests performed on 281 Kenyan adults with pneumonia. The proportion of pneumonia episodes attributable to pneumococcus was 0.46 (95% confidence interval = 0.36-0.57). Failure to account for the effect of antimicrobial exposure underestimates this proportion as 0.32. A history of antibiotic exposure was a poor predictor of antimicrobial activity in patients' urine. Blood culture sensitivity for pneumococcus was estimated at 0.24 among patients with antibiotic exposure, and 0.75 among those without. The large contribution of pneumococcus to adult pneumonia provides a strong case for the investigation of pneumococcal vaccines in African adults.

Bias correction in the hierarchical likelihood approach to the analysis of multivariate survival data.

PubMed

Jeon, Jihyoun; Hsu, Li; Gorfine, Malka

2012-07-01

Frailty models are useful for measuring unobserved heterogeneity in risk of failures across clusters, providing cluster-specific risk prediction. In a frailty model, the latent frailties shared by members within a cluster are assumed to act multiplicatively on the hazard function. In order to obtain parameter and frailty variate estimates, we consider the hierarchical likelihood (H-likelihood) approach (Ha, Lee and Song, 2001. Hierarchical-likelihood approach for frailty models. Biometrika 88, 233-243) in which the latent frailties are treated as "parameters" and estimated jointly with other parameters of interest. We find that the H-likelihood estimators perform well when the censoring rate is low, however, they are substantially biased when the censoring rate is moderate to high. In this paper, we propose a simple and easy-to-implement bias correction method for the H-likelihood estimators under a shared frailty model. We also extend the method to a multivariate frailty model, which incorporates complex dependence structure within clusters. We conduct an extensive simulation study and show that the proposed approach performs very well for censoring rates as high as 80%. We also illustrate the method with a breast cancer data set. Since the H-likelihood is the same as the penalized likelihood function, the proposed bias correction method is also applicable to the penalized likelihood estimators.

Nonunion After Clavicle Osteosynthesis: High Incidence of Propionibacterium acnes.

PubMed

Gausden, Elizabeth B; Villa, Jordan; Warner, Stephen J; Redko, Mariya; Pearle, Andrew; Miller, Andy; Henry, Michael; Lorich, Dean G; Helfet, David L; Wellman, David S

2017-04-01

The objective of this study was to review the etiology of clavicle nonunions after osteosynthesis and investigate the outcomes of a treatment with a single-stage revision. Retrospective case series. Orthopaedic specialty hospital. Twenty cases of nonunion after osteosynthesis of the clavicle were identified. The average age was 44 years (±13 years). In 9 cases, there was catastrophic implant failure that prompted the revision surgery. In the 18 cases in which cultures were taken, 15 of the 18 (83%) were treated as infections with a course of antibiotics. In 14 cases, the cultures were positive for Propionibacterium acnes. Fifteen patients were treated with a prolonged course of antibiotics. Eighteen patients had follow-up, and the average time to radiographic union was 22 weeks. There were no cases of nonunion after revision surgery. There is a high rate of positive cultures in cases of nonunion after osteosynthesis of the clavicle. This suggests the etiology of midshaft clavicle nonunions may result from a combination of suboptimal mechanical fixation and latent infection. Our treatment protocol of superior and anterior plating, interfragmentary fixation, bone grafting, and appropriate antimicrobial treatment of latent infections has resulted in 100% union rate. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The causes of and factors associated with prescribing errors in hospital inpatients: a systematic review.

PubMed

Tully, Mary P; Ashcroft, Darren M; Dornan, Tim; Lewis, Penny J; Taylor, David; Wass, Val

2009-01-01

Prescribing errors are common, they result in adverse events and harm to patients and it is unclear how best to prevent them because recommendations are more often based on surmized rather than empirically collected data. The aim of this systematic review was to identify all informative published evidence concerning the causes of and factors associated with prescribing errors in specialist and non-specialist hospitals, collate it, analyse it qualitatively and synthesize conclusions from it. Seven electronic databases were searched for articles published between 1985-July 2008. The reference lists of all informative studies were searched for additional citations. To be included, a study had to be of handwritten prescriptions for adult or child inpatients that reported empirically collected data on the causes of or factors associated with errors. Publications in languages other than English and studies that evaluated errors for only one disease, one route of administration or one type of prescribing error were excluded. Seventeen papers reporting 16 studies, selected from 1268 papers identified by the search, were included in the review. Studies from the US and the UK in university-affiliated hospitals predominated (10/16 [62%]). The definition of a prescribing error varied widely and the included studies were highly heterogeneous. Causes were grouped according to Reason's model of accident causation into active failures, error-provoking conditions and latent conditions. The active failure most frequently cited was a mistake due to inadequate knowledge of the drug or the patient. Skills-based slips and memory lapses were also common. Where error-provoking conditions were reported, there was at least one per error. These included lack of training or experience, fatigue, stress, high workload for the prescriber and inadequate communication between healthcare professionals. Latent conditions included reluctance to question senior colleagues and inadequate provision of training. Prescribing errors are often multifactorial, with several active failures and error-provoking conditions often acting together to cause them. In the face of such complexity, solutions addressing a single cause, such as lack of knowledge, are likely to have only limited benefit. Further rigorous study, seeking potential ways of reducing error, needs to be conducted. Multifactorial interventions across many parts of the system are likely to be required.

Beliefs about Lying and Spreading of Dishonesty: Undetected Lies and Their Constructive and Destructive Social Dynamics in Dice Experiments

PubMed Central

Rauhut, Heiko

2013-01-01

Field experiments have shown that observing other people littering, stealing or lying can trigger own misconduct, leading to a decay of social order. However, a large extent of norm violations goes undetected. Hence, the direction of the dynamics crucially depends on actors’ beliefs regarding undetected transgressions. Because undetected transgressions are hardly measureable in the field, a laboratory experiment was developed, where the complete prevalence of norm violations, subjective beliefs about them, and their behavioral dynamics is measurable. In the experiment, subjects could lie about their monetary payoffs, estimate the extent of liars in their group and make subsequent lies contingent on information about other people’s lies. Results show that informed people who underestimate others’ lying increase own lying more than twice and those who overestimate, decrease it by more than half compared to people without information about others’ lies. This substantial interaction puts previous results into perspective, showing that information about others’ transgressions can trigger dynamics in both directions: the spreading of normative decay and restoring of norm adherence. PMID:24236007

Validating a self-report measure of HIV viral suppression: an analysis of linked questionnaire and clinical data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study.

PubMed

Carter, Allison; de Pokomandy, Alexandra; Loutfy, Mona; Ding, Erin; Sereda, Paul; Webster, Kath; Nicholson, Valerie; Beaver, Kerrigan; Hogg, Robert S; Kaida, Angela

2017-03-24

We assessed the validity of a self-report measure of undetectable viral load (VL) among women with HIV in British Columbia (BC), Canada. Questionnaire data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study was linked with population-based clinical data from the BC Centre for Excellence in HIV/AIDS. Self-reported undetectable VL was assessed by the question: "What was your most recent VL, undetectable (i.e. <50 copies/mL) or detectable (i.e. ≥50 copies/mL)?" Laboratory measurements of VL <50 copies/mL (closest to/before study visit) were the criterion for validity analyses. We measured positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-). Of 356 participants, 99% were linked to clinical data. Those unlinked (n = 1), missing self-report VL (n = 18), or missing self-report and laboratory VL (n = 1) were excluded. Among the remaining 336: median age was 44 (IQR 37-51); 96% identified as cis-gender; 84% identified as heterosexual; and 45% identified as Indigenous, 40% White, 8% African, Caribbean, or Black, and 8% other/multiple ethnicities. Overall, 85% self-reported having an undetectable VL while 82% had clinical data indicating viral suppression. The PPV was 93.7 (95% CI 90.2-96.2) indicating that 94% of women who self-reported being undetectable truly were. The NPV was 80.4 (95% CI 66.9-90.2). LR+ was 3.2 (2.1-4.6) and LR- was 0.05 (0.03-0.10). Our self-report measure assessing undetectable VL strongly predicted true viral suppression among Canadian women with HIV. This measure can be used in research settings without laboratory data in regions with high rates of VL testing and suppression.

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

Heterologous production of a ginsenoside saponin (compound K) and its precursors in transgenic tobacco impairs the vegetative and reproductive growth.

PubMed

Gwak, Yu Shin; Han, Jung Yeon; Adhikari, Prakash Babu; Ahn, Chang Ho; Choi, Yong Eui

2017-06-01

Production of compound K (a ginsenoside saponin) and its precursors in transgenic tobacco resulted in stunted growth and seed set failure, which may be caused by strong autotoxicity of heterologously produced phytochemicals against the tobacco itself. Panax ginseng roots contain various saponins (ginsenosides), which are major bioactive compounds. A monoglucosylated saponin, compound K (20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol), has high medicinal and cosmetic values but is present in undetectable amounts in naturally grown ginseng roots. The production of compound K (CK) requires complicated deglycosylation of ginsenosides using physicochemical and/or enzymatic degradation. In this work, we report the production of CK in transgenic tobacco by co-overexpressing three genes (PgDDS, CYP716A47 and UGT71A28) isolated from P. ginseng. Introduction and expression of the transgenes in tobacco lines were confirmed by genomic PCR and RT-PCR. All the lines of transgenic tobacco produced CK including its precursors, protopanaxadiol and dammarenediol-II (DD). The concentrations of CK in the leaves ranged from 1.55 to 2.64 µg/g dry weight, depending on the transgenic line. Interestingly, production of CK in tobacco brought stunted plant growth and gave rise to seed set failure. This seed set failure was caused by both long-styled flowers and abnormal pollen development in transgenic tobacco. Both CK and DD treatments highly suppressed in vitro germination and tube growth in wild-type pollens. Based on these results, metabolic engineering for CK production in transgenic tobacco was successfully achieved, but the production of CK and its precursors in tobacco severely affects vegetative and reproductive growth due to the cytotoxicity of phytochemicals that are heterologously produced in transgenic tobacco.

Residual strength of thin panels with cracks

NASA Technical Reports Server (NTRS)

Madenci, Erdogan

1994-01-01

The previous design philosophies involving safe life, fail-safe and damage tolerance concepts become inadequate for assuring the safety of aging aircraft structures. For example, the failure mechanism for the Aloha Airline accident involved the coalescence of undetected small cracks at the rivet holes causing a section of the fuselage to peel open during flight. Therefore, the fuselage structure should be designed to have sufficient residual strength under worst case crack configurations and in-flight load conditions. Residual strength is interpreted as the maximum load carrying capacity prior to unstable crack growth. Internal pressure and bending moment constitute the two major components of the external loads on the fuselage section during flight. Although the stiffeners in the form of stringers, frames and tear straps sustain part of the external loads, the significant portion of the load is taken up by the skin. In the presence of a large crack in the skin, the crack lips bulge out with considerable yielding; thus, the geometric and material nonlinearities must be included in the analysis for predicting residual strength. Also, these nonlinearities do not permit the decoupling of in-plane and out-of-plane bending deformations. The failure criterion combining the concepts of absorbed specific energy and strain energy density addresses the aforementioned concerns. The critical absorbed specific energy (local toughness) for the material is determined from the global specimen response and deformation geometry based on the uniaxial tensile test data and detailed finite element modeling of the specimen response. The use of the local toughness and stress-strain response at the continuum level eliminates the size effect. With this critical parameter and stress-strain response, the finite element analysis of the component by using STAGS along with the application of this failure criterion provides the stable crack growth calculations for residual strength predictions.

The probability of laser caused ocular injury to the aircrew of undetected aircraft violating the exclusion zone about the airborne aura LIDAR.

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

Augustoni, Arnold L.

2006-12-01

The probability of a laser caused ocular injury, to the aircrew of an undetected aircraft entering the exclusion zone about the AURA LIDAR airborne platform with the possible violation of the Laser Hazard Zone boundary, was investigated and quantified for risk analysis and management.

Is the cervical spine clear? Undetected cervical fractures diagnosed only at autopsy.

PubMed

Sweeney, J F; Rosemurgy, A S; Gill, S; Albrink, M H

1992-10-01

Undetected cervical-spine injuries are a nemesis to both trauma surgeons and emergency physicians. Radiographic protocols have been developed to avoid missing cervical-spine fractures but are not fail-safe. Three case reports of occult cervical fractures documented at autopsy in the face of normal cervical-spine radiographs and computerized tomography scans are presented.

Knowledgeable Neighbors:A Mobile Clinic Model for Disease Prevention and Screening in Underserved Communities

PubMed Central

Zurakowski, David; Bennet, Jennifer; Walker-White, Rainelle; Osman, Jamie L.; Quarles, Aaron; Oriol, Nancy

2012-01-01

The Family Van mobile health clinic uses a “Knowledgeable Neighbor” model to deliver cost-effective screening and prevention activities in underserved neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model and used operational data collected from 2006 to 2009 to evaluate the service. The Family Van successfully reached mainly minority low-income men and women. Of the clients screened, 60% had previously undetected elevated blood pressure, 14% had previously undetected elevated blood glucose, and 38% had previously undetected elevated total cholesterol. This represents an important model for reaching underserved communities to deliver proven cost-effective prevention activities, both to help control health care costs and to reduce health disparities. PMID:22390503

A Flexible Latent Class Approach to Estimating Test-Score Reliability

ERIC Educational Resources Information Center

van der Palm, Daniël W.; van der Ark, L. Andries; Sijtsma, Klaas

2014-01-01

The latent class reliability coefficient (LCRC) is improved by using the divisive latent class model instead of the unrestricted latent class model. This results in the divisive latent class reliability coefficient (DLCRC), which unlike LCRC avoids making subjective decisions about the best solution and thus avoids judgment error. A computational…

Optimization-Based Model Fitting for Latent Class and Latent Profile Analyses

ERIC Educational Resources Information Center

Huang, Guan-Hua; Wang, Su-Mei; Hsu, Chung-Chu

2011-01-01

Statisticians typically estimate the parameters of latent class and latent profile models using the Expectation-Maximization algorithm. This paper proposes an alternative two-stage approach to model fitting. The first stage uses the modified k-means and hierarchical clustering algorithms to identify the latent classes that best satisfy the…

Estimating and Interpreting Latent Variable Interactions: A Tutorial for Applying the Latent Moderated Structural Equations Method

ERIC Educational Resources Information Center

Maslowsky, Julie; Jager, Justin; Hemken, Douglas

2015-01-01

Latent variables are common in psychological research. Research questions involving the interaction of two variables are likewise quite common. Methods for estimating and interpreting interactions between latent variables within a structural equation modeling framework have recently become available. The latent moderated structural equations (LMS)…

Modeling Nonlinear Change via Latent Change and Latent Acceleration Frameworks: Examining Velocity and Acceleration of Growth Trajectories

ERIC Educational Resources Information Center

Grimm, Kevin; Zhang, Zhiyong; Hamagami, Fumiaki; Mazzocco, Michele

2013-01-01

We propose the use of the latent change and latent acceleration frameworks for modeling nonlinear growth in structural equation models. Moving to these frameworks allows for the direct identification of "rates of change" and "acceleration" in latent growth curves--information available indirectly through traditional growth…

On the explaining-away phenomenon in multivariate latent variable models.

PubMed

van Rijn, Peter; Rijmen, Frank

2015-02-01

Many probabilistic models for psychological and educational measurements contain latent variables. Well-known examples are factor analysis, item response theory, and latent class model families. We discuss what is referred to as the 'explaining-away' phenomenon in the context of such latent variable models. This phenomenon can occur when multiple latent variables are related to the same observed variable, and can elicit seemingly counterintuitive conditional dependencies between latent variables given observed variables. We illustrate the implications of explaining away for a number of well-known latent variable models by using both theoretical and real data examples. © 2014 The British Psychological Society.

NREL/NASA Internal Short-Circuit Instigator in Lithium Ion Cells; NREL (National Renewable Energy Laboratory)

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

Long, Dirk; Ireland, John; Pesaran, Ahmad

NREL has developed a device to test one of the most challenging failure mechanisms of lithium-ion (Li-ion) batteries -- a battery internal short circuit. Many members of the technical community believe that this type of failure is caused by a latent flaw that results in a short circuit between electrodes during use. As electric car manufacturers turn to Li-ion batteries for energy storage, solving the short circuit problem becomes more important. To date, no reliable and practical method exists to create on-demand internal shorts in Li-ion cells that produce a response that is relevant to the ones produced by fieldmore » failures. NREL and NASA have worked to establish an improved ISC cell-level test method that simulates an emergent internal short circuit, is capable of triggering the four types of cell internal shorts, and produces consistent and reproducible results. Internal short circuit device design is small, low-profile and implantable into Li-ion cells, preferably during assembly. The key component is an electrolyte-compatible phase change material (PCM). The ISC is triggered by heating the cell above PCM melting temperature (presently 40 degrees C – 60 degrees C). In laboratory testing, the activated device can handle currents in excess of 300 A to simulate hard shorts (< 2 mohms). Phase change from non-conducting to conducting has been 100% successful during trigger tests.« less

The algebraic theory of latent projectors in lambda matrices

NASA Technical Reports Server (NTRS)

Denman, E. D.; Leyva-Ramos, J.; Jeon, G. J.

1981-01-01

Multivariable systems such as a finite-element model of vibrating structures, control systems, and large-scale systems are often formulated in terms of differential equations which give rise to lambda matrices. The present investigation is concerned with the formulation of the algebraic theory of lambda matrices and the relationship of latent roots, latent vectors, and latent projectors to the eigenvalues, eigenvectors, and eigenprojectors of the companion form. The chain rule for latent projectors and eigenprojectors for the repeated latent root or eigenvalues is given.

Latent Transition Analysis with a Mixture Item Response Theory Measurement Model

ERIC Educational Resources Information Center

Cho, Sun-Joo; Cohen, Allan S.; Kim, Seock-Ho; Bottge, Brian

2010-01-01

A latent transition analysis (LTA) model was described with a mixture Rasch model (MRM) as the measurement model. Unlike the LTA, which was developed with a latent class measurement model, the LTA-MRM permits within-class variability on the latent variable, making it more useful for measuring treatment effects within latent classes. A simulation…

Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

PubMed Central

Li, Lihong; Li, Zhuoran; Wang, Erlin; Yang, Rui; Xiao, Yu; Han, Hongbo; Lang, Fengchao; Li, Xin; Xia, Yujie; Gao, Feng; Li, Qihan; Fraser, Nigel W.

2015-01-01

ABSTRACT Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG infections. Taken together, these observations suggest that the tree shrew TG infection differs significantly from the existing rodent models. IMPORTANCE Herpes simplex viruses (HSVs) establish lifelong infection in more than 80% of the human population, and their reactivation leads to oral and genital herpes. Currently, rodent models are the preferred models for latency studies. Rodents are distant from primates and may not fully represent human latency. The tree shrew is a small mammal, a prosimian primate, indigenous to southwest Asia. In an attempt to further develop the tree shrew as a useful model to study herpesvirus infection, we studied the establishment of latency and reactivation of HSV-1 in tree shrews following ocular inoculation. We found that the latent virus, which resides in the sensory neurons of the trigeminal ganglion, could be stress reactivated to produce infectious virus, following explant cocultivation and that spontaneous reactivation could be detected by cell culture of tears. Interestingly, the tree shrew model is quite different from the mouse model of HSV infection, in that the virus exhibited only a mild acute infection following inoculation with no detectable infectious virus from the sensory neurons. The mild infection may be more similar to human infection in that the sensory neurons continue to function after herpes reactivation and the affected skin tissue does not lose sensation. Our findings suggest that the tree shrew is a viable model to study HSV latency. PMID:26512084

The complexity of team training: what we have learned from aviation and its applications to medicine

PubMed Central

Hamman, W

2004-01-01

Errors in health care that compromise patient safety are tied to latent failures in the structure and function of systems. Teams of people perform most care delivered today, yet training often remains focused on individual responsibilities. Training programmes for all healthcare workers need to increase the educational experience of working in interdisciplinary teams. The complexities of team training require a multifunctional (systems) approach, which crosses organisational divisions to allow communication, accountability, and creation and maintenance of interdisciplinary teams. This report identifies challenges for medical education in performing the research, identifying performance measurements, and modifying educational curricula for the advancement of interdisciplinary teams, based on the complexity of team training identified in commercial aviation. PMID:15465959

When the Brain Takes a Break: A Model-Based Analysis of Mind Wandering

PubMed Central

Boekel, Wouter; Tucker, Adrienne M.; Turner, Brandon M.; Heathcote, Andrew; Forstmann, Birte U.

2014-01-01

Mind wandering is an ubiquitous phenomenon in everyday life. In the cognitive neurosciences, mind wandering has been associated with several distinct neural processes, most notably increased activity in the default mode network (DMN), suppressed activity within the anti-correlated (task-positive) network (ACN), and changes in neuromodulation. By using an integrative multimodal approach combining machine-learning techniques with modeling of latent cognitive processes, we show that mind wandering in humans is characterized by inefficiencies in executive control (task-monitoring) processes. This failure is predicted by a single-trial signature of (co)activations in the DMN, ACN, and neuromodulation, and accompanied by a decreased rate of evidence accumulation and response thresholds in the cognitive model. PMID:25471568

Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature.

PubMed

Woods, K A; Camacho-Hübner, C; Barter, D; Clark, A J; Savage, M O

1997-11-01

The first human case of a homozygous molecular defect in the gene encoding insulin-like growth factor I (IGF-I) is described. The patient was a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild mental retardation. Endocrine evaluation of the growth hormone (GH)--IGF-I axis revealed elevated GH secretion, undetectable serum IGF-I and normal serum IGF-binding protein-3, acid-labile subunit, and GH-binding activity. Analysis of the IGF-I gene revealed a homozygous partial IGF-I gene deletion involving exons 4 and 5, which encodes a severely truncated mature IGF-I peptide. This patient demonstrates that complete disruption of the IGF-I gene in man is compatible with life, and indicates a major role for IGF-I in human fetal growth. In addition, his neurological abnormalities suggest that IGF-I may be involved in central nervous system development.

Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles

NASA Astrophysics Data System (ADS)

Lukianova-Hleb, Ekaterina Y.; Kim, Yoo-Shin; Belatsarkouski, Ihor; Gillenwater, Ann M.; O'Neill, Brian E.; Lapotko, Dmitri O.

2016-06-01

Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures.

Intraoperative detection and elimination of microscopic tumors in head and neck (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lukianova-Hleb, Ekaterina Y.; Kim, Yoo-Shin; Belatsarkouski, Ihar; Hanna, Ehab Y.; Gillenwater, Ann M.; O'Neill, Brian; Lapotko, Dmitri

2016-02-01

Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, whereas removal of important normal tissues causes excessive morbidity. We report plasmonic nanobubble (PNB) surgical technology to intraoperatively detect and eliminate MRD in surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumor with gold colloids and locally-applied near-infrared low energy short laser pulse, and were simultaneously detected with acoustic probe. In mouse models of head and neck squamous cell carcinoma, single cancer cells and MRD (undetectable with standard histological methods) were instantaneously non-invasively detected in solid tissue in surgical bed. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumor-free survival. In unresectable MRD, PNB nano-surgery improved survival by two-fold compared to standard surgery. PNB metrics correlated with the tumor recurrence rate. PNB surgical technology precisely detects and immediately eliminates MRD at macro- and micro-scale in a simple and safe intraoperative procedure.

Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

PubMed

Jindracek, Lauren; Stark, Jennifer

2017-01-01

Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

Measurement of fault latency in a digital avionic miniprocessor

NASA Technical Reports Server (NTRS)

Mcgough, J. G.; Swern, F. L.

1981-01-01

The results of fault injection experiments utilizing a gate-level emulation of the central processor unit of the Bendix BDX-930 digital computer are presented. The failure detection coverage of comparison-monitoring and a typical avionics CPU self-test program was determined. The specific tasks and experiments included: (1) inject randomly selected gate-level and pin-level faults and emulate six software programs using comparison-monitoring to detect the faults; (2) based upon the derived empirical data develop and validate a model of fault latency that will forecast a software program's detecting ability; (3) given a typical avionics self-test program, inject randomly selected faults at both the gate-level and pin-level and determine the proportion of faults detected; (4) determine why faults were undetected; (5) recommend how the emulation can be extended to multiprocessor systems such as SIFT; and (6) determine the proportion of faults detected by a uniprocessor BIT (built-in-test) irrespective of self-test.

[Uncovering an undetected homicide by exhumation].

PubMed

Grellner, Wolfgang

2009-01-01

The problems of postmortem examinations and the associated dark figure of undetected homicides are well known and have been repeatedly discussed in Germany. The article deals with the case of a 73-year-old woman whose death was initially certified as being natural ("sudden cardiac death"). When secondary suspicious circumstances turned up, an exhumation was ordered three weeks after the burial. At autopsy, signs of multiple blunt force to the occiput, the thorax and the upper extremities as well as compression of the neck were found. The findings proved foreign intervention and suggested death due to suffocation. In the court trial, the accused pleaded an accidental event (fall down stairs). He was sentenced to life imprisonment for murder. The presented case of homicide remained undetected at first, as due to the deceased's advanced age a natural death had been falsely assumed. An obviously very superficial external postmortem examination by the physician was probably the main reason for the misjudgement. The factors "advanced age" and "homicide leaving few external traces and no visible injuries" seem to present special problems and essentially contribute to the dark figure of undetected homicides. Physicians performing postmortem examinations and the general public should be made aware of the problem by regular further education and discussion.

Avoiding and Correcting Bias in Score-Based Latent Variable Regression with Discrete Manifest Items

ERIC Educational Resources Information Center

Lu, Irene R. R.; Thomas, D. Roland

2008-01-01

This article considers models involving a single structural equation with latent explanatory and/or latent dependent variables where discrete items are used to measure the latent variables. Our primary focus is the use of scores as proxies for the latent variables and carrying out ordinary least squares (OLS) regression on such scores to estimate…

Simple Estimators for the Simple Latent Class Mastery Testing Model. Twente Educational Memorandum No. 19.

ERIC Educational Resources Information Center

van der Linden, Wim J.

Latent class models for mastery testing differ from continuum models in that they do not postulate a latent mastery continuum but conceive mastery and non-mastery as two latent classes, each characterized by different probabilities of success. Several researchers use a simple latent class model that is basically a simultaneous application of the…

Fingerprint detection

DOEpatents

Saunders, George C.

1992-01-01

A method for detection and visualization of latent fingerprints is provided and includes contacting a substrate containing a latent print thereon with a colloidal metal composition for time sufficient to allow reaction of said colloidal metal composition with said latent print, and preserving or recording the observable print. Further, the method for detection and visualization of latent fingerprints can include contacting the metal composition-latent print reaction product with a secondary metal-containing solution for time sufficient to allow precipitation of said secondary metal thereby enhancing the visibility of the latent print, and preserving or recording the observable print.

Persistence of low levels of plasma viremia and of the latent reservoir in patients under ART: A fractional-order approach

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.

2017-02-01

Low levels of viral load are found in HIV-infected patients, after many years under successful suppressive anti-retroviral therapy (ART). The factors leading to this persistence are still under debate, but it is now more or less accepted that the latent reservoir may be crucial to the maintenance of this residual viremia. In this paper, we study the role of the latent reservoir in the persistence of the latent reservoir and of the plasma viremia in a fractional-order (FO) model for HIV infection. Our model assumes that (i) the latently infected cells may undergo bystander proliferation, without active viral production, (ii) the latent cell activation rate decreases with time on ART, (iii) the productively infected cells' death rate is a function of the infected cell density. The proposed model provides new insights on the role of the latent reservoir in the persistence of the latent reservoir and of the plasma virus. Moreover, the fractional-order derivative distinguishes distinct velocities in the dynamics of the latent reservoir and of plasma virus. The later may be used to better approximations of HIV-infected patients data. To our best knowledge, this is the first FO model that deals with the role of the latent reservoir in the persistence of low levels of viremia and of the latent reservoir.

Factors associated with perceived accuracy of the Undetectable = Untransmittable slogan among men who have sex with men: Implications for messaging scale-up and implementation.

PubMed

Rendina, H Jonathon; Parsons, Jeffrey T

2018-01-01

Recent research has shown high efficacy of HIV treatment for reducing the risk of HIV transmission to sexual partners. As the efficacy of treatment as prevention (TasP) has proliferated, a new messaging campaign, Undetectable = Untransmittable, has been gaining popularity. The purpose of this paper was to assess factors associated with the perceived accuracy of this TasP messaging strategy among a large and diverse sample of gay, bisexual, and other men who have sex with men (GBMSM) in order to inform subsequent efforts at large-scale and implementation of the HIV prevention message. We conducted a nationwide survey of GBMSM in the U.S. recruited from an online social networking site and a mobile sexual networking app. We analysed data from 12,222 GBMSM separately by HIV status to examine sociodemographic and behavioural factors associated with ratings of the accuracy of the Undetectable = Untransmittable message, which included the option to indicate not understanding what "undetectable" meant. Among HIV-negative and unknown men, multivariable linear regression indicated that being on pre-exposure prophylaxis (PrEP), identifying as gay or queer (versus bisexual or straight), recent serodiscordant condomless anal sex (CAS), testing every six months or more often, less concern about sexually transmitted infection (STI) infection, and lower perceived risk of HIV infection were the factors with the largest independent effect on rating the Undetectable = Untransmittable statement as more accurate. Fewer factors emerged as associated with accuracy ratings among HIV-positive participants-reporting an undetectable viral load, a lifetime acquired immune deficiency syndrome (AIDS) diagnosis, and lower concern about STI infection were the factors most strongly associated with rating the statement as more accurate. The findings of the current study highlight variability in the perceived accuracy of the Undetectable = Untransmittable message, suggesting potential subgroups who might benefit from targeted educational campaigns, perhaps broadcast utilizing sexual networking apps. Numerous factors, particularly among HIV-negative and unknown GBMSM, were associated with rating the message as more accurate. In particular, being on PrEP and testing regularly were two of the variables most strongly associated with higher accuracy ratings among HIV-negative GBMSM, suggesting HIV prevention services as potential points of intervention for increasing HIV knowledge and decreasing HIV stigma. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

PubMed

Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

2009-08-11

TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3+ regulatory T cells

PubMed Central

Tran, Dat Q.; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M.

2009-01-01

TGF-β family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-β is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFβ-binding protein (LTBP) to produce a large latent form. Latent TGF-β is also found on the surface of activated FOXP3+ regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-β to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-β and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-β expression on activated Tregs and recombinant latent TGF-β1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-β on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism. PMID:19651619

A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion.

PubMed

Liu, Yuehong; Li, Shufeng

2015-01-01

Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.

Association between latent toxoplasmosis and cognition in adults: a cross-sectional study.

PubMed

Gale, S D; Brown, B L; Erickson, L D; Berrett, A; Hedges, D W

2015-04-01

Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

Health-related quality of life is not impaired in children with undetected as well as diagnosed celiac disease: a large population based cross-sectional study.

PubMed

Myléus, Anna; Petersen, Solveig; Carlsson, Annelie; Hammarroth, Solveig; Högberg, Lotta; Ivarsson, Anneli

2014-05-05

Knowledge regarding the health-related quality of life (HRQoL) of children with celiac disease remains limited and inconclusive. We investigated the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii) clinically diagnosed celiac disease, and iii) without celiac disease. A school-based cross-sectional multicenter screening study invited 18 325 children, whereof 68% consented to participate. Participants provided a blood sample, which was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were elevated, a small intestinal biopsy verified the screening-detected celiac disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52 items instrument with proven reliability and validity. Scores were linearly transformed into a 0-100 scale with higher values indicating better HRQoL. Mean values with standard deviations (mean ± SD) were compared, and uni- and multivariate logistic regression models tested the odds of a low HRQoL among children with undetected or diagnosed celiac disease, respectively. Children with undetected celiac disease (n = 238) reported similar HRQoL as children without celiac disease (n = 12 037) (83.0 ± 11.0 vs. 82.5 ± 11.3, P = 0.51), and also similar HRQoL (82.2 ± 12.2, P = 0.28) to that of children with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment. Having undetected celiac disease did not increase the odds of low overall HRQoL, independent of sex, area of residence, study year and occurrence of gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10). Comparable results were seen for diagnosed celiac disease cases (adjusted odds ratio 1.11, 95% CI 0.67-1.85). Children with undetected celiac disease reported comparable HRQoL as their peers with diagnosed celiac disease, and those without celiac disease, when reporting prior to receiving the diagnosis through screening. Thus, children with celiac disease, both untreated and diagnosed, perceive their HRQoL as unimpaired by their disease.

[GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014)].

PubMed

2014-01-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: <350cells/μL, A-I; 350-500 cells/μL, A-II, and >500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines updates previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Application of a nanoflare probe specific to a latency associated transcript for isolation of KHV latently infected cells

PubMed Central

Reed, Aimee N.; Putman, Timothy; Sullivan, Christopher; Jin, Ling

2015-01-01

One of the unique features of herpesvirus infection is latent infection following an initial exposure, which is characterized by viral genome persistence in a small fraction of cells within the latently infected tissue. Investigation of the mechanisms of herpesvirus latency has been very challenging in tissues with only a small fraction of cells that are latently infected. Cyprinid herpesvirus 3, also known as koi herpesvirus (KHV), is an important and deadly pathogen of koi and common carp, Cyprinus carpio. Acute infection can cause up to 100% mortality in exposed fish, and fish that survive the infection become latently infected. KHV becomes latent in a small percentage of B lymphocytes and can reactivate under stressful conditions. During latency, KHV ORF6 transcript is expressed in the latently infected B lymphocytes. In order to study KHV latent infection in cells that are only latently infected, a nanoflare probe specific to ORF6 RNA was used to separate KHV latently infected cells from total peripheral white blood cells (WBC). Using the ORF6 nanoflare probe, less than 1% of peripheral WBC was isolated from KHV latently infected koi. When this enriched population of WBC was examined by real-time PCR specific for KHV, it was estimated that about 1 to 2 copies of viral genome persists in the sorted cells. In addition, KHV ORF6 transcript was shown to be the major transcript expressed during latency by RNA-seq analysis. This study demonstrated that an RNA nanoflare probe could be used to enrich latently infected cells, which can subsequently be used to investigate the molecular mechanisms of KHV latency. PMID:26087404

Cognitive and contextual influences in determination of latent fingerprint suitability for identification judgments.

PubMed

Fraser-Mackenzie, Peter A F; Dror, Itiel E; Wertheim, Kasey

2013-06-01

We examined forensic fingerprint examiners' suitability determinations of latent fingerprints comparing situations in which the latent is assessed solo (in isolation) versus situations in which it is presented alongside a comparison (matching or non-matching) exemplar print. The presence of a non-matching comparison exemplar led examiners to be more inclined to draw the conclusion that the latent was suitable for comparison compared to when the latent was presented solo. This effect persisted even when the latent presented was highly unsuitable for comparison. The presence of a matching comparison exemplar led examiners to be less likely to decide that the latent was suitable and more likely to decide the latent was questionable compared to solo analysis. This effect persisted even when the latent presented was highly suitable, suggesting a strong main effect. Knowledge of another examiner's previous determination that the latent was unsuitable was found to increase the likelihood that the examiner would conclude that the latent was unsuitable. However, knowledge of a previous "suitable" determination by another examiner did not increase the likelihood of a "suitable" conclusion by examiners. The finding that effects were weaker, although not entirely removed, in those with IAI certification suggests that training may be an appropriate route for reducing the effect of contextual influence and bias in suitability determinations. It was also shown that latent prints that were previously classed as "unsuitable" in a non-biasing context, continued to be judged to be "unsuitable" in a strongly biasing context (a major case in which a previous examiner was purported to have made an Individualization). Copyright © 2013 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Using latent class analysis to identify academic and behavioral risk status in elementary students.

PubMed

King, Kathleen R; Lembke, Erica S; Reinke, Wendy M

2016-03-01

Identifying classes of children on the basis of academic and behavior risk may have important implications for the allocation of intervention resources within Response to Intervention (RTI) and Multi-Tiered System of Support (MTSS) models. Latent class analysis (LCA) was conducted with a sample of 517 third grade students. Fall screening scores in the areas of reading, mathematics, and behavior were used as indicators of success on an end of year statewide achievement test. Results identified 3 subclasses of children, including a class with minimal academic and behavioral concerns (Tier 1; 32% of the sample), a class at-risk for academic problems and somewhat at-risk for behavior problems (Tier 2; 37% of the sample), and a class with significant academic and behavior problems (Tier 3; 31%). Each class was predictive of end of year performance on the statewide achievement test, with the Tier 1 class performing significantly higher on the test than the Tier 2 class, which in turn scored significantly higher than the Tier 3 class. The results of this study indicated that distinct classes of children can be determined through brief screening measures and are predictive of later academic success. Further implications are discussed for prevention and intervention for students at risk for academic failure and behavior problems. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Bark beetle-induced tree mortality alters stand energy budgets due to water budget changes

NASA Astrophysics Data System (ADS)

Reed, David E.; Ewers, Brent E.; Pendall, Elise; Frank, John; Kelly, Robert

2018-01-01

Insect outbreaks are major disturbances that affect a land area similar to that of forest fires across North America. The recent mountain pine bark beetle ( D endroctonus ponderosae) outbreak and its associated blue stain fungi ( Grosmannia clavigera) are impacting water partitioning processes of forests in the Rocky Mountain region as the spatially heterogeneous disturbance spreads across the landscape. Water cycling may dramatically change due to increasing spatial heterogeneity from uneven mortality. Water and energy storage within trees and soils may also decrease, due to hydraulic failure and mortality caused by blue stain fungi followed by shifts in the water budget. This forest disturbance was unique in comparison to fire or timber harvesting because water fluxes were altered before significant structural change occurred to the canopy. We investigated the impacts of bark beetles on lodgepole pine ( Pinus contorta) stand and ecosystem level hydrologic processes and the resulting vertical and horizontal spatial variability in energy storage. Bark beetle-impacted stands had on average 57 % higher soil moisture, 1.5 °C higher soil temperature, and 0.8 °C higher tree bole temperature over four growing seasons compared to unimpacted stands. Seasonal latent heat flux was highly correlated with soil moisture. Thus, high mortality levels led to an increase in ecosystem level Bowen ratio as sensible heat fluxes increased yearly and latent heat fluxes varied with soil moisture levels. Decline in canopy biomass (leaf, stem, and branch) was not seen, but ground-to-atmosphere longwave radiation flux increased, as the ground surface was a larger component of the longwave radiation. Variability in soil, latent, and sensible heat flux and radiation measurements increased during the disturbance. Accounting for stand level variability in water and energy fluxes will provide a method to quantify potential drivers of ecosystem processes and services as well as lead to greater confidence in measurements for all dynamic disturbances.

Multimethod latent class analysis

PubMed Central

Nussbeck, Fridtjof W.; Eid, Michael

2015-01-01

Correct and, hence, valid classifications of individuals are of high importance in the social sciences as these classifications are the basis for diagnoses and/or the assignment to a treatment. The via regia to inspect the validity of psychological ratings is the multitrait-multimethod (MTMM) approach. First, a latent variable model for the analysis of rater agreement (latent rater agreement model) will be presented that allows for the analysis of convergent validity between different measurement approaches (e.g., raters). Models of rater agreement are transferred to the level of latent variables. Second, the latent rater agreement model will be extended to a more informative MTMM latent class model. This model allows for estimating (i) the convergence of ratings, (ii) method biases in terms of differential latent distributions of raters and differential associations of categorizations within raters (specific rater bias), and (iii) the distinguishability of categories indicating if categories are satisfyingly distinct from each other. Finally, an empirical application is presented to exemplify the interpretation of the MTMM latent class model. PMID:26441714

Epidemiological trends and the effect of airport fever screening on prevention of domestic dengue fever outbreaks in Taiwan, 1998-2007.

PubMed

Kuan, Mei-Mei; Lin, Ting; Chuang, Jen-Hsiang; Wu, Ho-Sheng

2010-08-01

This study aimed to examine the epidemiological trends in dengue infection and the impact of imported cases and airport fever screening on community transmission in Taiwan, a dengue non-endemic island. All of the dengue case data were obtained from the surveillance system of the Taiwan Center for Disease Control and were analyzed by Pearson correlations, linear regression, and geographical information system (GIS)-based mapping. The impact of implementing airport fever screening was evaluated using the Student's t-test and two-way analysis of variance. A total of 10 351 dengue cases, including 7.1% of imported cases were investigated between 1998 and 2007. The majority of indigenous dengue cases (98.5%) were significantly clustered in southern Taiwan; 62.9% occurred in the metropolitan areas. The seasonality of dengue cases showed a peak from September to November. Airport fever screening was successful in identifying 45% (244/542 ; 95% confidence interval 33.1-57.8%) of imported dengue cases with fever. However, no statistical difference was found regarding the impact on community transmission when comparing the presence and absence of airport fever screening. Our results show that airport fever screening had a positive effect on partially blocking the local transmission of imported dengue cases, while those undetected cases due to latent or asymptomatic infection would be the source of new dengue outbreaks each year. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy.

PubMed

Lupia, E; Elliot, S J; Lenz, O; Zheng, F; Hattori, M; Striker, G E; Striker, L J

1999-08-01

Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

Do EBV Encoded Small RNAs Interfere with Tumor Suppressor APC in EBV Associated Breast Cancers

DTIC Science & Technology

2006-08-01

acute infectious mononucleosis but ultimately establishes persistent lifetime latent infection. In all latently infected cells EBVexpresses two small non...human initially causes acute infectious mononucleosis and later establishes persistent lifetime latent infection. In all latently EBV-infected cells, only

Bayesian Semiparametric Structural Equation Models with Latent Variables

ERIC Educational Resources Information Center

Yang, Mingan; Dunson, David B.

2010-01-01

Structural equation models (SEMs) with latent variables are widely useful for sparse covariance structure modeling and for inferring relationships among latent variables. Bayesian SEMs are appealing in allowing for the incorporation of prior information and in providing exact posterior distributions of unknowns, including the latent variables. In…

Unmanned Aircraft Systems Sensors

DTIC Science & Technology

2005-05-01

to development of UAS and UA sensor capabilities UNCLASSIFIED Small UA EO/IR Sensors • EO – Requirement for a facial recognition capability while...UNCLASSIFIED Tactical UA EO/IR Sensors • EO – Requirement for a facial recognition capability while remaining undetected. (NIIRS 8+) • IR – Requirement for...Operational & Theater UA EO/IR Sensors • EO – Requirement for a facial recognition capability while remaining undetected. (NIIRS 8+) • IR – Requirement

A Note on Cluster Effects in Latent Class Analysis

ERIC Educational Resources Information Center

Kaplan, David; Keller, Bryan

2011-01-01

This article examines the effects of clustering in latent class analysis. A comprehensive simulation study is conducted, which begins by specifying a true multilevel latent class model with varying within- and between-cluster sample sizes, varying latent class proportions, and varying intraclass correlations. These models are then estimated under…

Stochastic Approximation Methods for Latent Regression Item Response Models

ERIC Educational Resources Information Center

von Davier, Matthias; Sinharay, Sandip

2010-01-01

This article presents an application of a stochastic approximation expectation maximization (EM) algorithm using a Metropolis-Hastings (MH) sampler to estimate the parameters of an item response latent regression model. Latent regression item response models are extensions of item response theory (IRT) to a latent variable model with covariates…

Estimation and Model Selection for Finite Mixtures of Latent Interaction Models

ERIC Educational Resources Information Center

Hsu, Jui-Chen

2011-01-01

Latent interaction models and mixture models have received considerable attention in social science research recently, but little is known about how to handle if unobserved population heterogeneity exists in the endogenous latent variables of the nonlinear structural equation models. The current study estimates a mixture of latent interaction…

Bayesian Adaptive Lasso for Ordinal Regression with Latent Variables

ERIC Educational Resources Information Center

Feng, Xiang-Nan; Wu, Hao-Tian; Song, Xin-Yuan

2017-01-01

We consider an ordinal regression model with latent variables to investigate the effects of observable and latent explanatory variables on the ordinal responses of interest. Each latent variable is characterized by correlated observed variables through a confirmatory factor analysis model. We develop a Bayesian adaptive lasso procedure to conduct…

Depression and Delinquency Covariation in an Accelerated Longitudinal Sample of Adolescents

PubMed Central

Kofler, Michael J.; McCart, Michael R.; Zajac, Kristyn; Ruggiero, Kenneth J.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2015-01-01

Objectives The current study tested opposing predictions stemming from the failure and acting out theories of depression-delinquency covariation. Methods Participants included a nationwide longitudinal sample of adolescents (N = 3,604) ages 12 to 17. Competing models were tested using cohort-sequential latent growth curve modeling to determine whether depressive symptoms at age 12 (baseline) predicted concurrent and age-related changes in delinquent behavior, whether the opposite pattern was apparent (delinquency predicting depression), and whether initial levels of depression predict changes in delinquency significantly better than vice versa. Results Early depressive symptoms predicted age-related changes in delinquent behavior significantly better than early delinquency predicted changes in depressive symptoms. In addition, the impact of gender on age-related changes in delinquent symptoms was mediated by gender differences in depressive symptom changes, indicating that depressive symptoms are a particularly salient risk factor for delinquent behavior in girls. Conclusion Early depressive symptoms represent a significant risk factor for later delinquent behavior – especially for girls – and appear to be a better predictor of later delinquency than early delinquency is of later depression. These findings provide support for the acting out theory and contradict failure theory predictions. PMID:21787049

Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir

PubMed Central

Marshall, Jason D.; Dorwart, Michael R.; Heeke, Darren S.; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H.; Eisenberg, Roselyn J.

2017-01-01

ABSTRACT Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo. In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection. PMID:28228587

Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

PubMed

Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

2017-05-01

Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection. Copyright © 2017 American Society for Microbiology.

Sensitivity Analysis of the Land Surface Model NOAH-MP for Different Model Fluxes

NASA Astrophysics Data System (ADS)

Mai, Juliane; Thober, Stephan; Samaniego, Luis; Branch, Oliver; Wulfmeyer, Volker; Clark, Martyn; Attinger, Sabine; Kumar, Rohini; Cuntz, Matthias

2015-04-01

Land Surface Models (LSMs) use a plenitude of process descriptions to represent the carbon, energy and water cycles. They are highly complex and computationally expensive. Practitioners, however, are often only interested in specific outputs of the model such as latent heat or surface runoff. In model applications like parameter estimation, the most important parameters are then chosen by experience or expert knowledge. Hydrologists interested in surface runoff therefore chose mostly soil parameters while biogeochemists interested in carbon fluxes focus on vegetation parameters. However, this might lead to the omission of parameters that are important, for example, through strong interactions with the parameters chosen. It also happens during model development that some process descriptions contain fixed values, which are supposedly unimportant parameters. However, these hidden parameters remain normally undetected although they might be highly relevant during model calibration. Sensitivity analyses are used to identify informative model parameters for a specific model output. Standard methods for sensitivity analysis such as Sobol indexes require large amounts of model evaluations, specifically in case of many model parameters. We hence propose to first use a recently developed inexpensive sequential screening method based on Elementary Effects that has proven to identify the relevant informative parameters. This reduces the number parameters and therefore model evaluations for subsequent analyses such as sensitivity analysis or model calibration. In this study, we quantify parametric sensitivities of the land surface model NOAH-MP that is a state-of-the-art LSM and used at regional scale as the land surface scheme of the atmospheric Weather Research and Forecasting Model (WRF). NOAH-MP contains multiple process parameterizations yielding a considerable amount of parameters (˜ 100). Sensitivities for the three model outputs (a) surface runoff, (b) soil drainage and (c) latent heat are calculated on twelve Model Parameter Estimation Experiment (MOPEX) catchments ranging in size from 1020 to 4421 km2. This allows investigation of parametric sensitivities for distinct hydro-climatic characteristics, emphasizing different land-surface processes. The sequential screening identifies the most informative parameters of NOAH-MP for different model output variables. The number of parameters is reduced substantially for all of the three model outputs to approximately 25. The subsequent Sobol method quantifies the sensitivities of these informative parameters. The study demonstrates the existence of sensitive, important parameters in almost all parts of the model irrespective of the considered output. Soil parameters, e.g., are informative for all three output variables whereas plant parameters are not only informative for latent heat but also for soil drainage because soil drainage is strongly coupled to transpiration through the soil water balance. These results contrast to the choice of only soil parameters in hydrological studies and only plant parameters in biogeochemical ones. The sequential screening identified several important hidden parameters that carry large sensitivities and have hence to be included during model calibration.

Development of a high temperature storage unit for integration with solar dynamic systems

NASA Astrophysics Data System (ADS)

Staehle, H. J.; Lindner, F.

1989-08-01

Lithium fluoride in its capacity as a suitable energy storage material is investigated. Energy is stored as latent heat by melting the LiF. The energy is later released during recrystallization of the salt. Drawbacks to this system are described. The high corrosivity in molten state may lead to container failure in long term use. In order to avoid destruction of canisters, a graphite container is developed as graphite is not wetted by liquid LiF and thus does not suffer any corrosion. In order to match the mechanical forces caused by the volume increase during melting, a channel-like internal structure is tested. The melt formed first can expand into these channels and no pressure is built up. The results of these tests are presented.

Recruitment of Hexagenia mayfly nymphs in western Lake Erie linked to environmental variability

USGS Publications Warehouse

Bridgeman, Thomas B.; Schloesser, Don W.; Krause, Ann E.

2006-01-01

After a 40-year absence caused by pollution and eutrophication, burrowing mayflies (Hexagenia spp.) recolonized western Lake Erie in the mid 1990s as water quality improved. Mayflies are an important food resource for the economically valuable yellow perch fishery and are considered to be major indicator species of the ecological condition of the lake. Since their reappearance, however, mayfly populations have suffered occasional unexplained recruitment failures. In 2002, a failure of fall recruitment followed an unusually warm summer in which western Lake Erie became temporarily stratified, resulting in low dissolved oxygen levels near the lake floor. In the present study, we examined a possible link between Hexagenia recruitment and periods of intermittent stratification for the years 1997-2002. A simple model was developed using surface temperature, wind speed, and water column data from 2003 to predict stratification. The model was then used to detect episodes of stratification in past years for which water column data are unavailable. Low or undetectable mayfly recruitment occurred in 1997 and 2002, years in which there was frequent or extended stratification between June and September. Highest mayfly reproduction in 2000 corresponded to the fewest stratified periods. These results suggest that even relatively brief periods of stratification can result in loss of larval mayfly recruitment, probably through the effects of hypoxia. A trend toward increasing frequency of hot summers in the Great Lakes region could result in recurrent loss of mayfly larvae in western Lake Erie and other shallow areas in the Great Lakes.

The artful dodger: answering the wrong question the right way.

PubMed

Rogers, Todd; Norton, Michael I

2011-06-01

What happens when speakers try to "dodge" a question they would rather not answer by answering a different question? In 4 studies, we show that listeners can fail to detect dodges when speakers answer similar-but objectively incorrect-questions (the "artful dodge"), a detection failure that goes hand-in-hand with a failure to rate dodgers more negatively. We propose that dodges go undetected because listeners' attention is not usually directed toward a goal of dodge detection (i.e., Is this person answering the question?) but rather toward a goal of social evaluation (i.e., Do I like this person?). Listeners were not blind to all dodge attempts, however. Dodge detection increased when listeners' attention was diverted from social goals toward determining the relevance of the speaker's answers (Study 1), when speakers answered a question egregiously dissimilar to the one asked (Study 2), and when listeners' attention was directed to the question asked by keeping it visible during speakers' answers (Study 4). We also examined the interpersonal consequences of dodge attempts: When listeners were guided to detect dodges, they rated speakers more negatively (Study 2), and listeners rated speakers who answered a similar question in a fluent manner more positively than speakers who answered the actual question but disfluently (Study 3). These results add to the literatures on both Gricean conversational norms and goal-directed attention. We discuss the practical implications of our findings in the contexts of interpersonal communication and public debates.

Delamination Assessment Tool for Spacecraft Composite Structures

NASA Astrophysics Data System (ADS)

Portela, Pedro; Preller, Fabian; Wittke, Henrik; Sinnema, Gerben; Camanho, Pedro; Turon, Albert

2012-07-01

Fortunately only few cases are known where failure of spacecraft structures due to undetected damage has resulted in a loss of spacecraft and launcher mission. However, several problems related to damage tolerance and in particular delamination of composite materials have been encountered during structure development of various ESA projects and qualification testing. To avoid such costly failures during development, launch or service of spacecraft, launcher and reusable launch vehicles structures a comprehensive damage tolerance verification approach is needed. In 2009, the European Space Agency (ESA) initiated an activity called “Delamination Assessment Tool” which is led by the Portuguese company HPS Lda and includes academic and industrial partners. The goal of this study is the development of a comprehensive damage tolerance verification approach for launcher and reusable launch vehicles (RLV) structures, addressing analytical and numerical methodologies, material-, subcomponent- and component testing, as well as non-destructive inspection. The study includes a comprehensive review of current industrial damage tolerance practice resulting from ECSS and NASA standards, the development of new Best Practice Guidelines for analysis, test and inspection methods and the validation of these with a real industrial case study. The paper describes the main findings of this activity so far and presents a first iteration of a Damage Tolerance Verification Approach, which includes the introduction of novel analytical and numerical tools at an industrial level. This new approach is being put to the test using real industrial case studies provided by the industrial partners, MT Aerospace, RUAG Space and INVENT GmbH

Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells

PubMed Central

Aubé, Michel; Lafrance, Matthieu; Brodeur, Isabelle; Delisle, Marie-Chantal; Carreau, Madeleine

2003-01-01

Background Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. Methods Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. Results We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34- stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. Conclusions These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+ cells correlates with a role at the CD34+ differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism. PMID:12809565

Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report.

PubMed

Venkatesh, Prashanth; Shaikh, Nissar; Malmstrom, Mohammad F; Kumar, Vajjala R; Nour, Bakr

2014-08-25

Acute portomesenteric vein thrombosis is an uncommon but serious condition with potential sequelae, such as small-bowel gangrene and end-stage hepatic failure. It is known to be caused by various pro-thrombotic states, including hyperhomocysteinemia. We describe what is, to the best of our knowledge, the first reported case of concomitant thrombosis of portal, superior mesenteric and splenic veins due to hyperhomocysteinemia secondary to pernicious anemia and no other risk factors. A 60-year-old Indian man presented with epigastric pain, diarrhea and vomiting. An abdominal imaging scan showed that he had concomitant pernicious anemia and concomitant portal, superior mesenteric and splenic vein thrombosis. A work-up for the patient's hypercoagulable state revealed hyperhomocysteinemia, an undetectable vitamin B12 level and pernicious anemia with no other thrombophilic state. He developed infarction with perforation of the small bowel and subsequent septic shock with multi-organ dysfunction syndrome, and he ultimately died due to progressive hepatic failure. This report demonstrates that pernicious anemia, on its own, can lead to hyperhomocysteinemia significant enough to lead to lethal multiple splanchnic vein thrombosis. Our case also underscores the need to (1) consider portomesenteric thrombosis in the differential diagnosis of epigastric abdominal pain, (2) perform a complete thrombotic work-up to elucidate metabolic abnormalities that could be contributing to a pro-thrombotic state and (3) initiate aggressive measures, including early consideration of multi-visceral transplantation, in order to avoid decompensation and a significant adverse outcome.

Epstein–Barr virus latent genes

PubMed Central

Kang, Myung-Soo; Kieff, Elliott

2015-01-01

Latent Epstein–Barr virus (EBV) infection has a substantial role in causing many human disorders. The persistence of these viral genomes in all malignant cells, yet with the expression of limited latent genes, is consistent with the notion that EBV latent genes are important for malignant cell growth. While the EBV-encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are individually essential for in vitro transformation of primary B cells to lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this review, the roles of EBV latent genes are summarized. PMID:25613728

Photoinactivation of Latent Herpes Simplex Virus in Rabbit Kidney Cells

PubMed Central

Kelleher, J. J.; Varani, J.

1976-01-01

The photoinactivation of actively and nonactively growing herpes simplex virus by neutral red and proflavine was studied in rabbit kidney cells. Active virus growth was inhibited by both dyes under conditions which did not destroy the cells. Neutral red caused a much greater inhibition than proflavine. Neutral red also caused a reduction in the reactivation rate of latent virus when the infected cells were treated during the latent period. In the treated cultures that did reactivate virus, the average length of the latent period was increased over the control value. Proflavine treatment did not reduce the rate of reactivation of latent virus and did not increase the average latent period of the treated cultures. PMID:185948

Testing and Failure Mechanisms of Ice Phase Change Material Heat Exchangers

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Stephan, Ryan A.; Hawkins-Reynolds, Ebony

2010-01-01

Phase change materials (PCM) may be useful for thermal control systems that involve cyclical heat loads or cyclical thermal environments such as Low Earth Orbit (LEO) and Low Lunar Orbit (LLO). Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. One advantage that PCM s have over evaporators in this scenario is that they do not use a consumable. The use of water as a PCM rather than the more traditional paraffin wax has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. A number of ice PCM heat exchangers were fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion were investigated. This paper presents the results of testing that occurred from March through September of 2010 and builds on testing that occurred during the previous year.

Testing and Failure Mechanisms of Ice Phase Change Material Heat Exchangers

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Stephan, Ryan A.; Hawkins-Reynolds, Ebony

2011-01-01

Phase change materials (PCM) may be useful for thermal control systems that involve cyclical heat loads or cyclical thermal environments such as specific spacecraft orientations in Low Earth Orbit (LEO) and low beta angle Low Lunar Orbit (LLO). Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. One advantage that PCM s have over evaporators in this scenario is that they do not use a consumable. The use of water as a PCM rather than the more traditional paraffin wax has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. A number of ice PCM heat exchangers were fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion were investigated. This paper presents the results of testing that occurred from March through September of 2010 and builds on testing that occurred during the previous year.

The Integration of Continuous and Discrete Latent Variable Models: Potential Problems and Promising Opportunities

ERIC Educational Resources Information Center

Bauer, Daniel J.; Curran, Patrick J.

2004-01-01

Structural equation mixture modeling (SEMM) integrates continuous and discrete latent variable models. Drawing on prior research on the relationships between continuous and discrete latent variable models, the authors identify 3 conditions that may lead to the estimation of spurious latent classes in SEMM: misspecification of the structural model,…

Examining Factor Score Distributions to Determine the Nature of Latent Spaces

ERIC Educational Resources Information Center

Steinley, Douglas; McDonald, Roderick P.

2007-01-01

Similarities between latent class models with K classes and linear factor models with K-1 factors are investigated. Specifically, the mathematical equivalence between the covariance structure of the two models is discussed, and a Monte Carlo simulation is performed using generated data that represents both latent factors and latent classes with…

When do latent class models overstate accuracy for diagnostic and other classifiers in the absence of a gold standard?

PubMed

Spencer, Bruce D

2012-06-01

Latent class models are increasingly used to assess the accuracy of medical diagnostic tests and other classifications when no gold standard is available and the true state is unknown. When the latent class is treated as the true class, the latent class models provide measures of components of accuracy including specificity and sensitivity and their complements, type I and type II error rates. The error rates according to the latent class model differ from the true error rates, however, and empirical comparisons with a gold standard suggest the true error rates often are larger. We investigate conditions under which the true type I and type II error rates are larger than those provided by the latent class models. Results from Uebersax (1988, Psychological Bulletin 104, 405-416) are extended to accommodate random effects and covariates affecting the responses. The results are important for interpreting the results of latent class analyses. An error decomposition is presented that incorporates an error component from invalidity of the latent class model. © 2011, The International Biometric Society.

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment.

PubMed

Elvstam, Olof; Medstrand, Patrik; Yilmaz, Aylin; Isberg, Per-Erik; Gisslén, Magnus; Björkman, Per

2017-01-01

Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART. HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner. LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09). In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques

PubMed Central

Lin, Philana Ling; Dartois, Veronique; Johnston, Paul J.; Janssen, Christopher; Via, Laura; Goodwin, Michael B.; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

2012-01-01

Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB. PMID:22826237

Study on Latent Heat of Fusion of Ice in Aqueous Solutions

NASA Astrophysics Data System (ADS)

Kumano, Hiroyuki; Asaoka, Tatsunori; Saito, Akio; Okawa, Seiji

In this study, latent heat of fusion of ice in aqueous solutions was measured to understand latent heat of fusion of ice slurries. Propylene glycol, ethylene glycol, ethanol, NaCl and NaNO3 solutions were examined as the aqueous solutions. In the measurement, pure ice was put into the solution, and the temperature variation of the solution due to the melting of the ice was measured. Then, the effective latent heat of fusion was calculated from energy balance equation. When ice melts in solution, the concentration of the solution varies due to the melting of the ice, and dilution heat must be considered. Therefore, the latent heat of fusion of ice in aqueous solutions was predicted by considering the effects of dilution and freezing-point depression. The latent heat of fusion was also measured by differential scanning calorimetry(DSC) to compare the results obtained from the experiments with that obtained by DSC. As the result, it was found that the effective latent heat of fusion of ice decreased with the increase of the concentration of solution, and the effective latent heat of fusion was calculated from latent heat of fusion of pure ice and the effects of freezing-point depression and the dilution heat.

The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons

PubMed Central

Nicoll, Michael P.; Hann, William; Shivkumar, Maitreyi; Harman, Laura E. R.; Connor, Viv; Coleman, Heather M.; Proença, João T.; Efstathiou, Stacey

2016-01-01

Herpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir. PMID:27055281

HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

PubMed

Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

2013-10-24

The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus replication. HIV infected TOM undergoing ART harbor latently infected, resting CD4+ T cells.

Latent Heating from TRMM Satellite Measurements

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Smith, E. A.; Adler, R.; Haddad, Z.; Hou, A.; Iguchi, T.; Kakar, R.; Krishnamurti, T.; Kummerow, C.; Lang, S.

2004-01-01

Rainfall production is the fundamental variable within the Earth's hydrological cycle because it is both the principal forcing term in surface water budgets and its energetics corollary, latent heating, is the principal source of atmospheric diabatic heating. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water. The properties of the vertical distribution of latent heat release modulate large-scale meridional and zonal circulations within the tropics - as well as modifying the energetic efficiencies of midlatitude weather systems. This paper focuses on the retrieval of latent heat release from satellite measurements generated by the Tropical Rainfall Measuring Mission (TRMM) satellite observatory, which was launched in November 1997 as a joint American-Japanese space endeavor. Since then, TRMM measurements have been providing an accurate four-dimensional account of rainfall over the global tropics and sub-tropics, information which can be used to estimate the space-time structure of latent heating across the Earth's low latitudes. The paper examines how the observed TRMM distribution of rainfall has advanced an understanding of the global water and energy cycle and its consequent relationship to the atmospheric general circulation and climate via latent heat release. A set of algorithm methodologies that are being used to estimate latent heating based on rain rate retrievals from the TRMM observations are described. The characteristics of these algorithms and the latent heating products that can be generated from them are also described, along with validation analyses of the heating products themselves. Finally, the investigation provides an overview of how TRMM-derived latent heating information is currently being used in conjunction with global weather and climate models, concluding with remarks intended to stimulate further research on latent heating retrieval from satellites.

Poor Government Oversight of Anham and Its Subcontracting Procedures Allowed Questionable Costs To Go Undetected

DTIC Science & Technology

2011-07-30

contractor purchasing system review of Anham. Management Comments and Audit Response The Defense Contract Mangement Agency and the U.S. Central... Introduction 1  Background 1  Government Agency Roles and Oversight Responsibilities 4  Objectives 7  Weak Government Oversight Resulted in Significant...Subcontracting Procedures Allowed Questionable Costs To Go Undetected SIGIR 11-022 July 30, 2011 Introduction Since 2003, the United States Government

Probability of undetected error after decoding for a concatenated coding scheme

NASA Technical Reports Server (NTRS)

Costello, D. J., Jr.; Lin, S.

1984-01-01

A concatenated coding scheme for error control in data communications is analyzed. In this scheme, the inner code is used for both error correction and detection, however the outer code is used only for error detection. A retransmission is requested if the outer code detects the presence of errors after the inner code decoding. Probability of undetected error is derived and bounded. A particular example, proposed for NASA telecommand system is analyzed.

A frameshift mutation in GON4L is associated with proportionate dwarfism in Fleckvieh cattle.

PubMed

Schwarzenbacher, Hermann; Wurmser, Christine; Flisikowski, Krzysztof; Misurova, Lubica; Jung, Simone; Langenmayer, Martin C; Schnieke, Angelika; Knubben-Schweizer, Gabriela; Fries, Ruedi; Pausch, Hubert

2016-03-31

Low birth weight and postnatal growth restriction are the most evident symptoms of dwarfism. Accompanying skeletal aberrations may compromise the general condition and locomotion of affected individuals. Several paternal half-sibs with a low birth weight and a small size were born in 2013 in the Fleckvieh cattle population. Affected calves were strikingly underweight at birth in spite of a normal gestation length and had craniofacial abnormalities such as elongated narrow heads and brachygnathia inferior. In spite of a normal general condition, their growth remained restricted during rearing. We genotyped 27 affected and 10,454 unaffected animals at 44,672 single nucleotide polymorphisms and performed association tests followed by homozygosity mapping, which allowed us to map the locus responsible for growth failure to a 1.85-Mb segment on bovine chromosome 3. Analysis of whole-genome re-sequencing data from one affected and 289 unaffected animals revealed a 1-bp deletion (g.15079217delC, rs723240647) in the coding region of the GON4L gene that segregated with the dwarfism-associated haplotype. We showed that the deletion induces intron retention and premature termination of translation, which can lead to a severely truncated protein that lacks domains that are likely essential to normal protein function. The widespread use of an undetected carrier bull for artificial insemination has resulted in a tenfold increase in the frequency of the deleterious allele in the female population. A frameshift mutation in GON4L is associated with autosomal recessive proportionate dwarfism in Fleckvieh cattle. The mutation has segregated in the population for more than 50 years without being recognized as a genetic disorder. However, the widespread use of an undetected carrier bull for artificial insemination caused a sudden accumulation of homozygous calves with dwarfism. Our findings provide the basis for genome-based mating strategies to avoid the inadvertent mating of carrier animals and thereby prevent the birth of homozygous calves with impaired growth.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

PubMed

Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

2017-06-01

In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Randomised Study to Assess the Efficacy and Safety of Once-Daily Etravirine-Based Regimen as a Switching Strategy in HIV-Infected Patients Receiving a Protease Inhibitor–Containing Regimen. Etraswitch Study

PubMed Central

Echeverría, Patricia; Bonjoch, Anna; Puig, Jordi; Moltó, José; Paredes, Roger; Sirera, Guillem; Ornelas, Arelly; Pérez-Álvarez, Nuria; Clotet, Bonaventura; Negredo, Eugènia

2014-01-01

Background Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking. Methods HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL≤50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile. Results We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25) and −4 cells/µL in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p<0.001), triglycerides (p = <0.001), and glycemia (p = 0.03) and higher satisfaction (0–10 scale) (p = 0.04). Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily. Conclusion Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly. Trial Registration ClinicalTrials.gov NCT01034917 PMID:24503952

The significance of HIV 'blips' in resource-limited settings: is it the same? analysis of the treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD).

PubMed

Kanapathipillai, Rupa; McManus, Hamish; Kamarulzaman, Adeeba; Lim, Poh Lian; Templeton, David J; Law, Matthew; Woolley, Ian

2014-01-01

Magnitude and frequency of HIV viral load blips in resource-limited settings, has not previously been assessed. This study was undertaken in a cohort from a high income country (Australia) known as AHOD (Australian HIV Observational Database) and another cohort from a mixture of Asian countries of varying national income per capita, TAHOD (TREAT Asia HIV Observational Database). Blips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed. 5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50-≤1000, p = 0.309 for blip 50-≤400 and p = 0.300 for blip 50-≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip. Despite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips.

Polytomous Latent Scales for the Investigation of the Ordering of Items

ERIC Educational Resources Information Center

Ligtvoet, Rudy; van der Ark, L. Andries; Bergsma, Wicher P.; Sijtsma, Klaas

2011-01-01

We propose three latent scales within the framework of nonparametric item response theory for polytomously scored items. Latent scales are models that imply an invariant item ordering, meaning that the order of the items is the same for each measurement value on the latent scale. This ordering property may be important in, for example,…

Latent-Trait Latent-Class Analysis of Self-Disclosure in the Work Environment

ERIC Educational Resources Information Center

Maij-de Meij, Annette M.; Kelderman, Henk; van der Flier, Henk

2005-01-01

Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of self-disclosure. The model was used to analyze the data…

Detecting Mixtures from Structural Model Differences Using Latent Variable Mixture Modeling: A Comparison of Relative Model Fit Statistics

ERIC Educational Resources Information Center

Henson, James M.; Reise, Steven P.; Kim, Kevin H.

2007-01-01

The accuracy of structural model parameter estimates in latent variable mixture modeling was explored with a 3 (sample size) [times] 3 (exogenous latent mean difference) [times] 3 (endogenous latent mean difference) [times] 3 (correlation between factors) [times] 3 (mixture proportions) factorial design. In addition, the efficacy of several…

Stochastic Approximation Methods for Latent Regression Item Response Models. Research Report. ETS RR-09-09

ERIC Educational Resources Information Center

von Davier, Matthias; Sinharay, Sandip

2009-01-01

This paper presents an application of a stochastic approximation EM-algorithm using a Metropolis-Hastings sampler to estimate the parameters of an item response latent regression model. Latent regression models are extensions of item response theory (IRT) to a 2-level latent variable model in which covariates serve as predictors of the…

A General Approach to Defining Latent Growth Components

ERIC Educational Resources Information Center

Mayer, Axel; Steyer, Rolf; Mueller, Horst

2012-01-01

We present a 3-step approach to defining latent growth components. In the first step, a measurement model with at least 2 indicators for each time point is formulated to identify measurement error variances and obtain latent variables that are purged from measurement error. In the second step, we use contrast matrices to define the latent growth…

Latent Curve Models and Latent Change Score Models Estimated in R

ERIC Educational Resources Information Center

Ghisletta, Paolo; McArdle, John J.

2012-01-01

In recent years the use of the latent curve model (LCM) among researchers in social sciences has increased noticeably, probably thanks to contemporary software developments and the availability of specialized literature. Extensions of the LCM, like the the latent change score model (LCSM), have also increased in popularity. At the same time, the R…

Mixture IRT Model with a Higher-Order Structure for Latent Traits

ERIC Educational Resources Information Center

Huang, Hung-Yu

2017-01-01

Mixture item response theory (IRT) models have been suggested as an efficient method of detecting the different response patterns derived from latent classes when developing a test. In testing situations, multiple latent traits measured by a battery of tests can exhibit a higher-order structure, and mixtures of latent classes may occur on…

Harry Potter and the sorcerer's scope: latent scope biases in explanatory reasoning.

PubMed

Khemlani, Sangeet S; Sussman, Abigail B; Oppenheimer, Daniel M

2011-04-01

What makes a good explanation? We examine the function of latent scope, i.e., the number of unobserved phenomena that an explanation can account for. We show that individuals prefer narrow latent scope explanations-those that account for fewer unobserved effects-to broader explanations. In Experiments 1a-d, participants found narrow latent scope explanations to be both more satisfying and more likely. In Experiment 2 we directly manipulated base rate information and again found a preference for narrow latent scope explanations. Participants in Experiment 3 evaluated more natural explanations of unexpected observations, and again displayed a bias for narrow latent scope explanations. We conclude by considering what this novel bias tells us about how humans evaluate explanations and engage in causal reasoning.

Health-related quality of life is not impaired in children with undetected as well as diagnosed celiac disease: a large population based cross-sectional study

PubMed Central

2014-01-01

Background Knowledge regarding the health-related quality of life (HRQoL) of children with celiac disease remains limited and inconclusive. We investigated the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii) clinically diagnosed celiac disease, and iii) without celiac disease. Methods A school-based cross-sectional multicenter screening study invited 18 325 children, whereof 68% consented to participate. Participants provided a blood sample, which was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were elevated, a small intestinal biopsy verified the screening-detected celiac disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52 items instrument with proven reliability and validity. Scores were linearly transformed into a 0–100 scale with higher values indicating better HRQoL. Mean values with standard deviations (mean ± SD) were compared, and uni- and multivariate logistic regression models tested the odds of a low HRQoL among children with undetected or diagnosed celiac disease, respectively. Results Children with undetected celiac disease (n = 238) reported similar HRQoL as children without celiac disease (n = 12 037) (83.0 ± 11.0 vs. 82.5 ± 11.3, P = 0.51), and also similar HRQoL (82.2 ± 12.2, P = 0.28) to that of children with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment. Having undetected celiac disease did not increase the odds of low overall HRQoL, independent of sex, area of residence, study year and occurrence of gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10). Comparable results were seen for diagnosed celiac disease cases (adjusted odds ratio 1.11, 95% CI 0.67-1.85). Conclusion Children with undetected celiac disease reported comparable HRQoL as their peers with diagnosed celiac disease, and those without celiac disease, when reporting prior to receiving the diagnosis through screening. Thus, children with celiac disease, both untreated and diagnosed, perceive their HRQoL as unimpaired by their disease. PMID:24884747

Latent Heating Structures Derived from TRMM

NASA Technical Reports Server (NTRS)

Tao, W.-K.; Smith, E. A.; Adler, R.; Hou, A.; Kakar, R.; Krishnamurti, T.; Kummerow, C.; Lang, S.; Olson, W.; Satoh, S.

2004-01-01

Rainfall is the fundamental variable within the Earth's hydrological cycle because it is both the main forcing term leading to variations in continental and oceanic surface water budgets. The vertical distribution of latent heat release, which is accompanied with rain, modulates large-scale meridional and zonal circulations within the tropics as well as modifying the energetic efficiency of mid-latitude weather systems. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water.This paper focuses on the retrieval of latent heat release from satellite measurements generated by the Tropical Rainfall Measuring Mission 0. The TRMM observatory, whose development was a joint US-Japan space endeavor, was launched in November 1997. TRMM measurements provide an accurate account of rainfall over the global tropics, information which can be .used to estimate the four-dimensional structure of latent heating across the entire tropical and sub-tropical regions. Various algorithm methodologies for estimating latent heating based on rain rate measurements from TRMM observations are described. The strengths and weaknesses of these algorithms, as well as the latent heating products generated by these algorithms, are also discussed along with validation analyses of the products. The investigation paper provides an overview of how TRMM-derived latent heating information is currently being used in conjunction with global weather and climate models, and concludes with remarks designed to stimulate further research on latent heating retrieval

Latent Heating from TRMM Satellite Measurements

NASA Technical Reports Server (NTRS)

Tao, W.-K.; Smith, E.; Olson, W.

2005-01-01

Rainfall production is a fundamental process within the Earth;s hydrological cycle because it represents both a principal forcing term in surface water budgets, and its energetics corollary, latent heating, is the principal source of atmospheric diabatic heating. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water. The properties of the vertical distribution of latent heat release modulate large-scale meridional and zonal circulations with the Tropics - as well as modify the energetic efficiencies of mid-latitude weather systems. This paper highlights the retrieval of observatory, which was launched in November 1997 as a joint American-Japanese space endeavor. Since then, TRMM measurements have been providing an accurate four-dimensional amount of rainfall over the global Tropics and sub-tropics - information which can be used to estimate the spacetime structure of latent heating across the Earth's low latitudes. A set of algorithm methodologies has and continues to be developed to estimate latent heating based on rain rate profile retrievals obtained from TRMM measurements. These algorithms are briefly described followed by a discussion of the foremost latent heating products that can be generate from them. The investigation then provides an overview of how TRMM-derived latent heating information is currently being used in conjunction with global weather and climate models, concluding with remarks intended to stimulate further research on latent heating retrieval from satellites.

Primiparous women's preferences for care during a prolonged latent phase of labour.

PubMed

Ängeby, Karin; Wilde-Larsson, Bodil; Hildingsson, Ingegerd; Sandin-Bojö, Ann-Kristin

2015-10-01

To investigate primiparous women's preferences for care during a prolonged latent phase of labour. A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. Copyright © 2015 Elsevier B.V. All rights reserved.

Release of active TGF-β1 from the latent TGF-β1/GARP complex on T regulatory cells is mediated by integrin β8.

PubMed

Edwards, Justin P; Thornton, Angela M; Shevach, Ethan M

2014-09-15

Activated T regulatory cells (Tregs) express latent TGF-β1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF-β1 from the complex of latent TGF-β1 and latent TGF-β1 binding protein, their role in processing latent TGF-β1 from the latent TGF-β1/GARP complex is unclear. Mouse CD4(+)Foxp3(+) Treg, but not CD4(+)Foxp3(-) T cells, expressed integrin β8 (Itgb8) as detected by quantitative RT-PCR. Itgb8 expression was a marker of thymically derived (t)Treg, because it could not be detected on Foxp3(+)Helios(-) Tregs or on Foxp3(+) T cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal suppressor function in vitro and in vivo in a model of colitis but failed to provide TGF-β1 to drive Th17 or induced Treg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-β1 on their cell surface consistent with defective processing. Thus, integrin αvβ8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF-β1 from the latent TGF-β1/GARP complex on the surface of tTregs.

Estimating Non-Normal Latent Trait Distributions within Item Response Theory Using True and Estimated Item Parameters

ERIC Educational Resources Information Center

Sass, D. A.; Schmitt, T. A.; Walker, C. M.

2008-01-01

Item response theory (IRT) procedures have been used extensively to study normal latent trait distributions and have been shown to perform well; however, less is known concerning the performance of IRT with non-normal latent trait distributions. This study investigated the degree of latent trait estimation error under normal and non-normal…

Exploring Latent Class Based on Growth Rates in Number Sense Ability

ERIC Educational Resources Information Center

Kim, Dongil; Shin, Jaehyun; Lee, Kijyung

2013-01-01

The purpose of this study was to explore latent class based on growth rates in number sense ability by using latent growth class modeling (LGCM). LGCM is one of the noteworthy methods for identifying growth patterns of the progress monitoring within the response to intervention framework in that it enables us to analyze latent sub-groups based not…

A Latent Variable Approach to the Simple View of Reading

ERIC Educational Resources Information Center

Kershaw, Sarah; Schatschneider, Chris

2012-01-01

The present study utilized a latent variable modeling approach to examine the Simple View of Reading in a sample of students from 3rd, 7th, and 10th grades (N = 215, 188, and 180, respectively). Latent interaction modeling and other latent variable models were employed to investigate (a) the functional form of the relationship between decoding and…

Exploring the Estimation of Examinee Locations Using Multidimensional Latent Trait Models under Different Distributional Assumptions

ERIC Educational Resources Information Center

Jang, Hyesuk

2014-01-01

This study aims to evaluate a multidimensional latent trait model to determine how well the model works in various empirical contexts. Contrary to the assumption of these latent trait models that the traits are normally distributed, situations in which the latent trait is not shaped with a normal distribution may occur (Sass et al, 2008; Woods…

The Impact of Ignoring the Level of Nesting Structure in Nonparametric Multilevel Latent Class Models

ERIC Educational Resources Information Center

Park, Jungkyu; Yu, Hsiu-Ting

2016-01-01

The multilevel latent class model (MLCM) is a multilevel extension of a latent class model (LCM) that is used to analyze nested structure data structure. The nonparametric version of an MLCM assumes a discrete latent variable at a higher-level nesting structure to account for the dependency among observations nested within a higher-level unit. In…

A Bayesian Model for the Estimation of Latent Interaction and Quadratic Effects When Latent Variables Are Non-Normally Distributed

ERIC Educational Resources Information Center

Kelava, Augustin; Nagengast, Benjamin

2012-01-01

Structural equation models with interaction and quadratic effects have become a standard tool for testing nonlinear hypotheses in the social sciences. Most of the current approaches assume normally distributed latent predictor variables. In this article, we present a Bayesian model for the estimation of latent nonlinear effects when the latent…

Defining a Family of Cognitive Diagnosis Models Using Log-Linear Models with Latent Variables

ERIC Educational Resources Information Center

Henson, Robert A.; Templin, Jonathan L.; Willse, John T.

2009-01-01

This paper uses log-linear models with latent variables (Hagenaars, in "Loglinear Models with Latent Variables," 1993) to define a family of cognitive diagnosis models. In doing so, the relationship between many common models is explicitly defined and discussed. In addition, because the log-linear model with latent variables is a general model for…

Behaviorism, Latent Learning, and Cognitive Maps: Needed Revisions in Introductory Psychology Textbooks

PubMed Central

Jensen, Robert

2006-01-01

This paper critically assesses the scholarship in introductory psychology textbooks in relation to the topic of latent learning. A review of the treatment of latent learning in 48 introductory psychology textbooks published between 1948 and 2004, with 21 of these texts published since 1999, reveals that the scholarship on the topic of latent learning demonstrated in introductory textbooks warrants improvement. Errors that persist in textbooks include the assertion that the latent learning experiments demonstrate unequivocally that reinforcement was not necessary for learning to occur, that behavioral theories could not account for the results of the latent learning experiments, that B. F. Skinner was an S-R association behaviorist who argued that reinforcement is necessary for learning to occur, and that because behavioral theories (including that of B. F. Skinner) were unable explain the results of the latent learning experiments the cognitive map invoked by Edward Tolman is the only explanation for latent learning. Finally, the validity of the cognitive map is typically accepted without question. Implications of the presence of these errors for students and the discipline are considered. Lastly, remedies are offered to improve the scholarship found in introductory psychology textbooks. PMID:22478463

Tropical Gravity Wave Momentum Fluxes and Latent Heating Distributions

NASA Technical Reports Server (NTRS)

Geller, Marvin A.; Zhou, Tiehan; Love, Peter T.

2015-01-01

Recent satellite determinations of global distributions of absolute gravity wave (GW) momentum fluxes in the lower stratosphere show maxima over the summer subtropical continents and little evidence of GW momentum fluxes associated with the intertropical convergence zone (ITCZ). This seems to be at odds with parameterizations forGWmomentum fluxes, where the source is a function of latent heating rates, which are largest in the region of the ITCZ in terms of monthly averages. The authors have examined global distributions of atmospheric latent heating, cloud-top-pressure altitudes, and lower-stratosphere absolute GW momentum fluxes and have found that monthly averages of the lower-stratosphere GW momentum fluxes more closely resemble the monthly mean cloud-top altitudes rather than the monthly mean rates of latent heating. These regions of highest cloud-top altitudes occur when rates of latent heating are largest on the time scale of cloud growth. This, plus previously published studies, suggests that convective sources for stratospheric GW momentum fluxes, being a function of the rate of latent heating, will require either a climate model to correctly model this rate of latent heating or some ad hoc adjustments to account for shortcomings in a climate model's land-sea differences in convective latent heating.

Semiparametric Time-to-Event Modeling in the Presence of a Latent Progression Event

PubMed Central

Rice, John D.; Tsodikov, Alex

2017-01-01

Summary In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood–based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set. PMID:27556886

Semiparametric time-to-event modeling in the presence of a latent progression event.

PubMed

Rice, John D; Tsodikov, Alex

2017-06-01

In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood-based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set. © 2016, The International Biometric Society.

Person Re-Identification via Distance Metric Learning With Latent Variables.

PubMed

Sun, Chong; Wang, Dong; Lu, Huchuan

2017-01-01

In this paper, we propose an effective person re-identification method with latent variables, which represents a pedestrian as the mixture of a holistic model and a number of flexible models. Three types of latent variables are introduced to model uncertain factors in the re-identification problem, including vertical misalignments, horizontal misalignments and leg posture variations. The distance between two pedestrians can be determined by minimizing a given distance function with respect to latent variables, and then be used to conduct the re-identification task. In addition, we develop a latent metric learning method for learning the effective metric matrix, which can be solved via an iterative manner: once latent information is specified, the metric matrix can be obtained based on some typical metric learning methods; with the computed metric matrix, the latent variables can be determined by searching the state space exhaustively. Finally, extensive experiments are conducted on seven databases to evaluate the proposed method. The experimental results demonstrate that our method achieves better performance than other competing algorithms.

Studies of Phase Change Materials and a Latent Heat Storage Unit Used for a Natural Circulation Cooling/Latent Heat Storage System

NASA Astrophysics Data System (ADS)

Sakitani, Katsumi; Honda, Hiroshi

Experiments were performed to investigate feasibility of using organic materials as a PCM for a latent heat storage unit of a natural circulation cooling/latent heat storage system. This system was designed to cool a shelter accommodating telecommunication equipment located in subtropical deserts or similar regions without using a power source. Taking into account practical considerations and the results of various experiments regarding the thermodynamic properties, thermal degradation, and corrosiveness to metals, lauric acid and iron was selected for the PCM and the latent heat storage unit material, respectively. Cyclic heating and cooling of the latent heat storage unit undergoing solid-liquid phase change was repeated for more than 430 days. The results showed that the heating-cooling curve was almost unchanged between the early stage and the 1,870th cycle. It was concluded that the latent heat storage unit could be used safely for more than ten years as a component of the cooling system.

HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood.

PubMed

Du, Peiwei; Liu, An; Jiao, Yanmei; Liu, Cuie; Jiang, Taiyi; Zhu, Weijun; Zhu, Yunxia; Wu, Hao; Sun, Lijun

2016-03-01

The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Development and Application of Methods for Estimating Operating Characteristics of Discrete Test Item Responses without Assuming any Mathematical Form.

ERIC Educational Resources Information Center

Samejima, Fumiko

In latent trait theory the latent space, or space of the hypothetical construct, is usually represented by some unidimensional or multi-dimensional continuum of real numbers. Like the latent space, the item response can either be treated as a discrete variable or as a continuous variable. Latent trait theory relates the item response to the latent…

Validation of Diagnostic Measures Based on Latent Class Analysis: A Step Forward in Response Bias Research

ERIC Educational Resources Information Center

Thomas, Michael L.; Lanyon, Richard I.; Millsap, Roger E.

2009-01-01

The use of criterion group validation is hindered by the difficulty of classifying individuals on latent constructs. Latent class analysis (LCA) is a method that can be used for determining the validity of scales meant to assess latent constructs without such a priori classifications. The authors used this method to examine the ability of the L…

Risk assessment to estimate the probability of a chicken flock infected with H5N1 highly pathogenic avian influenza virus reaching slaughter undetected.

PubMed

Golden, Neal J; Schlosser, Wayne D; Ebel, Eric D

2009-09-01

Highly pathogenic avian influenza (HPAI) H5N1 is an infectious disease of fowl that can cause rapid and pervasive mortality resulting in complete flock loss. It has also been shown to cause death in humans. Although H5N1 HPAI virus (HPAIV) has not been identified in the United States, there are concerns about whether an infected flock could remain undetected long enough to pose a risk to consumers. This paper considers exposure from an Asian lineage H5N1 HPAIV-infected chicken flock given that no other flocks have been identified as H5N1 HPAIV positive (the index flock). A state-transition model is used to evaluate the probability of an infected flock remaining undetected until slaughter. This model describes three possible states within the flock: susceptible, infected, and dead, and the transition probabilities that predict movements between the possible states. Assuming a 20,000-bird house with 1 bird initially infected, the probability that an H5N1 HPAIV-infected flock would be detected before slaughter is approximately 94%. This is because H5N1 HPAIV spreads rapidly through a flock, and bird mortality quickly reaches high levels. It is assumed that approximately 2% or greater bird mortality due to H5N1 HPAIV would result in on-farm identification of the flock as infected. The only infected flock likely to reach slaughter undetected is one that was infected within approximately 3.5 days of shipment. In this situation, there is not enough time for high mortality to present. These results suggest that the probability of an infected undetected flock going to slaughter is low, yet such an event could occur if a flock is infected at the most opportune time.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin.

PubMed

Rubini Giménez, Maria; Hoeller, Rebeca; Reichlin, Tobias; Zellweger, Christa; Twerenbold, Raphael; Reiter, Miriam; Moehring, Berit; Wildi, Karin; Mosimann, Tamina; Mueller, Mira; Meller, Bernadette; Hochgruber, Thomas; Ziller, Ronny; Sou, Seoung Mann; Murray, Karsten; Sakarikos, Konstantin; Ernst, Susanne; Gea, Joaquim; Campodarve, Isabel; Vilaplana, Carles; Haaf, Philip; Steuer, Stephan; Minners, Jan; Osswald, Stefan; Mueller, Christian

2013-10-09

We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays. © 2013.

Thoracoscopic anatomical lung segmentectomy using 3D computed tomography simulation without tumour markings for non-palpable and non-visualized small lung nodules.

PubMed

Kato, Hirohisa; Oizumi, Hiroyuki; Suzuki, Jun; Hamada, Akira; Watarai, Hikaru; Sadahiro, Mitsuaki

2017-09-01

Although wedge resection can be curative for small lung tumours, tumour marking is sometimes required for resection of non-palpable or visually undetectable lung nodules as a method for identification of tumours. Tumour marking sometimes fails and occasionally causes serious complications. We have performed many thoracoscopic segmentectomies using 3D computed tomography simulation for undetectable small lung tumours without any tumour markings. The aim of this study was to investigate whether thoracoscopic segmentectomy planned with 3D computed tomography simulation could precisely remove non-palpable and visually undetectable tumours. Between January 2012 and March 2016, 58 patients underwent thoracoscopic segmentectomy using 3D computed tomography simulation for non-palpable, visually undetectable tumours. Surgical outcomes were evaluated. A total of 35, 14 and 9 patients underwent segmentectomy, subsegmentectomy and segmentectomy combined with adjacent subsegmentectomy, respectively. All tumours were correctly resected without tumour marking. The median tumour size and distance from the visceral pleura was 14 ± 5.2 mm (range 5-27 mm) and 11.6 mm (range 1-38.8 mm), respectively. Median values related to the procedures were operative time, 176 min (range 83-370 min); blood loss, 43 ml (range 0-419 ml); duration of chest tube placement, 1 day (range 1-8 days); and postoperative hospital stay, 5 days (range 3-12 days). Two cases were converted to open thoracotomy due to bleeding. Three cases required pleurodesis for pleural fistula. No recurrences occurred during the mean follow-up period of 44.4 months (range 5-53 months). Thoracoscopic segmentectomy using 3D computed tomography simulation was feasible and could be performed to resect undetectable tumours with no tumour markings. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Aqueous Extracts of Hibiscus sabdariffa Calyces Decrease Hepatitis A Virus and Human Norovirus Surrogate Titers.

PubMed

Joshi, Snehal S; Dice, Lezlee; D'Souza, Doris H

2015-12-01

Hibiscus sabdariffa extract is known to have antioxidant, anti-diabetic, and antimicrobial properties. However, their effects against foodborne viruses are currently unknown. The objective of this study was to determine the antiviral effects of aqueous extracts of H. sabdariffa against human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and hepatitis A virus (HAV) at 37 °C over 24 h. Individual viruses (~5 log PFU/ml) were incubated with 40 or 100 mg/ml of aqueous hibiscus extract (HE; pH 3.6), protocatechuic acid (PCA; 3 or 6 mg/ml, pH 3.6), ferulic acid (FA; 0.5 or 1 mg/ml; pH 4.0), malic acid (10 mM; pH 3.0), or phosphate buffered saline (pH 7.2 as control) at 37 °C over 24 h. Each treatment was replicated thrice and plaque assayed in duplicate. FCV-F9 titers were reduced to undetectable levels after 15 min with both 40 and 100 mg/ml HE. MNV-1 was reduced by 1.77 ± 0.10 and 1.88 ± 0.12 log PFU/ml after 6 h with 40 and 100 mg/ml HE, respectively, and to undetectable levels after 24 h by both concentrations. HAV was reduced to undetectable levels by both HE concentrations after 24 h. PCA at 3 mg/ml reduced FCV-F9 titers to undetectable levels after 6 h, MNV-1 by 0.53 ± 0.01 log PFU/ml after 6 h, and caused no significant change in HAV titers. FA reduced FCV-F9 to undetectable levels after 3 h and MNV-1 and HAV after 24 h. Transmission electron microscopy showed no conclusive results. The findings suggest that H. sabdariffa extracts have potential to prevent foodborne viral transmission.

Experimental study on latent heat storage characteristics of W/O emulsion -Supercooling rate of dispersed water drops by direct contact heat exchange-

NASA Astrophysics Data System (ADS)

Morita, Shin-ichi; Hayamizu, Yasutaka; Horibe, Akihiko; Haruki, Naoto; Inaba, Hideo

2013-04-01

Recently, much attention has been paid to investigate the latent heat storage system. Using of ice heat storage system brings an equalization of electric power demand, because it will solved the electric -power-demand-concentration on day-time of summer by the air conditioning. The flowable latent heat storage material, Oil/Water type emulsion, microencapsulated latent heat material-water mixture or ice slurry, etc., is enable to transport the latent heat in a pipe. The flowable latent heat storage material can realize the pipe size reduction and system efficiency improvement. Supercooling phenomenon of the dispersed latent heat storage material in continuous phase brings the obstruction of latent heat storage. The latent heat storage rates of dispersed water drops in W/O (Water/Oil) emulsion are investigated experimentally in this study. The water drops in emulsion has the diameter within 3 ˜ 25μm, the averaged water drop diameter is 7.3μm and the standard deviation is 2.9μm. The direct contact heat exchange method is chosen as the phase change rate evaluation of water drops in W/O emulsion. The supercooled temperature and the cooling rate are set as parameters of this study. The evaluation is performed by comparison between the results of this study and the past research. The obtained experimental result is shown that the 35K or more degree from melting point brings 100% latent heat storage rate of W/O emulsion. It was clarified that the supercooling rate of dispersed water particles in emulsion shows the larger value than that of the bulk water.

Latent palmprint matching.

PubMed

Jain, Anil K; Feng, Jianjiang

2009-06-01

The evidential value of palmprints in forensic applications is clear as about 30 percent of the latents recovered from crime scenes are from palms. While biometric systems for palmprint-based personal authentication in access control type of applications have been developed, they mostly deal with low-resolution (about 100 ppi) palmprints and only perform full-to-full palmprint matching. We propose a latent-to-full palmprint matching system that is needed in forensic applications. Our system deals with palmprints captured at 500 ppi (the current standard in forensic applications) or higher resolution and uses minutiae as features to be compatible with the methodology used by latent experts. Latent palmprint matching is a challenging problem because latent prints lifted at crime scenes are of poor image quality, cover only a small area of the palm, and have a complex background. Other difficulties include a large number of minutiae in full prints (about 10 times as many as fingerprints), and the presence of many creases in latents and full prints. A robust algorithm to reliably estimate the local ridge direction and frequency in palmprints is developed. This facilitates the extraction of ridge and minutiae features even in poor quality palmprints. A fixed-length minutia descriptor, MinutiaCode, is utilized to capture distinctive information around each minutia and an alignment-based minutiae matching algorithm is used to match two palmprints. Two sets of partial palmprints (150 live-scan partial palmprints and 100 latent palmprints) are matched to a background database of 10,200 full palmprints to test the proposed system. Despite the inherent difficulty of latent-to-full palmprint matching, rank-1 recognition rates of 78.7 and 69 percent, respectively, were achieved in searching live-scan partial palmprints and latent palmprints against the background database.

Real-time complex event processing for cloud resources

NASA Astrophysics Data System (ADS)

Adam, M.; Cordeiro, C.; Field, L.; Giordano, D.; Magnoni, L.

2017-10-01

The ongoing integration of clouds into the WLCG raises the need for detailed health and performance monitoring of the virtual resources in order to prevent problems of degraded service and interruptions due to undetected failures. When working in scale, the existing monitoring diversity can lead to a metric overflow whereby the operators need to manually collect and correlate data from several monitoring tools and frameworks, resulting in tens of different metrics to be constantly interpreted and analyzed per virtual machine. In this paper we present an ESPER based standalone application which is able to process complex monitoring events coming from various sources and automatically interpret data in order to issue alarms upon the resources’ statuses, without interfering with the actual resources and data sources. We will describe how this application has been used with both commercial and non-commercial cloud activities, allowing the operators to quickly be alarmed and react to misbehaving VMs and LHC experiments’ workflows. We will present the pattern analysis mechanisms being used, as well as the surrounding Elastic and REST API interfaces where the alarms are collected and served to users.

Corrosion/erosion detection of boiler tubes utilizing pulsed infrared imaging

NASA Astrophysics Data System (ADS)

Bales, Maurice J.; Bishop, Chip C.

1995-05-01

This paper discusses a new technique for locating and detecting wall thickness reduction in boiler tubes caused by erosion/corrosion. Traditional means for this type of defect detection utilizes ultrasonics (UT) to perform a point by point measurement at given intervals of the tube length, which requires extensive and costly shutdown or `outage' time to complete the inspection, and has led to thin areas going undetected simply because they were located in between the sampling points. Pulsed infrared imaging (PII) can provide nearly 100% inspection of the tubes in a fraction of the time needed for UT. The IR system and heat source used in this study do not require any special access or fixed scaffolding, and can be remotely operated from a distance of up to 100 feet. This technique has been tried experimentally in a laboratory environment and verified in an actual field application. Since PII is a non-contact technique, considerable time and cost savings should be realized as well as the ability to predict failures rather than repairing them once they have occurred.

An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.

PubMed

Sobczyńska-Malefora, A; Ramachandran, R; Cregeen, D; Green, E; Bennett, P; Harrington, D J; Lemonde, H A

2017-08-01

The vitamin B 12 status of infants depends on maternal B 12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B 12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B 12 injections. Marked catch-up of developmental milestones was noted after treatment with B 12 . Investigations of parents showed normal B 12 in the father and combined B 12 and iron deficiency in the mother. Maternal B 12 deficiency, most likely masked by iron deficiency, led to severe B 12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B 12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B 12 status during pregnancy.

Mild traumatic brain injury: a midwest survey about the assessment and documentation practices of emergency department nurses.

PubMed

Bay, Esther

2011-01-01

Research reported that mild traumatic brain injury (MTBI), the most common neurological condition in the world, is often undetected in the emergency department. Failure to properly detect and offer treatment therapies has been linked to chronic complications such as, mood disorders and postconcussion syndrome. This descriptive study used a tailored survey (25.0% response rate) to determine emergency department nurses' practices for the assessment and documentation of persons with MTBI. The primary purpose was to determine the extent to which these practices were aligned with the Centers for Disease Control and Prevention guidelines contained within the Acute Concussion Evaluation care plan. Results indicated that physical and cognitive symptoms were assessed and documented more than emotional or sleep symptoms. Still, some cognitive and physical symptoms were rarely assessed or documented. Focus seemed to be on ruling out more severe brain injury versus detection of a mild brain injury. Aligning the systematic assessment and documentation of persons with suspected concussion MTBI with recommendations from the Centers for Disease Control and Prevention is suggested.

Pathogenesis of occult chronic hepatitis B virus infection

PubMed Central

de la Fuente, Rocio Aller; Gutiérrez, María L; Garcia-Samaniego, Javier; Fernández-Rodriguez, Conrado; Lledó, Jose Luis; Castellano, Gregorio

2011-01-01

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this “occult” HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma. PMID:21472118

Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism

PubMed Central

Jeanne, Nicolas; Saliou, Adrien; Carcenac, Romain; Lefebvre, Caroline; Dubois, Martine; Cazabat, Michelle; Nicot, Florence; Loiseau, Claire; Raymond, Stéphanie; Izopet, Jacques; Delobel, Pierre

2015-01-01

HIV-1 coreceptor usage must be accurately determined before starting CCR5 antagonist-based treatment as the presence of undetected minor CXCR4-using variants can cause subsequent virological failure. Ultra-deep pyrosequencing of HIV-1 V3 env allows to detect low levels of CXCR4-using variants that current genotypic approaches miss. However, the computation of the mass of sequence data and the need to identify true minor variants while excluding artifactual sequences generated during amplification and ultra-deep pyrosequencing is rate-limiting. Arbitrary fixed cut-offs below which minor variants are discarded are currently used but the errors generated during ultra-deep pyrosequencing are sequence-dependant rather than random. We have developed an automated processing of HIV-1 V3 env ultra-deep pyrosequencing data that uses biological filters to discard artifactual or non-functional V3 sequences followed by statistical filters to determine position-specific sensitivity thresholds, rather than arbitrary fixed cut-offs. It allows to retain authentic sequences with point mutations at V3 positions of interest and discard artifactual ones with accurate sensitivity thresholds. PMID:26585833

Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism.

PubMed

Jeanne, Nicolas; Saliou, Adrien; Carcenac, Romain; Lefebvre, Caroline; Dubois, Martine; Cazabat, Michelle; Nicot, Florence; Loiseau, Claire; Raymond, Stéphanie; Izopet, Jacques; Delobel, Pierre

2015-11-20

HIV-1 coreceptor usage must be accurately determined before starting CCR5 antagonist-based treatment as the presence of undetected minor CXCR4-using variants can cause subsequent virological failure. Ultra-deep pyrosequencing of HIV-1 V3 env allows to detect low levels of CXCR4-using variants that current genotypic approaches miss. However, the computation of the mass of sequence data and the need to identify true minor variants while excluding artifactual sequences generated during amplification and ultra-deep pyrosequencing is rate-limiting. Arbitrary fixed cut-offs below which minor variants are discarded are currently used but the errors generated during ultra-deep pyrosequencing are sequence-dependant rather than random. We have developed an automated processing of HIV-1 V3 env ultra-deep pyrosequencing data that uses biological filters to discard artifactual or non-functional V3 sequences followed by statistical filters to determine position-specific sensitivity thresholds, rather than arbitrary fixed cut-offs. It allows to retain authentic sequences with point mutations at V3 positions of interest and discard artifactual ones with accurate sensitivity thresholds.

Social Stress and the Reactivation of Latent Herpes Simplex Virus Type 1

NASA Astrophysics Data System (ADS)

Padgett, David A.; Sheridan, John F.; Dorne, Julianne; Berntson, Gary G.; Candelora, Jessica; Glaser, Ronald

1998-06-01

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpes-viruses.

Effect of Melt Superheating Treatment on the Latent Heat Release of Sn

NASA Astrophysics Data System (ADS)

Xu, Junfeng; Dang, Bo; Fan, Dandan; Jian, Zengyun

2017-03-01

The accuracy of the baseline evaluation is of importance for calculating the transition enthalpy such as the latent heat of the crystallization. This study demonstrates the modified method of the equivalent non-latent heat baseline, by which the transition enthalpy can be measured accurately according to the transition peak in differential scanning calorimetric curve. With this method, the effect of melt superheating treatment time on the latent heat release upon the solidification of tin is investigated. The results show that the latent heat increases by increasing the treatment time, and is close to a constant when the treatment time is large enough, indicating the homogeneous system. And then, a simple model is established to describe the changes of the crystallization latent heat with the treatment time, which is confirmed by the experimental data of Sn.

Release of active TGF-β1 from the Latent TGF-β1/GARP complex on T regulatory cells is mediated by Integrin β81

PubMed Central

Edwards, Justin P.; Thornton, Angela M.; Shevach, Ethan M.

2014-01-01

Activated T regulatory cells (Treg) express latent TGF-β1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF-β1 from the complex of latent TGF-β1 and latent TGF-β1 binding protein, their role in processing latent TGF-β1 from the latent TGF-β1/GARP complex is unclear. Mouse CD4+Foxp3+ Treg, but not CD4+Foxp3− T cells, expressed integrin β8 (Itgb8) as detected by qRT-PCR. Itgb8 expression was a marker of thymically-derived (t)Treg, as it could not be detected on Foxp3+Helios− Tregs or on Foxp3+ T cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal suppressor function in vitro and in vivo in a model of colitis, but failed to provide TGF-β1 to drive Th17 or iTreg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-β1 on their cell surface consistent with defective processing. Thus, integrin αvβ8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF-β1 from the latent TGF-β1/GARP complex on the surface of tTregs. PMID:25127859

Modeling Psychological Attributes in Psychology – An Epistemological Discussion: Network Analysis vs. Latent Variables

PubMed Central

Guyon, Hervé; Falissard, Bruno; Kop, Jean-Luc

2017-01-01

Network Analysis is considered as a new method that challenges Latent Variable models in inferring psychological attributes. With Network Analysis, psychological attributes are derived from a complex system of components without the need to call on any latent variables. But the ontological status of psychological attributes is not adequately defined with Network Analysis, because a psychological attribute is both a complex system and a property emerging from this complex system. The aim of this article is to reappraise the legitimacy of latent variable models by engaging in an ontological and epistemological discussion on psychological attributes. Psychological attributes relate to the mental equilibrium of individuals embedded in their social interactions, as robust attractors within complex dynamic processes with emergent properties, distinct from physical entities located in precise areas of the brain. Latent variables thus possess legitimacy, because the emergent properties can be conceptualized and analyzed on the sole basis of their manifestations, without exploring the upstream complex system. However, in opposition with the usual Latent Variable models, this article is in favor of the integration of a dynamic system of manifestations. Latent Variables models and Network Analysis thus appear as complementary approaches. New approaches combining Latent Network Models and Network Residuals are certainly a promising new way to infer psychological attributes, placing psychological attributes in an inter-subjective dynamic approach. Pragmatism-realism appears as the epistemological framework required if we are to use latent variables as representations of psychological attributes. PMID:28572780

The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure.

PubMed

Nishikimi, Toshio; Ikeda, Masashi; Takeda, Yosuke; Ishimitsu, Toshihiko; Shibasaki, Ikuko; Fukuda, Hirotsugu; Kinoshita, Hideyuki; Nakagawa, Yasuaki; Kuwahara, Koichiro; Nakao, Kazuwa

2012-01-01

Pro-brain natriuretic peptide (proBNP)-108 and N-terminal proBNP-76 (NT-BNP) contain seven sites for O-linked oligosaccharide attachment. Currently, levels of glycosylated NT-BNP are probably underestimated because it is not recognised by one antibody in the sandwich assay system. The pathophysiological significance of cardiac and plasma levels of non-glycosylated (nonglyNT-BNP) and glycosylated NT-BNP (glyNT-BNP) in heart failure (HF) and chronic renal failure (CRF) was investigated. Plasma samples from 186 patients with HF and 76 patients with CRF on haemodialysis were studied, together with 11 atrial tissue samples. To measure nonglyNT-BNP and glyNT-BNP, samples were incubated with or without deglycosylating enzymes and NT-BNP was measured using Roche Elecsys proBNP I. The percentage glyNT-BNP was calculated as glyNT-BNP/(glyNT-BNP + nonglyNT-BNP). In HF, plasma BNP, nonglyNT-BNP and glyNT-BNP levels all increased with increasing disease severity (New York Heart Association class; p<0.0001), though the molar ratio remained constant (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:2.4:9.6). Before haemodialysis for CRF, plasma BNP and nonglyNT-BNP were somewhat elevated, and glyNT-BNP was markedly increased (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:8.5:82). After haemodialysis, plasma BNP, nonglyNT-BNP, atrial natriuretic protein and cGMP all declined (p<0.0001), but glyNT-BNP was unchanged. Notably, the percentage of glyNT-BNP was elevated before haemodialysis, and was further increased after haemodialysis (p<0.0001). Atrial tissue levels of BNP, nonglyNT-BNP and glyNT-BNP were similar. THE findings suggest that most endogenous plasma NT-BNP is glycosylated and therefore undetectable with the current assay system, and that the relative glycosylation level is increased by haemodialysis.

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

PubMed

Mak, Chloe Miu; Lam, Ching-Wan; Chim, Stella; Siu, Tak-Shing; Ng, King-Fai; Tam, Sidney

2013-01-01

Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France.

PubMed

Aherfi, Sarah; Solas, Caroline; Motte, Anne; Moreau, Jacques; Borentain, Patrick; Mokhtari, Saadia; Botta-Fridlund, Danielle; Dhiver, Catherine; Portal, Isabelle; Ruiz, Jean-Marie; Ravaux, Isabelle; Bregigeon, Sylvie; Poizot-Martin, Isabelle; Stein, Andreas; Gérolami, René; Brouqui, Philippe; Tamalet, Catherine; Colson, Philippe

2014-11-01

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy. © 2014 Wiley Periodicals, Inc.

Ultra-sensitive PSA Following Prostatectomy Reliably Identifies Patients Requiring Post-Op Radiotherapy

PubMed Central

Kang, Jung Julie; Reiter, Robert; Steinberg, Michael; King, Christopher R.

2015-01-01

PURPOSE Integrating ultra-sensitive PSA (uPSA) into surveillance of high-risk patients following radical prostatectomy (RP) potentially optimizes management by correctly identifying actual recurrences, promoting an early salvage strategy and minimizing overtreatment. The power of uPSA following surgery to identify eventual biochemical failures is tested. PATIENTS AND METHODS From 1991–2013, 247 high-risk patients with a median follow-up was 44 months after RP were identified (extraprostatic extension and/or positive margin). Surgical technique, initial PSA (iPSA), pathology and post-op PSA were analyzed. The uPSA assay threshold was 0.01 ng/mL. Conventional biochemical relapse (cBCR) was defined as PSA ≥0.2 ng/mL. Kaplan Meier and Cox multivariate analyses (MVA) compared uPSA recurrence vs. cBCR rates. RESULTS Sensitivity analysis identified uPSA ≥0.03 as the optimal threshold identifying recurrence. First post-op uPSA ≥0.03, Gleason grade, T-stage, iPSA, and margin status predicted cBCR. On MVA, only first post-op uPSA ≥0.03, Gleason grade, and T-stage independently predicted cBCR. First post-op uPSA ≥0.03 conferred the highest risk (HR 8.5, p<0.0001) and discerned cBCR with greater sensitivity than undetectable first conventional PSA (70% vs. 46%). Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition. CONCLUSION uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage. uPSA enables critical decisions regarding timing and indication for post-op RT among high-risk patients following RP. PMID:25463990

Cirrhosis and Rapid Virological Response to Peginterferon Plus Ribavirin Determine Treatment Outcome in HCV-1 IL28B rs12979860 CC Patients

PubMed Central

Aghemo, Alessio; Degasperi, Elisabetta; Rumi, Maria Grazia; Galmozzi, Enrico; Valenti, Luca; De Francesco, Raffaele; De Nicola, Stella; Cheroni, Cristina; Grassi, Eleonora; Colombo, Massimo

2013-01-01

Background. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated. Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients. Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed. Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69%) achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07–6.21) as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics (P = 0.03). HCV RNA undetectability (<50 IU/mL) at week 4 (RVR) was achieved by 58 patients (53%). The SVR rates were independent of RVR in noncirrhotics, 76% (34/45) RVR (+) and 74% (25/34) RVR (−) (P = 0.9). In cirrhotic patients, SVR rates were significantly higher in RVR (+) compared to RVR (−) (10/13 (77%) versus 6/17 (35%) P = 0.03). Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy. PMID:23936821

Performance characteristics of finger-stick dried blood spots (DBS) on the determination of human immunodeficiency virus (HIV) treatment failure in a pediatric population in Mozambique

PubMed Central

Chang, Joy; de Sousa, Amina; Sabatier, Jennifer; Assane, Mariamo; Zhang, Guoqing; Bila, Dulce; Vaz, Paula; Alfredo, Charity; Cossa, Loide; Bhatt, Nilesh; Koumans, Emilia H.; Yang, Chunfu; Rivadeneira, Emilia; Jani, Ilesh; Houston, James C.

2017-01-01

Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott’s VL test with a paired plasma sample using Roche’s VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing. PMID:28704560

Development of a structural health monitoring system for the life assessment of critical transportation infrastructure.

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

Roach, Dennis Patrick; Jauregui, David Villegas; Daumueller, Andrew Nicholas

2012-02-01

Recent structural failures such as the I-35W Mississippi River Bridge in Minnesota have underscored the urgent need for improved methods and procedures for evaluating our aging transportation infrastructure. This research seeks to develop a basis for a Structural Health Monitoring (SHM) system to provide quantitative information related to the structural integrity of metallic structures to make appropriate management decisions and ensuring public safety. This research employs advanced structural analysis and nondestructive testing (NDT) methods for an accurate fatigue analysis. Metal railroad bridges in New Mexico will be the focus since many of these structures are over 100 years old andmore » classified as fracture-critical. The term fracture-critical indicates that failure of a single component may result in complete collapse of the structure such as the one experienced by the I-35W Bridge. Failure may originate from sources such as loss of section due to corrosion or cracking caused by fatigue loading. Because standard inspection practice is primarily visual, these types of defects can go undetected due to oversight, lack of access to critical areas, or, in riveted members, hidden defects that are beneath fasteners or connection angles. Another issue is that it is difficult to determine the fatigue damage that a structure has experienced and the rate at which damage is accumulating due to uncertain history and load distribution in supporting members. A SHM system has several advantages that can overcome these limitations. SHM allows critical areas of the structure to be monitored more quantitatively under actual loading. The research needed to apply SHM to metallic structures was performed and a case study was carried out to show the potential of SHM-driven fatigue evaluation to assess the condition of critical transportation infrastructure and to guide inspectors to potential problem areas. This project combines the expertise in transportation infrastructure at New Mexico State University with the expertise at Sandia National Laboratories in the emerging field of SHM.« less

TRMM Data from the Goddard Earth Sciences (GES) DISC DAAC: Tropical Rainfall Measuring Mission (TRMM)

NASA Technical Reports Server (NTRS)

2003-01-01

Tropical rainfall affects the lives and economies of a majority of the Earth's population. Tropical rain systems, such as hurricanes, typhoons, and monsoons, are crucial to sustaining the livelihoods of those living in the tropics. Excess rainfall can cause floods and great property and crop damage, whereas too little rainfall can cause drought and crop failure. The latent heat release during the process of precipitation is a major source of energy that drives the atmospheric circulation. This latent heat can intensify weather systems, affecting weather thousands of kilometers away, thus making tropical rainfall an important indicator of atmospheric circulation and short-term climate change. The Tropical Rainfall Measuring Mission (TRMM), jointly sponsored by the National Aeronautics and Space Administration (NASA) of the United States and the National Space Development Agency (NASDA) of Japan, provides visible, infrared, and microwave observations of tropical and subtropical rain systems. The satellite observations are complemented by ground radar and rain gauge measurements to validate satellite rain estimation techniques. Goddard Space Flight Center's involvement includes the observatory, four instruments, integration and testing of the observatory, data processing and distribution, and satellite operations. TRMM has a design lifetime of three years. It is currently in its fifth year of operation. Data generated from TRMM and archived at the GES DAAC are useful not only for hydrologists, atmospheric scientists, and climatologists, but also for the health community studying infectious diseases, the ocean research community, and the agricultural community.

Genetic Complexity of Episodic Memory: A Twin Approach to Studies of Aging

PubMed Central

Kremen, William S.; Spoon, Kelly M.; Jacobson, Kristen C.; Vasilopoulos, Terrie; McCaffery, Jeanne M.; Panizzon, Matthew S.; Franz, Carol E.; Vuoksimaa, Eero; Xian, Hong; Rana, Brinda K.; Toomey, Rosemary; McKenzie, Ruth; Lyons, Michael J.

2016-01-01

Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if “memory is memory” and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory. PMID:24956007

Abscisic acid is not necessary for gravitropism in primary roots of Zea mays

NASA Technical Reports Server (NTRS)

Moore, R.

1990-01-01

Primary roots of Zea mays L. cv. Tx 5855 treated with fluridone are strongly graviresponsive, but have undetectable levels of abscisic acid (ABA). Primary roots of the carotenoid-deficient w-3, vp-5, and vp-7 mutants of Z. mays are also graviresponsive despite having undetectable amounts of ABA. Graviresponsive roots of untreated and wild-type seedlings contain 286 to 317 ng ABA g-1 f. wt, respectively. These results indicate that ABA is not necessary for root gravicurvature.

Perfect Undetectable Acoustic Device from Fabry-Pérot Resonances

NASA Astrophysics Data System (ADS)

Chen, Huanyang; Zhou, Yangyang; Zhou, Mengying; Xu, Lin; Liu, Qing Huo

2018-02-01

Transformation acoustics is a method to design novel acoustic devices, while the complexity of the material parameters hinders its progress. In this paper, we analytically present a three-dimensional perfect undetectable acoustic device from Fabry-Pérot resonances and confirm its functionality from Mie theory. Such a mechanism goes beyond the traditional transformation acoustics. In addition, such a reduced version can be realized by holey-structured metamaterials. Our theory paves a way to the implementation of three-dimensional transformation acoustic devices.

Flexible Modeling of Latent Task Structures in Multitask Learning

DTIC Science & Technology

2012-06-26

Flexible Modeling of Latent Task Structures in Multitask Learning Alexandre Passos† apassos@cs.umass.edu Computer Science Department, University of...of Maryland, College Park, MD USA Abstract Multitask learning algorithms are typically designed assuming some fixed, a priori known latent structure...shared by all the tasks. However, it is usually unclear what type of latent task structure is the most ap- propriate for a given multitask learning prob

Computational Evaluation of a Latent Heat Energy Storage System

DTIC Science & Technology

2013-01-01

alternative to conventional photovoltaic panels paired with electrochemical batteries , has at the core of its design a latent heat based energy...The proposed system, an alternative to conventional photovoltaic panels paired with electrochemical batteries , has at the core of its design a latent...somewhat for certain niches in which material cost is less of a concern. Current latent heat storage systems typically use paraffin compounds or salt

Latent fingerprint matching.

PubMed

Jain, Anil K; Feng, Jianjiang

2011-01-01

Latent fingerprint identification is of critical importance to law enforcement agencies in identifying suspects: Latent fingerprints are inadvertent impressions left by fingers on surfaces of objects. While tremendous progress has been made in plain and rolled fingerprint matching, latent fingerprint matching continues to be a difficult problem. Poor quality of ridge impressions, small finger area, and large nonlinear distortion are the main difficulties in latent fingerprint matching compared to plain or rolled fingerprint matching. We propose a system for matching latent fingerprints found at crime scenes to rolled fingerprints enrolled in law enforcement databases. In addition to minutiae, we also use extended features, including singularity, ridge quality map, ridge flow map, ridge wavelength map, and skeleton. We tested our system by matching 258 latents in the NIST SD27 database against a background database of 29,257 rolled fingerprints obtained by combining the NIST SD4, SD14, and SD27 databases. The minutiae-based baseline rank-1 identification rate of 34.9 percent was improved to 74 percent when extended features were used. In order to evaluate the relative importance of each extended feature, these features were incrementally used in the order of their cost in marking by latent experts. The experimental results indicate that singularity, ridge quality map, and ridge flow map are the most effective features in improving the matching accuracy.

Bayesian latent structure modeling of walking behavior in a physical activity intervention

PubMed Central

Lawson, Andrew B; Ellerbe, Caitlyn; Carroll, Rachel; Alia, Kassandra; Coulon, Sandra; Wilson, Dawn K; VanHorn, M Lee; St George, Sara M

2017-01-01

The analysis of walking behavior in a physical activity intervention is considered. A Bayesian latent structure modeling approach is proposed whereby the ability and willingness of participants is modeled via latent effects. The dropout process is jointly modeled via a linked survival model. Computational issues are addressed via posterior sampling and a simulated evaluation of the longitudinal model’s ability to recover latent structure and predictor effects is considered. We evaluate the effect of a variety of socio-psychological and spatial neighborhood predictors on the propensity to walk and the estimation of latent ability and willingness in the full study. PMID:24741000

Care 3 phase 2 report, maintenance manual

NASA Technical Reports Server (NTRS)

Bryant, L. A.; Stiffler, J. J.

1982-01-01

CARE 3 (Computer-Aided Reliability Estimation, version three) is a computer program designed to help estimate the reliability of complex, redundant systems. Although the program can model a wide variety of redundant structures, it was developed specifically for fault-tolerant avionics systems--systems distinguished by the need for extremely reliable performance since a system failure could well result in the loss of human life. It substantially generalizes the class of redundant configurations that could be accommodated, and includes a coverage model to determine the various coverage probabilities as a function of the applicable fault recovery mechanisms (detection delay, diagnostic scheduling interval, isolation and recovery delay, etc.). CARE 3 further generalizes the class of system structures that can be modeled and greatly expands the coverage model to take into account such effects as intermittent and transient faults, latent faults, error propagation, etc.

Cultural variation of perceptions of crew behaviour in multi-pilot aircraft.

PubMed

Hörmann, H J

2001-09-01

As the "last line of defence" pilots in commercial aviation often have to counteract effects of unexpected system flaws that could endanger the safety of a given flight. In order to timely detect and mitigate consequences of latent or active failures, effective team behaviour of the crew members is an indispensable condition. While this fact is generally agreed in the aviation community, there seems to be a wide range of concepts how crews should interact most effectively. Within the framework of the European project JARTEL the cultural robustness of evaluations of crew behaviour was examined. 105 instructor pilots from 14 different airlines representing 12 European countries participated in this project. The instructors' evaluations of crew behaviours in eight video scenarios will be compared in relation to cultural differences on Hofstede's dimensions of Power Distance and Individualism.

Latent Tricuspid Valve Rupture after Motor Vehicle Accident and Routine Echocardiography in All Chest-Wall Traumas

PubMed Central

Khurana, Suchi; Puri, Rishi; Wong, Dennis; Dundon, Benjamin K.; Brown, Michael A.; Worthley, Matthew I.; Worthley, Stephen G.

2009-01-01

Blunt chest-wall trauma is common; however, resultant tricuspid valve rupture is rare and can be subtle in its presentation. Transthoracic echocardiography plays a key role in diagnosis. Herein, we report the case of a 42-year-old woman who sustained substantial chest-wall trauma in a high-speed motor vehicle accident. She presented a week later with symptoms of right-heart failure, secondary to flail tricuspid valve leaflets and torrential tricuspid regurgitation. The case of this patient highlights the importance of early diagnosis and elicits discussion of the mechanisms that can underlie delayed tricuspid valve rupture. Because the clinical diagnosis of tricuspid valve rupture can be difficult, we believe that echocardiography should be used early and, if necessary, repeatedly in all patients who sustain blunt chest-wall trauma. PMID:20069094

Uncooled pump combiners for fiber laser and amplifier systems

NASA Astrophysics Data System (ADS)

Bansal, L.; Sienkowski, R.; Neale, C.; Mann, J.; Headley, C.

2018-02-01

In this work we demonstrate a high transmission pump combiner that can operate uncooled at a maximum power of 400W for a continuous duration of 100hrs. The 7x1 pump combiner has seven 105/125 μm diameter 0.22 NA input pump fibers and a 247 μm diameter and 0.22 NA glass clad output fiber. The combiner has a high, 99%, pump transmission efficiency. These devices withstand without failure, a series of environmental stress tests, namely Thermal Cycling (-40 to 85ºC) and Damp Humidity (85ºC/85RH). These tests are conducted to uncover any latent defects in the device structure. The combiner's also survive an elevated temperature of 75ºC at a power of 365W for duration of 5hrs, without any noticeable change in pump transmission.

Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

PubMed

Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

2017-10-17

The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

NASA Astrophysics Data System (ADS)

Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

2015-10-01

Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

A general class of multinomial mixture models for anuran calling survey data

USGS Publications Warehouse

Royle, J. Andrew; Link, W.A.

2005-01-01

We propose a general framework for modeling anuran abundance using data collected from commonly used calling surveys. The data generated from calling surveys are indices of calling intensity (vocalization of males) that do not have a precise link to actual population size and are sensitive to factors that influence anuran behavior. We formulate a model for calling-index data in terms of the maximum potential calling index that could be observed at a site (the 'latent abundance class'), given its underlying breeding population, and we focus attention on estimating the distribution of this latent abundance class. A critical consideration in estimating the latent structure is imperfect detection, which causes the observed abundance index to be less than or equal to the latent abundance class. We specify a multinomial sampling model for the observed abundance index that is conditional on the latent abundance class. Estimation of the latent abundance class distribution is based on the marginal likelihood of the index data, having integrated over the latent class distribution. We apply the proposed modeling framework to data collected as part of the North American Amphibian Monitoring Program (NAAMP).

Using SAS PROC CALIS to fit Level-1 error covariance structures of latent growth models.

PubMed

Ding, Cherng G; Jane, Ten-Der

2012-09-01

In the present article, we demonstrates the use of SAS PROC CALIS to fit various types of Level-1 error covariance structures of latent growth models (LGM). Advantages of the SEM approach, on which PROC CALIS is based, include the capabilities of modeling the change over time for latent constructs, measured by multiple indicators; embedding LGM into a larger latent variable model; incorporating measurement models for latent predictors; and better assessing model fit and the flexibility in specifying error covariance structures. The strength of PROC CALIS is always accompanied with technical coding work, which needs to be specifically addressed. We provide a tutorial on the SAS syntax for modeling the growth of a manifest variable and the growth of a latent construct, focusing the documentation on the specification of Level-1 error covariance structures. Illustrations are conducted with the data generated from two given latent growth models. The coding provided is helpful when the growth model has been well determined and the Level-1 error covariance structure is to be identified.

Comparing the Performance of Improved Classify-Analyze Approaches For Distal Outcomes in Latent Profile Analysis

PubMed Central

Dziak, John J.; Bray, Bethany C.; Zhang, Jieting; Zhang, Minqiang; Lanza, Stephanie T.

2016-01-01

Several approaches are available for estimating the relationship of latent class membership to distal outcomes in latent profile analysis (LPA). A three-step approach is commonly used, but has problems with estimation bias and confidence interval coverage. Proposed improvements include the correction method of Bolck, Croon, and Hagenaars (BCH; 2004), Vermunt’s (2010) maximum likelihood (ML) approach, and the inclusive three-step approach of Bray, Lanza, & Tan (2015). These methods have been studied in the related case of latent class analysis (LCA) with categorical indicators, but not as well studied for LPA with continuous indicators. We investigated the performance of these approaches in LPA with normally distributed indicators, under different conditions of distal outcome distribution, class measurement quality, relative latent class size, and strength of association between latent class and the distal outcome. The modified BCH implemented in Latent GOLD had excellent performance. The maximum likelihood and inclusive approaches were not robust to violations of distributional assumptions. These findings broadly agree with and extend the results presented by Bakk and Vermunt (2016) in the context of LCA with categorical indicators. PMID:28630602

Latent mnemonic strengths are latent: a comment on Mickes, Wixted, and Wais (2007).

PubMed

Rouder, Jeffrey N; Pratte, Michael S; Morey, Richard D

2010-06-01

Mickes, Wixted, and Wais (2007) proposed a simple test of latent strength variability in recognition memory. They asked participants to rate their confidence using either a 20-point or a 99-point strength scale and plotted distributions of the resulting ratings. They found 25% more variability in ratings for studied than for new items, which they interpreted as providing evidence that latent mnemonic strength distributions are 25% more variable for studied than for new items. We show here that this conclusion is critically dependent on assumptions--so much so that these assumptions determine the conclusions. In fact, opposite conclusions, such that study does not affect the variability of latent strength, may be reached by making different but equally plausible assumptions. Because all measurements of mnemonic strength variability are critically dependent on untestable assumptions, all are arbitrary. Hence, there is no principled method for assessing the relative variability of latent mnemonic strength distributions.

Long-Term Resolution of Viral Breakthrough after Changing HIV Viral Load Assay.

PubMed

Obeid, Karam M; Sural, Preethi; Szpunar, Susan; Johnson, Leonard B

2011-01-01

Viral load (VL) measurement assays differ in their sensitivity with polymerase chain reaction assays (PCR) being more sensitive than branched DNA (bDNA) assays. We evaluated virologic outcomes of patients and physicians' response to increased VL after a switch from bDNA to PCR assay. Retrospective, case-control study on 65 HIV+ patients receiving highly active antiretroviral therapy (HAART). Cases included patients with undetectable VL by bDNA that became detectable after the switch; controls were patients that remained undetectable. Records were reviewed up to 1 year after the switch. A total of 58.5% patients had detectable VL after the switch. Repeat VL testing and resistance testing were ordered in 15.4% and 23.1% of these patients, respectively. By 1 year, VL was undetectable in 82.8% of cases and 92% of controls (P = .30), without change in HAART. Transient viremia after changing VL assay reflects the different sensitivity of these assays with no impact on patients' outcomes compared to controls.

Development, Testing, and Failure Mechanisms of a Replicative Ice Phase Change Material Heat Exchanger

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Hansen, Scott; Stephan, Ryan A.

2009-01-01

Phase change materials (PCM) may be useful for thermal control systems that involve cyclical heat loads or cyclical thermal environments such as Low Earth Orbit (LEO) and Low Lunar Orbit (LLO). Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. One advantage that PCM s have over evaporators in this scenario is that they do not use a consumable. Wax PCM units have been baselined for the Orion thermal control system and also provide risk mitigation for the Altair Lander. However, the use of water as a PCM has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. An ice PCM heat exchanger that replicates the thermal energy storage capacity of an existing wax PCM unit was fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion are investigated. This paper presents the results to date of this investigation.

Development, Testing, and Failure Mechanisms of a Replicative Ice Phase Change Material Heat Exchanger

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Hansen, Scott; Stephan, Ryan A.

2010-01-01

Phase change materials (PCM) may be useful for thermal control systems that involve cyclical heat loads or cyclical thermal environments such as Low Earth Orbit (LEO) and Low Lunar Orbit (LLO). Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. One advantage that PCM's have over evaporators in this scenario is that they do not use a consumable. Wax PCM units have been baselined for the Orion thermal control system and also provide risk mitigation for the Altair Lander. However, the use of water as a PCM has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. An ice PCM heat exchanger that replicates the thermal energy storage capacity of an existing wax PCM unit was fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion are investigated. This paper presents the results to date of this investigation. Nomenclature

Understanding the causes of intravenous medication administration errors in hospitals: a qualitative critical incident study

PubMed Central

Keers, Richard N; Williams, Steven D; Cooke, Jonathan; Ashcroft, Darren M

2015-01-01

Objectives To investigate the underlying causes of intravenous medication administration errors (MAEs) in National Health Service (NHS) hospitals. Setting Two NHS teaching hospitals in the North West of England. Participants Twenty nurses working in a range of inpatient clinical environments were identified and recruited using purposive sampling at each study site. Primary outcome measures Semistructured interviews were conducted with nurse participants using the critical incident technique, where they were asked to discuss perceived causes of intravenous MAEs that they had been directly involved with. Transcribed interviews were analysed using the Framework approach and emerging themes were categorised according to Reason's model of accident causation. Results In total, 21 intravenous MAEs were discussed containing 23 individual active failures which included slips and lapses (n=11), mistakes (n=8) and deliberate violations of policy (n=4). Each active failure was associated with a range of error and violation provoking conditions. The working environment was implicated when nurses lacked healthcare team support and/or were exposed to a perceived increased workload during ward rounds, shift changes or emergencies. Nurses frequently reported that the quality of intravenous dose-checking activities was compromised due to high perceived workload and working relationships. Nurses described using approaches such as subconscious functioning and prioritising to manage their duties, which at times contributed to errors. Conclusions Complex interactions between active and latent failures can lead to intravenous MAEs in hospitals. Future interventions may need to be multimodal in design in order to mitigate these risks and reduce the burden of intravenous MAEs. PMID:25770226

Digital Sensor Technology

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

Thomas, Ken D.; Quinn, Edward L.; Mauck, Jerry L.

The nuclear industry has been slow to incorporate digital sensor technology into nuclear plant designs due to concerns with digital qualification issues. However, the benefits of digital sensor technology for nuclear plant instrumentation are substantial in terms of accuracy and reliability. This paper, which refers to a final report issued in 2013, demonstrates these benefits in direct comparisons of digital and analog sensor applications. Improved accuracy results from the superior operating characteristics of digital sensors. These include improvements in sensor accuracy and drift and other related parameters which reduce total loop uncertainty and thereby increase safety and operating margins. Anmore » example instrument loop uncertainty calculation for a pressure sensor application is presented to illustrate these improvements. This is a side-by-side comparison of the instrument loop uncertainty for both an analog and a digital sensor in the same pressure measurement application. Similarly, improved sensor reliability is illustrated with a sample calculation for determining the probability of failure on demand, an industry standard reliability measure. This looks at equivalent analog and digital temperature sensors to draw the comparison. The results confirm substantial reliability improvement with the digital sensor, due in large part to ability to continuously monitor the health of a digital sensor such that problems can be immediately identified and corrected. This greatly reduces the likelihood of a latent failure condition of the sensor at the time of a design basis event. Notwithstanding the benefits of digital sensors, there are certain qualification issues that are inherent with digital technology and these are described in the report. One major qualification impediment for digital sensor implementation is software common cause failure (SCCF).« less

A pilot evaluation of whole blood finger-prick sampling for point-of-care HIV viral load measurement: the UNICORN study.

PubMed

Fidler, Sarah; Lewis, Heather; Meyerowitz, Jodi; Kuldanek, Kristin; Thornhill, John; Muir, David; Bonnissent, Alice; Timson, Georgina; Frater, John

2017-10-20

There is a global need for HIV viral load point-of-care (PoC) assays to monitor patients receiving antiretroviral therapy. UNICORN was the first study of an off-label protocol using whole blood finger-prick samples tested with and without a simple three minute spin using a clinic-room microcentrifuge. Two PoC assays were evaluated in 40 HIV-positive participants, 20 with detectable and 20 with undetectable plasma viral load (pVL) (<20 copies/ml). Using 100 µl finger-prick blood samples, the Cepheid Xpert HIV-1 Viral Load and HIV-1 Qual cartridges were compared with laboratory pVL assessment (TaqMan, Roche). For participants with undetectable viraemia by TaqMan, there was poor concordance without centrifugation with the TaqMan platform with only 40% 'undetectable' using Xpert VL and 25% 'not detected' using the Qual assay. After a 3 minute spin, 100% of samples were undetectable using either assay, showing full concordance with the TaqMan assay. Defining a lower limit of detection of 1000 copies/ml when including a spin, there was 100% concordance with the TaqMan platform with strong correlation (rho 0.95 and 0.94; p < 0.0001 for both assays). When including a simple microcentrifugation step, finger-prick PoC testing was a quick and accurate approach for assessing HIV viraemia, with excellent concordance with validated laboratory approaches.

Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues

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

Lackner, A.A.; Rodriguez, M.H.; Bush, C.E.

1988-06-01

Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA,more » and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system.« less

Ultrasonic Inspection to Quantify Failure Pathologies of Crimped Electrical Connections

NASA Technical Reports Server (NTRS)

Cramer, K. Elliott; Perey, Daniel F.; Yost, William T.

2014-01-01

Previous work has shown that ultrasonic inspection provides a means of assessing electrical crimp quality that ensures the electrical and mechanical integrity of an initial crimp before the installation process is completed. The amplitude change of a compressional ultrasonic wave propagating at right angles to the wire axis and through the junction of a crimp termination was shown to correlate with the results of destructive pull tests, which is a standard for assessing crimp wire junction quality. Of additional concern are crimps made at high speed assembly lines for wiring harnesses, which are used for critical applications, such as in aircraft. During high-speed assembly it is possible that many faulty crimps go undetected until long after assembly, and fail in service. The position and speed of the crimping jaw become factors as the high-speed crimp is formed. The work presented in this paper is designed to cover the more difficult and more subtle area of high-speed crimps by taking into account the rate change of the measurements. Building on the previous work, we present an analysis methodology, based on transmitted ultrasonic energy and timing of the first received pulse that is shown to correlate to the gauge of the crimp/ferrule combination and the position of the crimping jaw. Results demonstrating the detectability of a number of the crimp failure pathologies, such as missing strands, partially inserted wires and incomplete crimp compression, are presented. The ability of this technique to estimate crimp height, a mechanical measure of crimp quality, is discussed.

Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency

PubMed Central

Arnold, Amy C.; Garland, Emily M.; Celedonio, Jorge E.; Raj, Satish R.; Abumrad, Naji N.; Biaggioni, Italo; Robertson, David; Luther, James M.

2017-01-01

Context: Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. Case Description: We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (−32 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 μU/mL), with normal glucose (91 mg/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis. Conclusions: We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism. PMID:27778639

Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency.

PubMed

Arnold, Amy C; Garland, Emily M; Celedonio, Jorge E; Raj, Satish R; Abumrad, Naji N; Biaggioni, Italo; Robertson, David; Luther, James M; Shibao, Cyndya A

2017-01-01

Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (-32 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 μU/mL), with normal glucose (91 mg/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis. We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism. Copyright © 2017 by the Endocrine Society

Current issues in the management of paediatric viral hepatitis.

PubMed

Yeung, Latifa T F; Roberts, Eve A

2010-01-01

Viral hepatitis poses important problems for children. In preschoolers, hepatitis A virus (HAV) infection frequently causes acute liver failure. Vaccinating toddlers against HAV in countries with high endemicity is expected to decrease mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus (HEV) may benefit fetal health, because pregnant women are most prone to acute liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate value and versatility for preventing serious liver disease. With chronic infection, undetectable levels of serum HBV DNA complement e-seroconversion as the preferred outcome measure; suppressed viral load correlates with long-term complications better than HBeAg status. Among Taiwanese children, low pretreatment HBV DNA (<2 x 10(8) copies/ml) strongly predicted response to interferon-alpha. Future paediatric studies must incorporate HBV DNA levels. The rationale for routine treatment of immunotolerant hepatitis B during childhood remains uncertain. Any treatment of chronic hepatitis B in childhood requires consideration of the risks and benefits. Childhood hepatitis C virus (HCV) infection results mainly from mother-to-infant transmission. Babies of HCV-infected women should be tested for serum HCV RNA at 1 month of age. If negative, confirmatory anti-HCV antibody testing may be performed between 12 and 15 months of age. Children with chronic hepatitis C may develop progressive fibrosis/cirrhosis, particularly in the setting of obesity and insulin resistance. Treatment of children chronically infected with genotype 2 or 3 is highly successful: combination therapy of pegylated interferon-alpha and ribavirin is well tolerated and superior to pegylated interferon-alpha alone.

Ultrasonic inspection to quantify failure pathologies of crimped electrical connections

NASA Astrophysics Data System (ADS)

Cramer, K. Elliott; Perey, Daniel F.; Yost, William T.

2015-03-01

Previous work has shown that ultrasonic inspection provides a means of assessing electrical crimp quality that ensures the electrical and mechanical integrity of an initial crimp before the installation process is completed. The amplitude change of a compressional ultrasonic wave propagating at right angles to the wire axis and through the junction of a crimp termination was shown to correlate with the results of destructive pull tests, which is a standard for assessing crimp wire junction quality. Of additional concern are crimps made at high speed assembly lines for wiring harnesses, which are used for critical applications, such as in aircraft. During high-speed assembly it is possible that many faulty crimps go undetected until long after assembly, and fail in service. The position and speed of the crimping jaw become factors as the high-speed crimp is formed. The work presented in this paper is designed to cover the more difficult and more subtle area of high-speed crimps by taking into account the rate change of the measurements. Building on the previous work, we present an analysis methodology, based on transmitted ultrasonic energy and timing of the first received pulse that is shown to correlate to the gauge of the crimp/ferrule combination and the position of the crimping jaw. Results demonstrating the detectability of a number of the crimp failure pathologies, such as missing strands, partially inserted wires and incomplete crimp compression, are presented. The ability of this technique to estimate crimp height, a mechanical measure of crimp quality, is discussed.

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

PubMed

Lam, Ming Kai; Sen, Hanim; Tandjung, Kenneth; van Houwelingen, K Gert; de Vries, Arie G; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Löwik, Marije M; Linssen, Gerard C M; Ijzerman, Maarten J; van der Palen, Job; Doggen, Carine J M; von Birgelen, Clemens

2014-04-01

To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

PubMed Central

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

Motivational profiles in high school students: Differences in behavioural and emotional homework engagement and academic achievement.

PubMed

Regueiro, Bibiana; Núñez, José C; Valle, Antonio; Piñeiro, Isabel; Rodríguez, Susana; Rosário, Pedro

2016-12-12

This work examined whether combinations of academic and non-academic goals generated different motivational profiles in high school students. Besides, differences in homework behavioural engagement (i.e. amount of homework, time spent in homework, homework time management), homework emotional engagement (i.e. homework anxiety) and academic achievement were analysed. Participants were 714 high school students (43.4% boys and 56.6% girls). The study of potential motivational profiles was conducted by latent profile analysis, and the differences between the motivational profiles regarding homework variables and academic achievement were analysed using multivariate analysis. The results indicate the existence of five groups of motivational profiles: a group of students with multiple goals, a group of unmotivated students, two groups of students with a predominance of learning goals and, finally, a group comprising students with a high fear of failure. Both the group with multiple goals and the learning goals-oriented groups reported to do more homework, spending more time on homework, making better use of that time and having a higher academic achievement than counterparts. The avoidance-failure group and the group with multiple goals showed higher levels of homework anxiety. Globally, these results provide support for a person-centred approach. © 2016 International Union of Psychological Science.

The Parable of the Boiled System Safety Professional: Drift to Failure

NASA Technical Reports Server (NTRS)

Shivers, C. Herbert

2011-01-01

Recall from the Parable of the Boiled Frog, that tossing a frog into boiling water causes the frog to jump out and hop away while placing a frog in suitable temperature water and slowly bringing the water to a boil results in the frog boiling due to not being aware of the slowly increasing danger, theoretically, of course. System safety professionals must guard against allowing dangers to creep unnoticed into their projects and be ever alert to notice signs of impending problems. People have used various phrases related to the idea, most notably, latent conditions, James Reason in Managing the Risks of Organizational Accidents (1, pp 10-11), Drift to Failure, Sydney Dekker (2, pp 82-86) in Resilience Engineering: Chronicling the Emergence of Confused Consensus in Resilience Engineering: Concepts and Precepts, Hollnagel, Woods and Leveson, and normalization of deviance, Diane Vaughan in The Challenger Launch Decision: Risky Technology, Culture, and Deviance at NASA (3). Reason also said, If eternal vigilance is the price of liberty, then chronic unease is the price of safety (1, p 37). Our challenge as system safety professionals is to be aware of the emergence of signals that warn us of slowly eroding safety margins. This paper will discuss how system safety professionals might better perform in that regard.

Experimental Investigation of Ice Phase Change Material Heat Exchangers

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Stephan, Ryan A.

2011-01-01

Phase change materials (PCM) may be useful for spacecraft thermal control systems that involve cyclical heat loads or cyclical thermal environments. Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. This can result in a decreased turndown ratio for the radiator and a reduced system mass. The use of water as a PCM rather than the more traditional paraffin wax has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. A number of ice PCM heat exchangers were fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion were investigated. This paper presents an overview of the results of this investigation from the past three years.

Experimental Investigation of Ice Phase Change Material Heat Exchangers

NASA Technical Reports Server (NTRS)

Leimkuehler, Thomas O.; Stephan, Ryan A.

2012-01-01

Phase change materials (PCM) may be useful for spacecraft thermal control systems that involve cyclical heat loads or cyclical thermal environments. Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. This can result in a decreased turndown ratio for the radiator and a reduced system mass. The use of water as a PCM rather than the more traditional paraffin wax has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. A number of ice PCM heat exchangers were fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion were investigated. This paper presents an overview of the results of this investigation from the past three years.

[Nephro-urological monitoring technology based on radionuclide functional tests (tasks of an automated workplace)].

PubMed

Averinova, S G; Kashkadaeva, A V; Shiriaev, S V; Nechipaĭ, A M; Dmitrieva, G D

1999-01-01

The paper deals with a diagnostic informational and analytical system (DIAS). The system is based on the current concept of a dynamic model of nephro-urological clearance macroregulation under retention factors at the pre-, intra-, and postrenal levels during drug load tests. DIAS includes a package of dynamic renoscintigraphic techniques, as well as original software support. A system for parameters of renal clearance regulation has been developed, which is effective at nephro-urological screening and monitoring at all treatment stages for cancer patients. A two-detector chamber which permits the mounting of a detector at an angle to the patient's body is the optimum diagnostic apparatus for a cancer clinic. The use of functional tests makes it possible to examine the regulatory reserves for each kidney, followed up by the choice of adequate corrective measures to prevent renal failure during treatment. In some cases, DIAS monitoring frequently shows a higher sensitivity to the signs of latent renal failure than does routine clinical and laboratory monitoring. The effective radiation dose taken by a patient during a study by the DIAS technology aimed at reducing radioopaque doses is 100-150 times higher than that at an X-ray study and is an order less than during routine urinary tests.

The Impact of Juvenile Coxsackievirus Infection on Cardiac Progenitor Cells and Postnatal Heart Development

PubMed Central

Sin, Jon; Puccini, Jenna M.; Huang, Chengqun; Konstandin, Mathias H.; Gilbert, Paul E.; Sussman, Mark A.; Gottlieb, Roberta A.; Feuer, Ralph

2014-01-01

Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load. PMID:25079373

Sensitivity of Latent Heating Profiles to Environmental Conditions: Implications for TRMM and Climate Research

NASA Technical Reports Server (NTRS)

Shepherd, J. Marshall; Einaudi, Franco (Technical Monitor)

2000-01-01

The Tropical Rainfall Measuring Mission (TRMM) as a part of NASA's Earth System Enterprise is the first mission dedicated to measuring tropical rainfall through microwave and visible sensors, and includes the first spaceborne rain radar. Tropical rainfall comprises two-thirds of global rainfall. It is also the primary distributor of heat through the atmosphere's circulation. It is this circulation that defines Earth's weather and climate. Understanding rainfall and its variability is crucial to understanding and predicting global climate change. Weather and climate models need an accurate assessment of the latent heating released as tropical rainfall occurs. Currently, cloud model-based algorithms are used to derive latent heating based on rainfall structure. Ultimately, these algorithms can be applied to actual data from TRMM. This study investigates key underlying assumptions used in developing the latent heating algorithms. For example, the standard algorithm is highly dependent on a system's rainfall amount and structure. It also depends on an a priori database of model-derived latent heating profiles based on the aforementioned rainfall characteristics. Unanswered questions remain concerning the sensitivity of latent heating profiles to environmental conditions (both thermodynamic and kinematic), regionality, and seasonality. This study investigates and quantifies such sensitivities and seeks to determine the optimal latent heating profile database based on the results. Ultimately, the study seeks to produce an optimized latent heating algorithm based not only on rainfall structure but also hydrometeor profiles.

[Estimation of the asymptomatic latent period of alveolar hydatidosis in patients infected in foreign endemic areas].

PubMed

Doi, Rikuo

2007-03-01

Alveolar hydatidosis (AH) is a parasitic disease with an extremely long latent period which has an important role in the endemic of human AH. The individual and average latent periods of human AH were estimated from the case histories of 19 male patients who were infected in foreign endemic areas and diagnosed surgically and pathologically as having AH after returning to Honshu, mainland of Japan. The beginning (A) and the end (C) of stay in foreign endemic areas of AH, and the midpoint (B) between (A) and (C), the time of onset of symptoms (D) and death (E) of AH were determined in the case reports. The period (D-B) from the midpoint (B) to the onset of symptoms (D) was considered as an individual latent period of AH, and the average latent period was estimated from D-B periods. The individual latent periods ranged from 3 to 44 years, and the average was 20 +/- 10 (mean +/- SD) years in the 19 cases. The average latent period was longer in 7 surviving cases (26 +/- 12) than in 12 fatal cases (16 +/- 7) at the publication of the case reports, but there was no statistically significant difference between them. The estimated latent period in this report was very close to that by Doi et al. (2000), and the traditional 5-15 years should be changed to 7-35 years.

Providing detailed information about latent tuberculosis and compliance with the PPD test among healthcare workers in Israel: a randomized controlled study.

PubMed

Taubman, Danielle; Titler, Nava; Edelstein, Hana; Elias, Mazen; Saliba, Walid

2013-12-01

The compliance of screening for latent tuberculosis (TB) with the tuberculin purified protein derivative (PPD) test is very low among healthcare workers (HCWs) in Israel. This randomized controlled study uses the Health Belief Model (HBM) as a conceptual framework to examine whether providing more information about latent TB and the PPD test increases the response rate for PPD screening among HCWs. All candidate HCWs for latent TB screening were randomly allocated to one of the following two invitations to perform the PPD test: regular letter (control group, n=97), and a letter with information about latent TB and the PPD test (intervention group, n=196). 293 HCWs were included (185 nurses, and 108 physicians). Overall, 36 (12.3%) HCWs were compliant with the PPD test screening. Compliance with PPD testing in the intervention group was not statistically different from the control group, RR 0.87 (95% CI, 0.46-1.65). Compliance for latent TB screening is low among HCWs in northeastern Israel. Providing detailed information about latent TB was not associated with increased test compliance. Understanding existing disparities in screening rates and potential barriers to latent TB screening among HCWs is important in order to move forward and successfully increase screening rates. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Evidence of Associations between Cytokine Genes and Subjective Reports of Sleep Disturbance in Oncology Patients and Their Family Caregivers

PubMed Central

Miaskowski, Christine; Cooper, Bruce A.; Dhruva, Anand; Dunn, Laura B.; Langford, Dale J.; Cataldo, Janine K.; Baggott, Christina R.; Merriman, John D.; Dodd, Marylin; Lee, Kathryn; West, Claudia; Paul, Steven M.; Aouizerat, Bradley E.

2012-01-01

The purposes of this study were to identify distinct latent classes of individuals based on subjective reports of sleep disturbance; to examine differences in demographic, clinical, and symptom characteristics between the latent classes; and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on General Sleep Disturbance Scale (GSDS) obtained prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in candidate cytokine genes were interrogated for differences between the two latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on GSDS group membership. Two latent classes were identified: lower sleep disturbance (88.5%) and higher sleep disturbance (11.5%). Participants who were younger and had a lower Karnofsky Performance status score were more likely to be in the higher sleep disturbance class. Variation in two cytokine genes (i.e., IL6, NFKB) predicted latent class membership. Evidence was found for latent classes with distinct sleep disturbance trajectories. Unique genetic markers in cytokine genes may partially explain the interindividual heterogeneity characterizing these trajectories. PMID:22844404

Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival

PubMed Central

Sanchez, Erica L.; Carroll, Patrick A.; Thalhofer, Angel B.; Lagunoff, Michael

2015-01-01

Kaposi’s Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of Kaposi’s Sarcoma (KS). KSHV establishes a predominantly latent infection in the main KS tumor cell type, the spindle cell, which is of endothelial cell origin. KSHV requires the induction of multiple metabolic pathways, including glycolysis and fatty acid synthesis, for the survival of latently infected endothelial cells. Here we demonstrate that latent KSHV infection leads to increased levels of intracellular glutamine and enhanced glutamine uptake. Depletion of glutamine from the culture media leads to a significant increase in apoptotic cell death in latently infected endothelial cells, but not in their mock-infected counterparts. In cancer cells, glutamine is often required for glutaminolysis to provide intermediates for the tri-carboxylic acid (TCA) cycle and support for the production of biosynthetic and bioenergetic precursors. In the absence of glutamine, the TCA cycle intermediates alpha-ketoglutarate (αKG) and pyruvate prevent the death of latently infected cells. Targeted drug inhibition of glutaminolysis also induces increased cell death in latently infected cells. KSHV infection of endothelial cells induces protein expression of the glutamine transporter, SLC1A5. Chemical inhibition of SLC1A5, or knockdown by siRNA, leads to similar cell death rates as glutamine deprivation and, similarly, can be rescued by αKG. KSHV also induces expression of the heterodimeric transcription factors c-Myc-Max and related heterodimer MondoA-Mlx. Knockdown of MondoA inhibits expression of both Mlx and SLC1A5 and induces a significant increase in cell death of only cells latently infected with KSHV, again, fully rescued by the supplementation of αKG. Therefore, during latent infection of endothelial cells, KSHV activates and requires the Myc/MondoA-network to upregulate the glutamine transporter, SLC1A5, leading to increased glutamine uptake for glutaminolysis. These findings expand our understanding of the required metabolic pathways that are activated during latent KSHV infection of endothelial cells, and demonstrate a novel role for the extended Myc-regulatory network, specifically MondoA, during latent KSHV infection. PMID:26197457

Dynamic Latent Trait Models with Mixed Hidden Markov Structure for Mixed Longitudinal Outcomes.

PubMed

Zhang, Yue; Berhane, Kiros

2016-01-01

We propose a general Bayesian joint modeling approach to model mixed longitudinal outcomes from the exponential family for taking into account any differential misclassification that may exist among categorical outcomes. Under this framework, outcomes observed without measurement error are related to latent trait variables through generalized linear mixed effect models. The misclassified outcomes are related to the latent class variables, which represent unobserved real states, using mixed hidden Markov models (MHMM). In addition to enabling the estimation of parameters in prevalence, transition and misclassification probabilities, MHMMs capture cluster level heterogeneity. A transition modeling structure allows the latent trait and latent class variables to depend on observed predictors at the same time period and also on latent trait and latent class variables at previous time periods for each individual. Simulation studies are conducted to make comparisons with traditional models in order to illustrate the gains from the proposed approach. The new approach is applied to data from the Southern California Children Health Study (CHS) to jointly model questionnaire based asthma state and multiple lung function measurements in order to gain better insight about the underlying biological mechanism that governs the inter-relationship between asthma state and lung function development.

Adolescent cigarette smoking: health-related behavior or normative transgression?

PubMed

Turbin, M S; Jessor, R; Costa, F M

2000-09-01

Relations among measures of adolescent behavior were examined to determine whether cigarette smoking fits into a structure of problem behaviors-behaviors that involve normative transgression-or a structure of health-related behaviors, or both. In an ethnically and socioeconomically diverse sample of 1782 male and female high school adolescents, four first-order problem behavior latent variables-sexual intercourse experience, alcohol abuse, illicit drug use, and delinquency-were established and together were shown to reflect a second-order latent variable of problem behavior. Four first-order latent variables of health-related behaviors-unhealthy dietary habits, sedentary behavior, unsafe behavior, and poor dental hygiene-were also established and together were shown to reflect a second-order latent variable of health-compromising behavior. The structure of relations among those latent variables was modeled. Cigarette smoking had a significant and substantial loading only on the problem-behavior latent variable; its loading on the health-compromising behavior latent variable was essentially zero. Adolescent cigarette smoking relates strongly and directly to problem behaviors and only indirectly, if at all, to health-compromising behaviors. Interventions to prevent or reduce adolescent smoking should attend more to factors that influence problem behaviors.

A Taxonomy of Latent Structure Assumptions for Probability Matrix Decomposition Models.

ERIC Educational Resources Information Center

Meulders, Michel; De Boeck, Paul; Van Mechelen, Iven

2003-01-01

Proposed a taxonomy of latent structure assumptions for probability matrix decomposition (PMD) that includes the original PMD model and a three-way extension of the multiple classification latent class model. Simulation study results show the usefulness of the taxonomy. (SLD)

Understanding Latent Tuberculosis: A Moving Target

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2012-01-01

Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be ~2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease. PMID:20562268

A Latent Heat Retrieval and its Effects on the Intensity and Structure Change of Hurricane Guillermo (1997). Part I: The Algorithm and Observations.

NASA Technical Reports Server (NTRS)

Guimond, Stephen R.; Bourassa, mark A.; Reasor, Paul D.

2011-01-01

The release of latent heat in clouds is an essential part of the formation and I intensification ohurricanes. The community knows very little about the intensity and structure of latent heating due largely to inadequate observations. In this paper, a new method for retrieving the latent heating field in hurricanes from airborne Dopple radar is presented and fields from rapidly intensifying Hurricane Guillermo (1997) are shown.

Extraction of latent images from printed media

NASA Astrophysics Data System (ADS)

Sergeyev, Vladislav; Fedoseev, Victor

2015-12-01

In this paper we propose an automatic technology for extraction of latent images from printed media such as documents, banknotes, financial securities, etc. This technology includes image processing by adaptively constructed Gabor filter bank for obtaining feature images, as well as subsequent stages of feature selection, grouping and multicomponent segmentation. The main advantage of the proposed technique is versatility: it allows to extract latent images made by different texture variations. Experimental results showing performance of the method over another known system for latent image extraction are given.

A Retrieval of Tropical Latent Heating Using the 3D Structure of Precipitation Features

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

Ahmed, Fiaz; Schumacher, Courtney; Feng, Zhe

Traditionally, radar-based latent heating retrievals use rainfall to estimate the total column-integrated latent heating and then distribute that heating in the vertical using a model-based look-up table (LUT). In this study, we develop a new method that uses size characteristics of radar-observed precipitating echo (i.e., area and mean echo-top height) to estimate the vertical structure of latent heating. This technique (named the Convective-Stratiform Area [CSA] algorithm) builds on the fact that the shape and magnitude of latent heating profiles are dependent on the organization of convective systems and aims to avoid some of the pitfalls involved in retrieving accurate rainfallmore » amounts and microphysical information from radars and models. The CSA LUTs are based on a high-resolution Weather Research and Forecasting model (WRF) simulation whose domain spans much of the near-equatorial Indian Ocean. When applied to S-PolKa radar observations collected during the DYNAMO/CINDY2011/AMIE field campaign, the CSA retrieval compares well to heating profiles from a sounding-based budget analysis and improves upon a simple rain-based latent heating retrieval. The CSA LUTs also highlight the fact that convective latent heating increases in magnitude and height as cluster area and echo-top heights grow, with a notable congestus signature of cooling at mid levels. Stratiform latent heating is less dependent on echo-top height, but is strongly linked to area. Unrealistic latent heating profiles in the stratiform LUT, viz., a low-level heating spike, an elevated melting layer, and net column cooling were identified and corrected for. These issues highlight the need for improvement in model parameterizations, particularly in linking microphysical phase changes to larger mesoscale processes.« less

Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-β

PubMed Central

Alcaraz, Lindsay B.; Exposito, Jean-Yves; Chuvin, Nicolas; Pommier, Roxane M.; Cluzel, Caroline; Martel, Sylvie; Sentis, Stéphanie; Bartholin, Laurent; Lethias, Claire

2014-01-01

Transforming growth factor β (TGF-β) isoforms are secreted as inactive complexes formed through noncovalent interactions between the bioactive TGF-β entity and its N-terminal latency-associated peptide prodomain. Extracellular activation of the latent TGF-β complex is a crucial step in the regulation of TGF-β function for tissue homeostasis. We show that the fibrinogen-like (FBG) domain of the matrix glycoprotein tenascin-X (TNX) interacts physically with the small latent TGF-β complex in vitro and in vivo, thus regulating the bioavailability of mature TGF-β to cells by activating the latent cytokine into an active molecule. Activation by the FBG domain most likely occurs through a conformational change in the latent complex and involves a novel cell adhesion–dependent mechanism. We identify α11β1 integrin as a cell surface receptor for TNX and show that this integrin is crucial to elicit FBG-mediated activation of latent TGF-β and subsequent epithelial-to-mesenchymal transition in mammary epithelial cells. PMID:24821840

Modulation of immunity in mice with latent toxoplasmosis--the experimental support for the immunosuppression hypothesis of Toxoplasma-induced changes in reproduction of mice and humans.

PubMed

Kaňková, Sárka; Holáň, Vladimír; Zajícová, Alena; Kodym, Petr; Flegr, Jaroslav

2010-11-01

The immunosuppression hypothesis suggests that the increased sex ratio in mice and women with latent toxoplasmosis, retarded embryonic growth in the early phases of pregnancy, prolonged pregnancy of Toxoplasma-infected women, and increased prevalence of toxoplasmosis in mothers of children with Down syndrome can be explained by the presumed immunosuppressive effects of latent toxoplasmosis. Here, we searched for indices of immunosuppression in mice experimentally infected with Toxoplasma gondii. Our results showed that mice in the early phase of latent infection exhibited temporarily increased production of interleukin (IL)-12 and decreased production of IL-10. In accordance with the immunosuppression hypothesis, the mice showed decreased production of IL-2 and nitric oxide and decreased proliferation reaction (synthesis of DNA) in the mixed lymphocyte culture in the early and also in the late phases of latent toxoplasmosis. Since about 30% of the world population are latently infected by T. gondii, the toxoplasmosis-associated immunosuppression might have serious public health consequences.

Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

PubMed Central

Krishna, B. A.; Spiess, K.; Poole, E. L.; Lau, B.; Voigt, S.; Kledal, T. N.; Rosenkilde, M. M.; Sinclair, J. H.

2017-01-01

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation. PMID:28148951

Feature extraction for document text using Latent Dirichlet Allocation

NASA Astrophysics Data System (ADS)

Prihatini, P. M.; Suryawan, I. K.; Mandia, IN

2018-01-01

Feature extraction is one of stages in the information retrieval system that used to extract the unique feature values of a text document. The process of feature extraction can be done by several methods, one of which is Latent Dirichlet Allocation. However, researches related to text feature extraction using Latent Dirichlet Allocation method are rarely found for Indonesian text. Therefore, through this research, a text feature extraction will be implemented for Indonesian text. The research method consists of data acquisition, text pre-processing, initialization, topic sampling and evaluation. The evaluation is done by comparing Precision, Recall and F-Measure value between Latent Dirichlet Allocation and Term Frequency Inverse Document Frequency KMeans which commonly used for feature extraction. The evaluation results show that Precision, Recall and F-Measure value of Latent Dirichlet Allocation method is higher than Term Frequency Inverse Document Frequency KMeans method. This shows that Latent Dirichlet Allocation method is able to extract features and cluster Indonesian text better than Term Frequency Inverse Document Frequency KMeans method.

Forensic Discrimination of Latent Fingerprints Using Laser-Induced Breakdown Spectroscopy (LIBS) and Chemometric Approaches.

PubMed

Yang, Jun-Ho; Yoh, Jack J

2018-01-01

A novel technique is reported for separating overlapping latent fingerprints using chemometric approaches that combine laser-induced breakdown spectroscopy (LIBS) and multivariate analysis. The LIBS technique provides the capability of real time analysis and high frequency scanning as well as the data regarding the chemical composition of overlapping latent fingerprints. These spectra offer valuable information for the classification and reconstruction of overlapping latent fingerprints by implementing appropriate statistical multivariate analysis. The current study employs principal component analysis and partial least square methods for the classification of latent fingerprints from the LIBS spectra. This technique was successfully demonstrated through a classification study of four distinct latent fingerprints using classification methods such as soft independent modeling of class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA). The novel method yielded an accuracy of more than 85% and was proven to be sufficiently robust. Furthermore, through laser scanning analysis at a spatial interval of 125 µm, the overlapping fingerprints were reconstructed as separate two-dimensional forms.

Evidence for the Continuous Latent Structure of Mania in the Epidemiologic Catchment Area from Multiple Latent Structure and Construct Validation Methodologies

PubMed Central

Prisciandaro, James J.; Roberts, John E.

2011-01-01

Background Although psychiatric diagnostic systems have conceptualized mania as a discrete phenomenon, appropriate latent structure investigations testing this conceptualization are lacking. In contrast to these diagnostic systems, several influential theories of mania have suggested a continuous conceptualization. The present study examined whether mania has a continuous or discrete latent structure using a comprehensive approach including taxometric, information-theoretic latent distribution modeling (ITLDM), and predictive validity methodologies in the Epidemiologic Catchment Area (ECA) study. Methods Eight dichotomous manic symptom items were submitted to a variety of latent structural analyses; including factor analyses, taxometric procedures, and ITLDM; in 10,105 ECA community participants. Additionally, a variety of continuous and discrete models of mania were compared in terms of their relative abilities to predict outcomes (i.e., health service utilization, internalizing and externalizing disorders, and suicidal behavior). Results Taxometric and ITLDM analyses consistently supported a continuous conceptualization of mania. In ITLDM analyses, a continuous model of mania demonstrated 6:52:1 odds over the best fitting latent class model of mania. Factor analyses suggested that the continuous structure of mania was best represented by a single latent factor. Predictive validity analyses demonstrated a consistent superior ability of continuous models of mania relative to discrete models. Conclusions The present study provided three independent lines of support for a continuous conceptualization of mania. The implications of a continuous model of mania are discussed. PMID:20507671

Prevalence and risk factors for latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique.

PubMed

Belo, Celso; Naidoo, Saloshni

2017-06-08

Healthcare workers in high tuberculosis burdened countries are occupationally exposed to the tuberculosis disease with uncomplicated and complicated tuberculosis on the increase among them. Most of them acquire Mycobacterium tuberculosis but do not progress to the active disease - latent tuberculosis infection. The objective of this study was to assess the prevalence and risk factors associated with latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique. This cross-sectional study of healthcare workers was conducted between 2014 and 2015. Participants (n = 209) were administered a questionnaire on demographics and occupational tuberculosis exposure and had a tuberculin skin test administered. Multivariate linear and logistic regression tested for associations between independent variables and dependent outcomes (tuberculin skin test induration and latent tuberculosis infection status). The prevalence of latent tuberculosis infection was 34.4%. Latent tuberculosis infection was highest in those working for more than eight years (39.3%), those who had no BCG vaccination (39.6%) and were immunocompromised (78.1%). Being immunocompromised was significantly associated with latent tuberculosis infection (OR 5.97 [95% CI 1.89; 18.87]). Positive but non-significant associations occurred with working in the medical domain (OR 1.02 [95% CI 0.17; 6.37]), length of employment > eight years (OR 1.97 [95% CI 0.70; 5.53]) and occupational contact with tuberculosis patients (OR 1.24 [95% CI 0.47; 3.27]). Personal and occupational factors were positively associated with latent tuberculosis infection among healthcare workers in Mozambique.

Ellipsometry-like analysis of polarization state for micro cracks using stress-induced light scattering method

NASA Astrophysics Data System (ADS)

Sakata, Yoshitaro; Terasaki, Nao; Sakai, Kazufumi; Nonaka, Kazuhiro

2016-03-01

Fine polishing techniques, such as chemical mechanical polishing (CMP), are important to glass substrate manufacturing. When these techniques involve mechanical interaction in the form of friction between the abrasive and the substrate surface during polishing, latent flaws may form on the product. Fine polishing induced latent flaws in glass substrates may become obvious during a subsequent cleaning process if the glass surface is eroded away by chemical interaction with a cleaning liquid. Thus, latent flaws reduce product yield. A novel technique (the stress-induced light scattering method; SILSM) which was combined with light scattering method and stress effects was proposed for inspecting surface to detect polishing induced latent flaws. This method is able to distinguish between latent flaws and tiny particles on the surface. In this method, an actuator deforms a sample inducing stress effects around the tip of a latent flaw caused by the deformation, which in turn changes the refractive index of the material around the tip of the latent flaw because of the photoelastic effect. A CCD camera detects this changed refractive index as variations in light-scattering intensity. In this study, the changes in reflection coefficients and polarization states after application of stress to a glass substrate were calculated and evaluated qualitatively using Jones matrix-like ellipsometry. As the results, it was shown that change in the polarization states around the tip of latent flaw were evaluated between before and after applied stress, qualitatively.

Latent structure modeling underlying theophylline tablet formulations using a Bayesian network based on a self-organizing map clustering.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2015-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and design space. In this article, we integrate thin-plate spline (TPS) interpolation, Kohonen's self-organizing map (SOM) and a Bayesian network (BN) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared using a standard formulation. We measured the tensile strength and disintegration time as response variables and the compressibility, cohesion and dispersibility of the pretableting blend as latent variables. We predicted these variables quantitatively using nonlinear TPS, generated a large amount of data on pretableting blends and tablets and clustered these data into several clusters using a SOM. Our results show that we are able to predict the experimental values of the latent and response variables with a high degree of accuracy and are able to classify the tablet data into several distinct clusters. In addition, to visualize the latent structure between the causal and latent factors and the response variables, we applied a BN method to the SOM clustering results. We found that despite having inserted latent variables between the causal factors and response variables, their relation is equivalent to the results for the SOM clustering, and thus we are able to explain the underlying latent structure. Consequently, this technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulation.

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

PubMed Central

Medstrand, Patrik; Yilmaz, Aylin; Isberg, Per-Erik; Gisslén, Magnus; Björkman, Per

2017-01-01

Objective Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART. Methods HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50–199 copies/mL, LLV 200–999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner. Results LLV 50–199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200–999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200–999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41–7.03, p<0.01]), whereas LLV 50–199 copies/mL was not (1.01 [0.34–4.31, p = 0.99]; median follow-up 4.5 years). LLV 200–999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98–5.32, p = 0.05) and LLV 50–199 copies/mL of 2.19 (0.90–5.37, p = 0.09). Conclusions In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200–999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis. PMID:28683128

Longitudinal Models of Reliability and Validity: A Latent Curve Approach.

ERIC Educational Resources Information Center

Tisak, John; Tisak, Marie S.

1996-01-01

Dynamic generalizations of reliability and validity that will incorporate longitudinal or developmental models, using latent curve analysis, are discussed. A latent curve model formulated to depict change is incorporated into the classical definitions of reliability and validity. The approach is illustrated with sociological and psychological…

Surgical Adverse Events, Risk Management, and Malpractice Outcome: Morbidity and Mortality Review Is Not Enough

PubMed Central

Morris, John A.; Carrillo, Ysela; Jenkins, Judith M.; Smith, Philip W.; Bledsoe, Sandy; Pichert, James; White, Andrew

2003-01-01

Objective To review all admissions (age > 13) to three surgical patient care centers at a single academic medical center between January 1, 1995, and December 6, 1999, for significant surgical adverse events. Summary Background Data Little data exist on the interrelationships between surgical adverse events, risk management, malpractice claims, and resulting indemnity payments to plaintiffs. The authors hypothesized that examination of this process would identify performance improvement opportunities overlooked by standard medical peer review; the risk of litigation would be constant across the three homogeneous patient care centers; and the risk management process would exceed the performance improvement process. Methods Data collected included patient demographics (age, gender, and employment status), hospital financials (hospital charges, costs, and financial class), and outcome. Outcome categories were medical (disability: <1 month, 1–6 months, permanent/death), legal (no legal action, settlement, summary judgment), financial (indemnity payments, legal fees, write-offs), and cause and effect analysis. Cause and effect analysis attempts to identify system failures contributing to adverse outcomes. This was determined by two independent analysts using the 17 Harvard criteria and subdividing these into subsystem causative factors. Results The study group consisted of 130 patients with surgical adverse events resulting in total liabilities of $8.2 million. The incidence of adverse events per 1,000 admissions across the three patient care centers was similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30, women’s health = $90, trauma = $520). Patient demographics were not predictive of high-risk subgroups for adverse events or litigation. In terms of medical outcome, 51 patients had permanent disability or death, accounting for 98% of the indemnity payments. In terms of legal outcome, 103 patients received no indemnity payments, 15 patients received indemnity payments, four suits remain open, and in eight cases charges were written off ($0.121 million). To date, no cases have been adjudicated in court. Cause and effect analysis identified 390 system failures contributing to the adverse events (mean 3.0 failures per adverse event); there were 4.7 failures per adverse event in the 15 indemnity cases. Five categories of causes accounted for 75% of the failures (patient management, n = 104; communication, n = 89; administration, n = 33; documentation, n = 32; behavior, n = 23). The current medical review process would have identified 104 of 390 systems failures (37%). Conclusions This study demonstrates no rational link between the tort system and the reduction of adverse events. Sixty-three percent of contributing causes to adverse events were undetected by current medical review processes. Adverse events occur at the interface between different systems or disciplines and result from multiple failures. Indemnity costs per hospital day vary dramatically by patient care center (range $3.60–97.60 a day). The regionalization of healthcare is in jeopardy from the burden of high indemnity payments. PMID:12796581

Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

PubMed

Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

2016-01-01

The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA < 50 copies/ml, median CD4 540 cells/μl) were included. Mean self-reported adherence (on a 0-100 visual analogue scale) was 80% (standard deviation, 18.7). Drug concentration was subtherapeutic in 16 patients (12.3%), of which 7 (5.4%) had undetectable drug levels (< 0.05 mg/L). Of these last seven patients, five (71.4%) reported an adherence below 80%. In a multivariable analysis, females and patients with undetectable drug levels (mean change -18.43%, 95% confidence intervals (CIs) -31.83 to -5.03, p = 0.007) showed a lower self-reported adherence, while those with HIV RNA < 50 copies/ml showed a higher adherence. Lower self-reported adherence (odds ratio 0.62 per 10% increase, 95% CI = 0.43-0.89, p = 0.009) and longer time from last drug intake were independently related to the development of undetectable drug levels. We also found that a higher symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

PubMed

Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

2015-04-01

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Gonorrhea in homosexual men.

PubMed Central

Austin, T. W.; Lent, B.; Pattison, F. L.

1978-01-01

Extragenital gonorrhea was seen in 65% of 54 cases of gonorrhea in 43 homosexual men attending a venereal diseases clinic between 1974 and 1977; in 21 cases the infection was extragenital only. This type of gonorrhea was often asymptomatic and was associated with a high rate of failure of initial treatment in 6 of the 50 cases in which the patient returned for follow-up assessment, and in 5 of the 6 the persistent infection was extragenital. Syphillis was seen concomitantly or had previously occurred in 6 of the 54 cases. Fifteen of 28 cases of primary, secondary or early latent syphilis seen in men during the same study period had occurred in homosexuals. Appropriate testing for extragenital gonorrhea and for syphilis is important in homosexual men who present for examination, and homosexuality with the possibility of extragenital gonorrhea should be considered in a man with syphilis of recent onset. PMID:709473

Gonorrhea in homosexual men.

PubMed

Austin, T W; Lent, B; Pattison, F L

1978-10-07

Extragenital gonorrhea was seen in 65% of 54 cases of gonorrhea in 43 homosexual men attending a venereal diseases clinic between 1974 and 1977; in 21 cases the infection was extragenital only. This type of gonorrhea was often asymptomatic and was associated with a high rate of failure of initial treatment in 6 of the 50 cases in which the patient returned for follow-up assessment, and in 5 of the 6 the persistent infection was extragenital. Syphillis was seen concomitantly or had previously occurred in 6 of the 54 cases. Fifteen of 28 cases of primary, secondary or early latent syphilis seen in men during the same study period had occurred in homosexuals. Appropriate testing for extragenital gonorrhea and for syphilis is important in homosexual men who present for examination, and homosexuality with the possibility of extragenital gonorrhea should be considered in a man with syphilis of recent onset.

Specification, testing, and interpretation of gene-by-measured-environment interaction models in the presence of gene-environment correlation

PubMed Central

Rathouz, Paul J.; Van Hulle, Carol A.; Lee Rodgers, Joseph; Waldman, Irwin D.; Lahey, Benjamin B.

2009-01-01

Purcell (2002) proposed a bivariate biometric model for testing and quantifying the interaction between latent genetic influences and measured environments in the presence of gene-environment correlation. Purcell’s model extends the Cholesky model to include gene-environment interaction. We examine a number of closely-related alternative models that do not involve gene-environment interaction but which may fit the data as well Purcell’s model. Because failure to consider these alternatives could lead to spurious detection of gene-environment interaction, we propose alternative models for testing gene-environment interaction in the presence of gene-environment correlation, including one based on the correlated factors model. In addition, we note mathematical errors in the calculation of effect size via variance components in Purcell’s model. We propose a statistical method for deriving and interpreting variance decompositions that are true to the fitted model. PMID:18293078

Living with hypertrophic cardiomyopathy and an implantable defibrillator.

PubMed

Magnusson, Peter; Jonsson, Jessica; Mörner, Stellan; Fredriksson, Lennart

2017-05-10

ICDs efficiently terminate life-threatening arrhythmias, but complications occur during long-term follow-up. Patients' own perspective is largely unknown. The aim of the study was to describe experiences of hypertrophic cardiomyopathy (HCM) patients with implantable defibrillators (ICDs). We analyzed 26 Swedish patient interviews using hermeneutics and latent content analysis. Patients (aged 27-76 years) were limited by HCM especially if it deteriorates into heart failure. The ICD implies safety, gratitude, and is accepted as a part of the body even when inappropriate ICD shocks are encountered. Nobody regretted the implant. Both the disease and the ICD affected professional life and leisure time activities, especially at younger ages. Family support was usually strong, but sometimes resulted in overprotection, whereas health care focused on medical issues. Despite limitations, patients adapted, accepted, and managed challenges. HCM patients with ICDs reported good spirit and hope even though they had to adapt and accept limitations over time.

On the relation between orbital-localization and self-interaction errors in the density functional theory treatment of organic semiconductors.

PubMed

Körzdörfer, T

2011-03-07

It is commonly argued that the self-interaction error (SIE) inherent in semilocal density functionals is related to the degree of the electronic localization. Yet at the same time there exists a latent ambiguity in the definitions of the terms "localization" and "self-interaction," which ultimately prevents a clear and readily accessible quantification of this relationship. This problem is particularly pressing for organic semiconductor molecules, in which delocalized molecular orbitals typically alternate with localized ones, thus leading to major distortions in the eigenvalue spectra. This paper discusses the relation between localization and SIEs in organic semiconductors in detail. Its findings provide further insights into the SIE in the orbital energies and yield a new perspective on the failure of self-interaction corrections that identify delocalized orbital densities with electrons. © 2011 American Institute of Physics.

Multilevel Higher-Order Item Response Theory Models

ERIC Educational Resources Information Center

Huang, Hung-Yu; Wang, Wen-Chung

2014-01-01

In the social sciences, latent traits often have a hierarchical structure, and data can be sampled from multiple levels. Both hierarchical latent traits and multilevel data can occur simultaneously. In this study, we developed a general class of item response theory models to accommodate both hierarchical latent traits and multilevel data. The…

A Framework for Multifaceted Evaluation of Student Models

ERIC Educational Resources Information Center

Huang, Yun; González-Brenes, José P.; Kumar, Rohit; Brusilovsky, Peter

2015-01-01

Latent variable models, such as the popular Knowledge Tracing method, are often used to enable adaptive tutoring systems to personalize education. However, finding optimal model parameters is usually a difficult non-convex optimization problem when considering latent variable models. Prior work has reported that latent variable models obtained…

The Latent Variable Approach as Applied to Transitive Reasoning

ERIC Educational Resources Information Center

Bouwmeester, Samantha; Vermunt, Jeroen K.; Sijtsma, Klaas

2012-01-01

We discuss the limitations of hypothesis testing using (quasi-) experiments in the study of cognitive development and suggest latent variable modeling as a viable alternative to experimentation. Latent variable models allow testing a theory as a whole, incorporating individual differences with respect to developmental processes or abilities in the…

Much Ado about Nothing--Or at Best, Very Little

ERIC Educational Resources Information Center

Widaman, Keith F.

2014-01-01

Latent variable structural equation modeling has become the analytic method of choice in many domains of research in psychology and allied social sciences. One important aspect of a latent variable model concerns the relations hypothesized to hold between latent variables and their indicators. The most common specification of structural equation…

Testing Specific Hypotheses Concerning Latent Group Differences in Multi-group Covariance Structure Analysis with Structured Means.

ERIC Educational Resources Information Center

Dolan, Conor V.; Molenaar, Peter C. M.

1994-01-01

In multigroup covariance structure analysis with structured means, the traditional latent selection model is formulated as a special case of phenotypic selection. Illustrations with real and simulated data demonstrate how one can test specific hypotheses concerning selection on latent variables. (SLD)

Nonlinear and Quasi-Simplex Patterns in Latent Growth Models

ERIC Educational Resources Information Center

Bianconcini, Silvia

2012-01-01

In the SEM literature, simplex and latent growth models have always been considered competing approaches for the analysis of longitudinal data, even if they are strongly connected and both of specific importance. General dynamic models, which simultaneously estimate autoregressive structures and latent curves, have been recently proposed in the…

A Latent Class Approach to Fitting the Weighted Euclidean Model, CLASCAL.

ERIC Educational Resources Information Center

Winsberg, Suzanne; De Soete, Geert

1993-01-01

A weighted Euclidean distance model is proposed that incorporates a latent class approach (CLASCAL). The contribution to the distance function between two stimuli is per dimension weighted identically by all subjects in the same latent class. A model selection strategy is proposed and illustrated. (SLD)

Confidence Intervals for a Semiparametric Approach to Modeling Nonlinear Relations among Latent Variables

ERIC Educational Resources Information Center

Pek, Jolynn; Losardo, Diane; Bauer, Daniel J.

2011-01-01

Compared to parametric models, nonparametric and semiparametric approaches to modeling nonlinearity between latent variables have the advantage of recovering global relationships of unknown functional form. Bauer (2005) proposed an indirect application of finite mixtures of structural equation models where latent components are estimated in the…

Estimating Latent Variable Interactions with Nonnormal Observed Data: A Comparison of Four Approaches

ERIC Educational Resources Information Center

Cham, Heining; West, Stephen G.; Ma, Yue; Aiken, Leona S.

2012-01-01

A Monte Carlo simulation was conducted to investigate the robustness of 4 latent variable interaction modeling approaches (Constrained Product Indicator [CPI], Generalized Appended Product Indicator [GAPI], Unconstrained Product Indicator [UPI], and Latent Moderated Structural Equations [LMS]) under high degrees of nonnormality of the observed…

Spurious Latent Classes in the Mixture Rasch Model

ERIC Educational Resources Information Center

Alexeev, Natalia; Templin, Jonathan; Cohen, Allan S.

2011-01-01

Mixture Rasch models have been used to study a number of psychometric issues such as goodness of fit, response strategy differences, strategy shifts, and multidimensionality. Although these models offer the potential for improving understanding of the latent variables being measured, under some conditions overextraction of latent classes may…

A Composite Likelihood Inference in Latent Variable Models for Ordinal Longitudinal Responses

ERIC Educational Resources Information Center

Vasdekis, Vassilis G. S.; Cagnone, Silvia; Moustaki, Irini

2012-01-01

The paper proposes a composite likelihood estimation approach that uses bivariate instead of multivariate marginal probabilities for ordinal longitudinal responses using a latent variable model. The model considers time-dependent latent variables and item-specific random effects to be accountable for the interdependencies of the multivariate…

Cross-Informant Agreement on Child and Adolescent Withdrawn Behavior: A Latent Class Approach

ERIC Educational Resources Information Center

Rubin, David H.; Althoff, Robert R.; Walkup, John T.; Hudziak, James J.

2013-01-01

Withdrawn behavior (WB) relates to many developmental outcomes, including pervasive developmental disorders, anxiety, depression, psychosis, personality disorders and suicide. No study has compared the latent profiles of different informants' reports on WB. This study uses multi-informant latent class analyses (LCA) of the child behavior checklist…

A Latent Class Unfolding Model for Analyzing Single Stimulus Preference Ratings.

ERIC Educational Resources Information Center

De Soete, Geert; Heiser, Willem J.

1993-01-01

A latent class unfolding model is developed for single stimulus preference ratings. One advantage is the possibility of testing the spatial unfolding model against the unconstrained latent class model for rating data. The model is applied to data about party preferences of members of the Dutch parliament. (SLD)

A Bayesian Semiparametric Latent Variable Model for Mixed Responses

ERIC Educational Resources Information Center

Fahrmeir, Ludwig; Raach, Alexander

2007-01-01

In this paper we introduce a latent variable model (LVM) for mixed ordinal and continuous responses, where covariate effects on the continuous latent variables are modelled through a flexible semiparametric Gaussian regression model. We extend existing LVMs with the usual linear covariate effects by including nonparametric components for nonlinear…

Latent Image Processing Can Bolster the Value of Quizzes.

ERIC Educational Resources Information Center

Singer, David

1985-01-01

Latent image processing is a method which reveals hidden ink when marked with a special pen. Using multiple-choice items with commercially available latent image transfers can provide immediate feedback on take-home quizzes. Students benefitted from formative evaluation and were challenged to search for alternative solutions and explain unexpected…

The Impact of Noninvariant Intercepts in Latent Means Models

ERIC Educational Resources Information Center

Whittaker, Tiffany A.

2013-01-01

Latent means methods such as multiple-indicator multiple-cause (MIMIC) and structured means modeling (SMM) allow researchers to determine whether or not a significant difference exists between groups' factor means. Strong invariance is typically recommended when interpreting latent mean differences. The extent of the impact of noninvariant…

Piecewise Linear-Linear Latent Growth Mixture Models with Unknown Knots

ERIC Educational Resources Information Center

Kohli, Nidhi; Harring, Jeffrey R.; Hancock, Gregory R.

2013-01-01

Latent growth curve models with piecewise functions are flexible and useful analytic models for investigating individual behaviors that exhibit distinct phases of development in observed variables. As an extension of this framework, this study considers a piecewise linear-linear latent growth mixture model (LGMM) for describing segmented change of…

Research on the application of a decoupling algorithm for structure analysis

NASA Technical Reports Server (NTRS)

Denman, E. D.

1980-01-01

The mathematical theory for decoupling mth-order matrix differential equations is presented. It is shown that the decoupling precedure can be developed from the algebraic theory of matrix polynomials. The role of eigenprojectors and latent projectors in the decoupling process is discussed and the mathematical relationships between eigenvalues, eigenvectors, latent roots, and latent vectors are developed. It is shown that the eigenvectors of the companion form of a matrix contains the latent vectors as a subset. The spectral decomposition of a matrix and the application to differential equations is given.

Formation of nanometer-size wires using infiltration into latent nuclear tracks

DOEpatents

Musket, Ronald G.; Felter, Thomas E.

2002-01-01

Nanometer-size wires having a cross-sectional dimension of less than 8 nm with controllable lengths and diameters are produced by infiltrating latent nuclear or ion tracks formed in trackable materials with atomic species. The trackable materials and atomic species are essentially insoluble in each other, thus the wires are formed by thermally driven, self-assembly of the atomic species during annealing, or re-crystallization, of the damage in the latent tracks. Unlike conventional ion track lithography, the inventive method does not require etching of the latent tracks.

Eliminate background interference from latent fingerprints using ultraviolet multispectral imaging

NASA Astrophysics Data System (ADS)

Huang, Wei; Xu, Xiaojing; Wang, Guiqiang

2014-02-01

Fingerprints are the most important evidence in crime scene. The technology of developing latent fingerprints is one of the hottest research areas in forensic science. Recently, multispectral imaging which has shown great capability in fingerprints development, questioned document detection and trace evidence examination is used in detecting material evidence. This paper studied how to eliminate background interference from non-porous and porous surface latent fingerprints by rotating filter wheel ultraviolet multispectral imaging. The results approved that background interference could be removed clearly from latent fingerprints by using multispectral imaging in ultraviolet bandwidth.

Development of molecular tests for the detection of ILAR and latent viruses in fruit trees.

PubMed

Roussel, S; Kummert, J; Dutrecq, O; Lepoivre, P; Jijakli, M H

2004-01-01

The detection throughout the year of latent and ILAR viruses in fruit tress by classical serological tests appear to be unreliable. We have developed RT-PCR tests for a reliable detection of latent and ILAR viruses in fruit trees. These assays were then simplified to allow the direct use of crude plant extracts instead of total RNA preparations, and the analyses of pooled samples. In this way, such RT-PCR protocols are suitable for a routine diagnosis of latent and ILAR viruses in fruit tree certification.

Managerial performance and cost efficiency of Japanese local public hospitals: a latent class stochastic frontier model.

PubMed

Besstremyannaya, Galina

2011-09-01

The paper explores the link between managerial performance and cost efficiency of 617 Japanese general local public hospitals in 1999-2007. Treating managerial performance as unobservable heterogeneity, the paper employs a panel data stochastic cost frontier model with latent classes. Financial parameters associated with better managerial performance are found to be positively significant in explaining the probability of belonging to the more efficient latent class. The analysis of latent class membership was consistent with the conjecture that unobservable technological heterogeneity reflected in the existence of the latent classes is related to managerial performance. The findings may support the cause for raising efficiency of Japanese local public hospitals by enhancing the quality of management. Copyright © 2011 John Wiley & Sons, Ltd.

Latent class instrumental variables: A clinical and biostatistical perspective

PubMed Central

Baker, Stuart G.; Kramer, Barnett S.; Lindeman, Karen S.

2015-01-01

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. PMID:26239275

The detection of drugs of abuse in fingerprints using Raman spectroscopy I: latent fingerprints

NASA Astrophysics Data System (ADS)

Day, Joanna S.; Edwards, Howell G. M.; Dobrowski, Steven A.; Voice, Alison M.

2004-02-01

This paper describes the application of Raman spectroscopy to the detection of exogenous substances in latent fingerprints. The scenario considered was that of an individual handling a substance and subsequently depositing a contaminated fingerprint. Five drugs of abuse (codeine phosphate, cocaine hydrochloride, amphetamine sulphate, barbital and nitrazepam) and five non-controlled substances of similar appearance, which may be used in the adulteration of drugs of abuse (caffeine, aspirin, paracetamol, starch and talc), were studied in both sweat-rich and sebum-rich latent fingerprints. The substances studied could be clearly distinguished using their Raman spectra and were all successfully detected in latent fingerprints. Photobleaching was necessary to reduce the fluorescence background in the spectra of some substances. Raman spectra obtained from the substances in sweat-rich latent fingerprints were of a similar quality to spectra that obtained from the substances under normal sampling conditions. Interfering Raman bands arising from latent fingerprint material were present in the spectra obtained from the substances in sebum-rich fingerprints. These bands did not prevent identification of the substances and could be successfully removed by spectral subtraction. The most difficult aspect of the detection of these substances in latent fingerprints was visually locating the substance in the fingerprint in order to obtain a Raman spectrum.

Glycyrrhizic acid alters Kaposi sarcoma–associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes

PubMed Central

Curreli, Francesca; Friedman-Kien, Alvin E.; Flore, Ornella

2005-01-01

Kaposi sarcoma–associated herpesvirus (KSHV) is linked with all clinical forms of Kaposi sarcoma and several lymphoproliferative disorders. Like other herpesviruses, KSHV becomes latent in the infected cells, expressing only a few genes that are essential for the establishment and maintenance of its latency and for the survival of the infected cells. Inhibiting the expression of these latent genes should lead to eradication of herpesvirus infection. All currently available drugs are ineffective against latent infection. Here we show, for the first time to our knowledge, that latent infection with KSHV in B lymphocytes can be terminated by glycyrrhizic acid (GA), a triterpenoid compound earlier shown to inhibit the lytic replication of other herpesviruses. We demonstrate that GA disrupts latent KSHV infection by downregulating the expression of latency-associated nuclear antigen (LANA) and upregulating the expression of viral cyclin and selectively induces cell death of KSHV-infected cells. We show that reduced levels of LANA lead to p53 reactivation, an increase in ROS, and mitochondrial dysfunction, which result in G1 cell cycle arrest, DNA fragmentation, and oxidative stress–mediated apoptosis. Latent genes are involved in KSHV-induced oncogenesis, and strategies to interfere with their expression might prove useful for eradicating latent KSHV infection and have future therapeutic implications. PMID:15765147

Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes.

PubMed

Curreli, Francesca; Friedman-Kien, Alvin E; Flore, Ornella

2005-03-01

Kaposi sarcoma-associated herpesvirus (KSHV) is linked with all clinical forms of Kaposi sarcoma and several lymphoproliferative disorders. Like other herpesviruses, KSHV becomes latent in the infected cells, expressing only a few genes that are essential for the establishment and maintenance of its latency and for the survival of the infected cells. Inhibiting the expression of these latent genes should lead to eradication of herpesvirus infection. All currently available drugs are ineffective against latent infection. Here we show, for the first time to our knowledge, that latent infection with KSHV in B lymphocytes can be terminated by glycyrrhizic acid (GA), a triterpenoid compound earlier shown to inhibit the lytic replication of other herpesviruses. We demonstrate that GA disrupts latent KSHV infection by downregulating the expression of latency-associated nuclear antigen (LANA) and upregulating the expression of viral cyclin and selectively induces cell death of KSHV-infected cells. We show that reduced levels of LANA lead to p53 reactivation, an increase in ROS, and mitochondrial dysfunction, which result in G1 cell cycle arrest, DNA fragmentation, and oxidative stress-mediated apoptosis. Latent genes are involved in KSHV-induced oncogenesis, and strategies to interfere with their expression might prove useful for eradicating latent KSHV infection and have future therapeutic implications.

Geologic reconnaissance and geochemical sampling survey of molybdenum mineralization near Schiestler Peak, Temple Peak Quadrangle, Sublette County, Wyoming

USGS Publications Warehouse

Lee, G.K.; Antweiler, J.C.; Love, J.D.; Benedict, J.F.

1982-01-01

A brief geologic reconnaissance and geochemical survey of molybdenum mineralization near Schiestler Peak, Sublette County, Wyo., indicates that molybdenite occurs in this area as disseminations and blebs in granitic or quartz monzonitic rocks intruded by felsic dikes of similar composition. Samples of stream sediments, panned concentrates from stream sediments, soils, rocks, and water were collected in the geochemical survey. Analytical results show that in reconnaissance, panned concentrates are the best of the sample types used in this study to detect molybdenum mineralization. More detailed analysis of the distribution of the molybdenum is best achieved through the collection of rock samples. Hydrothermal alteration is generally not conspicuous in the study area; however, rock samples that contain molybdenite are usually slightly enriched in silver, copper, lead, and in several instances, gold. Conversely, there appear to be negative associations between molybdenum and zinc and between molybdenum and several of the rare-earth elements. Mo concentrations in the rock samples with no visible molybdenite range from undetectable at a sensitivity of 5 parts per million (ppm) to 700 ppm. Mo content in rock samples containing visible molybdenite ranges from 10 ppm to greater than 2,000 ppm. Stream-sediment values range from undetected to 15 ppm; panned concentrates from undetected to 15 ppm; soils from undetected to 20 ppm. Analyses of the water samples indicate Mo concentrations from 0.8 parts per billion (ppb) to 4.8 ppb. As currently understood, this deposit is not extensive or continuous, but drilling to provide information on the vertical extent of mineralization may alter this opinion.

Evaluation of predictors for the diagnosis of hyperthyroidism in cats.

PubMed

Wakeling, Jennifer; Elliott, Jonathan; Syme, Harriet

2011-01-01

In humans, subclinical hyperthyroidism is diagnosed when serum thyroid hormone concentrations are within the reference range but thyroid stimulating hormone (TSH) concentration is subnormal. In a previous study, a higher prevalence of thyroid nodular disease was found in euthyroid geriatric cats with undetectable TSH (<0.03 ng/mL) compared to those with detectable TSH concentrations, suggesting subclinical hyperthyroidism might also exist in cats. Euthyroid cats with undetectable TSH concentrations have subclinical hyperthyroidism and may subsequently develop overt signs of hyperthyroidism. One-hundred four client-owned cats. In this prospective cohort study, euthyroid geriatric (≥ 9 years) cats were recruited during routine health checks. Plasma biochemistry was performed at baseline and every 6 months thereafter. Total thyroxine and TSH concentrations were determined annually. Short-term follow-up data (within 14 months of recruitment) were used to detect variables at entry that were predictive of the diagnosis of hyperthyroidism, using univariable analysis followed by multivariable logistic regression analysis. Log rank analysis was used to test the association of initial TSH concentration with diagnosis of hyperthyroidism during the total available follow-up. Median (range) follow-up was 26 (0-54) months and annual incidence of hyperthyroidism during the study was 7.4%. Cats that became hyperthyroid within 14 months had higher ALKP activity (P = 0.02) and higher prevalence of goiter (P = .03) at baseline than controls. Cats with undetectable TSH at baseline (29/104; 28%) were significantly (P < .001) more likely to be diagnosed with hyperthyroidism. However, not all cats with undetectable TSH became hyperthyroid during the study. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Evaluating the diagnostic gap: statewide incidence of undiagnosed critical congenital heart disease before newborn screening with pulse oximetry.

PubMed

Mouledoux, Jessica H; Walsh, William F

2013-10-01

Screening for critical congenital heart disease (CCHD) using pulse oximetry has been endorsed by the American Academy of Pediatrics and the American Heart Association. We sought to determine the incidence of undetected CCHD in Tennessee and the diagnostic gap of CCHD in Middle Tennessee prior to screening implementation. The Tennessee Initiative for Perinatal Quality Care (TIPQC) Undetected CCHD Registry is a quality improvement initiative established to identify neonates discharged from the nursery with undetected CCHD. The TIPQC database was queried and a simultaneous review of all neonates with CCHD in the Middle Tennessee region was performed to define the incidence and identify the pre-screen diagnostic gap of undetected CCHD at the time of hospital discharge. In 2011, of 79,462 live births in Tennessee, 12 newborns had undiagnosed CCHD (incidence 15 per 100,000; 95 % CI 9-26 per 100,000). Nine of 12 (75 %) had coarctation of the aorta (CoA). There were no deaths due to undiagnosed CCHD. In the Middle Tennessee region, 6 of 45 neonates with CCHD were missed, for a diagnostic gap of 13 % (95 % CI 6-26 %). Prior to implementation of CCHD screening using pulse oximetry, 12 Tennessee neonates with CCHD were missed by prenatal ultrasound and newborn examination. CoA was the most common lesion missed and is also the CCHD most likely to be missed despite addition of screening using pulse oximetry. Continued evaluation of the diagnostic gap with particular attention to missed diagnoses of CoA should accompany institution of CCHD screening programs.

Heuristics in primary care for recognition of unreported vision loss in older people: a technology development study.

PubMed

Wijeyekoon, Skanda; Kharicha, Kalpa; Iliffe, Steve

2015-09-01

To evaluate heuristics (rules of thumb) for recognition of undetected vision loss in older patients in primary care. Vision loss is associated with ageing, and its prevalence is increasing. Visual impairment has a broad impact on health, functioning and well-being. Unrecognised vision loss remains common, and screening interventions have yet to reduce its prevalence. An alternative approach is to enhance practitioners' skills in recognising undetected vision loss, by having a more detailed picture of those who are likely not to act on vision changes, report symptoms or have eye tests. This paper describes a qualitative technology development study to evaluate heuristics for recognition of undetected vision loss in older patients in primary care. Using a previous modelling study, two heuristics in the form of mnemonics were developed to aid pattern recognition and allow general practitioners to identify potential cases of unreported vision loss. These heuristics were then analysed with experts. Findings It was concluded that their implementation in modern general practice was unsuitable and an alternative solution should be sort.

Positive Reinforcement Training for Blood Collection in Grizzly Bears (Ursus arctos horribilis) Results in Undetectable Elevations in Serum Cortisol Levels: A Preliminary Investigation.

PubMed

Joyce-Zuniga, Nicole M; Newberry, Ruth C; Robbins, Charles T; Ware, Jasmine V; Jansen, Heiko T; Nelson, O Lynne

2016-01-01

Training nonhuman animals in captivity for participation in routine husbandry procedures is believed to produce a lower stress environment compared with undergoing a general anesthetic event for the same procedure. This hypothesis rests largely on anecdotal evidence that the captive subjects appear more relaxed with the trained event. Blood markers of physiological stress responses were evaluated in 4 captive grizzly bears (Ursus arctos horribilis) who were clicker-trained for blood collection versus 4 bears who were chemically immobilized for blood collection. Serum cortisol and immunoglobulin A (IgA) and plasma β-endorphin were measured as indicators of responses to stress. Plasma β-endorphin was not different between the groups. Serum IgA was undetectable in all bears. Serum cortisol was undetectable in all trained bears, whereas chemically immobilized bears had marked cortisol elevations (p < .05). The highest cortisol elevations were found in 2 bears with extensive recent immobilization experience. These findings support the use of positive reinforcement training for routine health procedures to minimize anxiety.

Using High-Dimensional Image Models to Perform Highly Undetectable Steganography

NASA Astrophysics Data System (ADS)

Pevný, Tomáš; Filler, Tomáš; Bas, Patrick

This paper presents a complete methodology for designing practical and highly-undetectable stegosystems for real digital media. The main design principle is to minimize a suitably-defined distortion by means of efficient coding algorithm. The distortion is defined as a weighted difference of extended state-of-the-art feature vectors already used in steganalysis. This allows us to "preserve" the model used by steganalyst and thus be undetectable even for large payloads. This framework can be efficiently implemented even when the dimensionality of the feature set used by the embedder is larger than 107. The high dimensional model is necessary to avoid known security weaknesses. Although high-dimensional models might be problem in steganalysis, we explain, why they are acceptable in steganography. As an example, we introduce HUGO, a new embedding algorithm for spatial-domain digital images and we contrast its performance with LSB matching. On the BOWS2 image database and in contrast with LSB matching, HUGO allows the embedder to hide 7× longer message with the same level of security level.

The Significance of HIV ‘Blips’ in Resource-Limited Settings: Is It the Same? Analysis of the Treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD)

PubMed Central

Kanapathipillai, Rupa; McManus, Hamish; Kamarulzaman, Adeeba; Lim, Poh Lian; Templeton, David J.; Law, Matthew; Woolley, Ian

2014-01-01

Introduction Magnitude and frequency of HIV viral load blips in resource-limited settings, has not previously been assessed. This study was undertaken in a cohort from a high income country (Australia) known as AHOD (Australian HIV Observational Database) and another cohort from a mixture of Asian countries of varying national income per capita, TAHOD (TREAT Asia HIV Observational Database). Methods Blips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed. Results 5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50–≤1000, p = 0.309 for blip 50–≤400 and p = 0.300 for blip 50–≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip. Conclusion Despite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips. PMID:24516527

Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

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

Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.

HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation processmore » including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Furthermore, our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.« less

Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

DOE PAGES

Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; ...

2015-12-22

HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation processmore » including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Furthermore, our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.« less

Risk factors for failure to complete a course of latent tuberculosis infection treatment in Salvador, Brazil.

PubMed

Machado, Almério; Finkmoore, B; Emodi, K; Takenami, I; Barbosa, T; Tavares, M; Reis, M G; Arruda, S; Riley, L W

2009-06-01

Although treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) control in countries such as the United States, it is not widely practiced in most TB-endemic countries. To examine the practice of and adherence to LTBI treatment in a high-risk population in Brazil. We followed household contacts (HHCs) of patients hospitalized with pulmonary TB in Salvador, Brazil, for 6 months after they initiated LTBI treatment with isoniazid (INH). HHCs were asked to return to the hospital once a month for 6 months for follow-up visits and INH refills. Of 101 HHCs who initiated LTBI treatment, 54 (53.5%) completed the 6-month regimen. The risk of treatment non-completion was significantly higher in HHCs who reported side effects to INH (RR 2.69, 95%CI 1.3-5.8, P = 0.01), and in those who had to take two buses for a one-way trip to the hospital (RR 1.8, 95%CI 1.01-3.3, P = 0.04). Of the 101 HHCs, 29 (28.7%) did not return for any follow-up visits; these HHCs were significantly more likely to have a 2-bus commute to the hospital compared to HHCs who completed treatment (OR 20.69, 95%CI 2.1-208.4, P = 0.01). Nearly 50% of HHCs at high risk for developing TB completed a 6-month course of LTBI treatment. Completion of LTBI treatment was most affected by medication intolerance and commuting difficulties for follow-up visits.

Timing of hospital admission in labour: latent versus active phase, mode of birth and intrapartum interventions. A correlational study.

PubMed

Rota, A; Antolini, L; Colciago, E; Nespoli, A; Borrelli, S E; Fumagalli, S

2017-10-17

Hospitalization of women in latent labour often leads to a cascade of unnecessary intrapartum interventions, to avoid potential disadvantages the recommendation should be to stay at home to improve women's experience and perinatal outcomes. The primary aim of this study was to investigate the association between hospital admission diagnosis (latent vs active phase) and mode of birth. The secondary aim was to explore the relationship between hospital admission diagnosis, intrapartum intervention rates and maternal/neonatal outcomes. A correlational study was conducted in a large Italian maternity hospital. Data from January 2013 to December 2014 were collected from the hospital electronic records. 1.446 records of low risk women were selected. These were dichotomized into two groups based on admission diagnosis: 'latent phase' or 'active phase' of labour. 52.7% of women were admitted in active labour and 47.3% in the latent phase. Women in the latent phase group were more likely to experience a caesarean section or an instrumental birth, artificial rupture of membranes, oxytocin augmentation and epidural analgesia. Admission in the latent phase was associated with higher intrapartum interventions, which were statistically correlated to the mode of birth. Women admitted in the latent phase were more likely to experience intrapartum interventions, which increase the probability of caesarean section. Maternity services should be organized around women and families needs, providing early labour support, to enable women to feel reassured facilitating their admission in labour to avoid the cascade of intrapartum interventions which increases the risk of caesarean section. Copyright © 2017 Australian College of Midwives. All rights reserved.

Early Changes by 18Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques

PubMed Central

Coleman, M. Teresa; Maiello, Pauline; Tomko, Jaime; Frye, Lonnie James; Fillmore, Daniel; Janssen, Christopher; Klein, Edwin

2014-01-01

Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. 18Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (n = 10) were infected with low-dose M. tuberculosis with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (n = 3) or latent infection (n = 6), with one “percolator” monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies. PMID:24664509

Detection of anti-HspX antibodies and HspX protein in patient sera for the identification of recent latent infection by Mycobacterium tuberculosis

PubMed Central

García-Jacobo, Paola; Rivera-Morales, Lydia G.; Barber, James; Karls, Russell; Haas, Debra; Helms, Shelly; Gupta, Tuhina; Blumberg, Henry; Tapia, Jane; Luna-Cruz, Itza; Rendon, Adrián; Vargas-Villarreal, Javier; Vera-Cabrera, Lucio; Rodríguez-Padilla, Cristina

2017-01-01

Mycobacterium tuberculosis is a pathogen causing tuberculosis (TB) a spectrum of disease including acute and asymptomatic latent stages. Identifying and treating latently-infected patients constitutes one of the most important impediments to TB control efforts. Those individuals can remain undiagnosed for decades serving as potential reservoirs for disease reactivation. Tests for the accurate diagnosis of latent infection currently are unavailable. HspX protein (α-crystallin), encoded by Rv2031c gene, is produced in vitro by M. tuberculosis during stationary growth phase and hypoxic or acidic culture conditions. In this study, using standard, and Luminex xMAP® bead capture ELISA, respectively, we report on detection of anti-HspX IgG and IgM antibodies and HspX protein in sera from acute and latent TB patients. For the antibody screen, levels of IgG and IgM antibodies were similar between non-infected and active TB patients; however, individuals classified into the group with latent TB showed higher values of anti-HspX IgM (p = 0.003) compared to active TB patients. Using the bead capture antigen detection assay, HspX protein was detected in sera from 56.5% of putative latent cases (p< 0.050) compared to the background median with an average of 9,900 pg/ml and a range of 1,000 to 36,000 pg/ml. Thus, presence of anti-HspX IgM antibodies and HspX protein in sera may be markers of latent TB. PMID:28813434

Paths to tobacco abstinence: A repeated-measures latent class analysis.

PubMed

McCarthy, Danielle E; Ebssa, Lemma; Witkiewitz, Katie; Shiffman, Saul

2015-08-01

Knowledge of smoking change processes may be enhanced by identifying pathways to stable abstinence. We sought to identify latent classes of smokers based on their day-to-day smoking status in the first weeks of a cessation attempt. We examined treatment effects on class membership and compared classes on baseline individual differences and 6-month abstinence rates. In this secondary analysis of a double-blind randomized placebo-controlled clinical trial (N = 1,433) of 5 smoking cessation pharmacotherapies (nicotine patch, nicotine lozenge, bupropion SR, patch and lozenge, or bupropion SR and lozenge), we conducted repeated-measures latent class analysis of daily smoking status (any smoking vs. none) for the first 27 days of a quit attempt. Treatment and covariate relations with latent class membership were examined. Distal outcome analysis compared confirmed 6-month abstinence rates among the latent classes. A 5-class solution was selected. Three-quarters of smokers were in stable smoking or abstinent classes, but 25% were in classes with unstable abstinence probabilities over time. Active treatment (compared to placebo), and particularly the patch and lozenge combination, promoted early quitting. Latent classes differed in 6-month abstinence rates and on several baseline variables, including nicotine dependence, quitting history, self-efficacy, sleep disturbance, and minority status. Repeated-measures latent class analysis identified latent classes of smoking change patterns affected by treatment, related to known risk factors, and predictive of distal outcomes. Tracking behavior early in a change attempt may identify prognostic patterns of change and facilitate adaptive treatment planning. (c) 2015 APA, all rights reserved).

A further assessment of the Hall-Rodriguez theory of latent inhibition.

PubMed

Leung, Hiu Tin; Killcross, A S; Westbrook, R Frederick

2013-04-01

The Hall-Rodriguez (G. Hall & G. Rodriguez, 2010, Associative and nonassociative processes in latent inhibition: An elaboration of the Pearce-Hall model, in R. E. Lubow & I. Weiner, Eds., Latent inhibition: Data, theories, and applications to schizophrenia, pp. 114-136, Cambridge, England: Cambridge University Press) theory of latent inhibition predicts that it will be deepened when a preexposed target stimulus is given additional preexposures in compound with (a) a novel stimulus or (b) another preexposed stimulus, and (c) that deepening will be greater when the compound contains a novel rather than another preexposed stimulus. A series of experiments studied these predictions using a fear conditioning procedure with rats. In each experiment, rats were preexposed to 3 stimuli, 1 (A) taken from 1 modality (visual or auditory) and the remaining 2 (X and Y) taken from another modality (auditory or visual). Then A was compounded with X, and Y was compounded with a novel stimulus (B) taken from the same modality as A. A previous series of experiments (H. T. Leung, A. S. Killcross, & R. F. Westbrook, 2011, Additional exposures to a compound of two preexposed stimuli deepen latent inhibition, Journal of Experimental Psychology: Animal Behavior Processes, Vol. 37, pp. 394-406) compared A with Y, finding that A was more latently inhibited than Y, the opposite of what was predicted. The present experiments confirmed that A was more latently inhibited than Y, showed that this was due to A entering the compound more latently inhibited than Y, and finally, that a comparison of X and Y confirmed the 3 predictions made by the theory.

Modeling Pacing Behavior and Test Speededness Using Latent Growth Curve Models

ERIC Educational Resources Information Center

Kahraman, Nilufer; Cuddy, Monica M.; Clauser, Brian E.

2013-01-01

This research explores the usefulness of latent growth curve modeling in the study of pacing behavior and test speededness. Examinee response times from a high-stakes, computerized examination, collected before and after the examination was subjected to a timing change, were analyzed using a series of latent growth curve models to detect…

Variable-Length Computerized Adaptive Testing Using the Higher Order DINA Model

ERIC Educational Resources Information Center

Hsu, Chia-Ling; Wang, Wen-Chung

2015-01-01

Cognitive diagnosis models provide profile information about a set of latent binary attributes, whereas item response models yield a summary report on a latent continuous trait. To utilize the advantages of both models, higher order cognitive diagnosis models were developed in which information about both latent binary attributes and latent…

Application of Local Linear Embedding to Nonlinear Exploratory Latent Structure Analysis

ERIC Educational Resources Information Center

Wang, Haonan; Iyer, Hari

2007-01-01

In this paper we discuss the use of a recent dimension reduction technique called Locally Linear Embedding, introduced by Roweis and Saul, for performing an exploratory latent structure analysis. The coordinate variables from the locally linear embedding describing the manifold on which the data reside serve as the latent variable scores. We…

Nonlinear Structured Growth Mixture Models in M"plus" and OpenMx

ERIC Educational Resources Information Center

Grimm, Kevin J.; Ram, Nilam; Estabrook, Ryne

2010-01-01

Growth mixture models (GMMs; B. O. Muthen & Muthen, 2000; B. O. Muthen & Shedden, 1999) are a combination of latent curve models (LCMs) and finite mixture models to examine the existence of latent classes that follow distinct developmental patterns. GMMs are often fit with linear, latent basis, multiphase, or polynomial change models…

A Latent Class Approach to Estimating Test-Score Reliability

ERIC Educational Resources Information Center

van der Ark, L. Andries; van der Palm, Daniel W.; Sijtsma, Klaas

2011-01-01

This study presents a general framework for single-administration reliability methods, such as Cronbach's alpha, Guttman's lambda-2, and method MS. This general framework was used to derive a new approach to estimating test-score reliability by means of the unrestricted latent class model. This new approach is the latent class reliability…

Testing Manifest Monotonicity Using Order-Constrained Statistical Inference

ERIC Educational Resources Information Center

Tijmstra, Jesper; Hessen, David J.; van der Heijden, Peter G. M.; Sijtsma, Klaas

2013-01-01

Most dichotomous item response models share the assumption of latent monotonicity, which states that the probability of a positive response to an item is a nondecreasing function of a latent variable intended to be measured. Latent monotonicity cannot be evaluated directly, but it implies manifest monotonicity across a variety of observed scores,…