Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

NASA Astrophysics Data System (ADS)

Lemaire-Vieille, Catherine; Schulze, Tobias; Podevin-Dimster, Valérie; Follet, Jérome; Bailly, Yannick; Blanquet-Grossard, Françoise; Decavel, Jean-Pierre; Heinen, Ernst; Cesbron, Jean-Yves

2000-05-01

The expression of the cellular form of the prion protein (PrPc) gene is required for prion replication and neuroinvasion in transmissible spongiform encephalopathies. The identification of the cell types expressing PrPc is necessary to understanding how the agent replicates and spreads from peripheral sites to the central nervous system. To determine the nature of the cell types expressing PrPc, a green fluorescent protein reporter gene was expressed in transgenic mice under the control of 6.9 kb of the bovine PrP gene regulatory sequences. It was shown that the bovine PrP gene is expressed as two populations of mRNA differing by alternative splicing of one 115-bp 5' untranslated exon in 17 different bovine tissues. The analysis of transgenic mice showed reporter gene expression in some cells that have been identified as expressing PrP, such as cerebellar Purkinje cells, lymphocytes, and keratinocytes. In addition, expression of green fluorescent protein was observed in the plexus of the enteric nervous system and in a restricted subset of cells not yet clearly identified as expressing PrP: the epithelial cells of the thymic medullary and the endothelial cells of both the mucosal capillaries of the intestine and the renal capillaries. These data provide valuable information on the distribution of PrPc at the cellular level and argue for roles of the epithelial and endothelial cells in the spread of infection from the periphery to the brain. Moreover, the transgenic mice described in this paper provide a model that will allow for the study of the transcriptional activity of the PrP gene promoter in response to scrapie infection.

Development of a geographic visualization and communications systems (GVCS) for monitoring remote vehicles

DOT National Transportation Integrated Search

1998-03-30

The purpose of this project is to integrate a variety of geographic information systems : capabilities and telecommunication technologies for potential use in geographic network and : visualization applications. The specific technical goals of the pr...

Lessons learned from the experiences of informal PrEP users in France: results from the ANRS-PrEPage study.

PubMed

Rivierez, I; Quatremere, G; Spire, B; Ghosn, J; Rojas Castro, D

2018-05-30

Before January 2016, Pre-Exposure Prophylaxis (PrEP), a new biomedical HIV-prevention tool, was only available in France via ANRS-Ipergay clinical study but informal use was reported outside this setting. PrEPage qualitative study reports profiles and experiences of participants who used PrEP outside of a biomedical trial before this prevention method was authorized. Between March 2015 and February 2016, a cross-section of twenty-four informal PrEP users, mostly MSM, was recruited to complete in-depth semi-structured interviews. While ANRS-Ipergay was still ongoing (2012-2016), participants described their initiation to PrEP, the way they used it and the difficulties they faced to acquire antiretroviral drugs in an environment where PrEP was still not widely known and often criticized . Through the testimonies, different user profiles and motivation toward informal PrEP use emerged: (a) participants who have increasing difficulties using condoms, (b) "opportunists" who tried PrEP without the intention of using it regularly and (c) participants with a risk aversion who sought additional protection against HIV. Participants chose to use PrEP and/or their usual prevention strategies depending on available supplies, type of partners and individual attitudes toward risk. The feeling of living a safer sex life helped participants to outweigh the fear of possible toxicity and drug resistance. Participants' needs and expectations about PrEP implementation in France were also presented.

Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification

PubMed Central

Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

2016-01-01

Prions are formed of misfolded assemblies (PrPSc) of the variably N-glycosylated cellular prion protein (PrPC). In infected species, prions replicate by seeding the conversion and polymerization of host PrPC. Distinct prion strains can be recognized, exhibiting defined PrPSc biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrPSc assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrPC glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrPC species of interest as substrate. Applying the technique to PrPC glycosylation mutants expressing cells revealed that neither PrPC nor PrPSc glycoform stoichiometry was instrumental to PrPSc formation and strainness perpetuation. Our study supports the view that strain properties, including PrPSc glycotype are enciphered within PrPSc structural backbone, not in the attached glycans. PMID:27384922

Knowledge of and interest in using preexposure prophylaxis for HIV prevention among men who have sex with men in Thailand.

PubMed

Sineath, R Craig; Finneran, Catherine; Sullivan, Patrick; Sanchez, Travis; Smith, Dawn K; Griensven, Frits van; Wimonsate, Wipas; Stephenson, Rob

2013-01-01

Little is known about HIV preexposure prophylaxis (PrEP) acceptability among men who have sex with men (MSM) in Thailand. The authors recruited an online convenience sample of Thai MSM (n = 404) to assess the knowledge of and interest in PrEP. Less than 7% had heard of PrEP; however, 35% indicated interest in PrEP after an explanation of its possible efficacy. Regression modeling demonstrated that HIV knowledge and risk behavior, but not demographics, are significant predictors of PrEP interest. More information and education about PrEP is necessary and more research is needed to examine PrEP acceptability and to inform the message for PrEP uptake.

PrEP awareness and decision-making for Latino MSM in San Antonio, Texas

PubMed Central

García, Moctezuma; Harris, Allyssa L.

2017-01-01

Pre-Exposure Prophylaxis (PrEP) has been promoted among high-risk populations as an effective HIV biomedical intervention. However, limited research is available on the significance of culturally informed biomedical interventions for Latino MSM. A total of 159 self-administered Internet surveys were completed by Latino MSM ages 21–30 in San Antonio, Texas. The purpose of this research was to develop an instrument that measured Latino MSM attitudes and beliefs towards PrEP, identify associations between demographic factors and PrEP related factors and to suggest culturally appropriate strategies for the promotion of PrEP among the Latino MSM population. Research findings revealed implications for PrEP at the structural and individual level for Latino MSM. Structural level indicators emphasized the importance for raising PrEP awareness among Latino MSM in regards to PrEP related expenses, ameliorating stigmatization of high-risk populations, enhancing access to PrEP informed medical providers, and address mistrust of the government and medical providers role on addressing health disparities among Latino MSM. Overall, the findings for individual factors emphasize the need for patient-centered interventions for Latino MSM. Latino MSM currently on PrEP require supplemental resources to enhance PrEP adherence. Latino MSM not on PrEP require alternate options for PrEP delivery and/or cognitive behavioral approaches minimizing HIV risk behavior for Latino MSM concerned with PrEP toxicity, which may require non-biomedical interventions. Integration of Latino MSM currently on PrEP as peer educators provides a valuable resource for developing culturally informed PrEP interventions for Latino MSM. Peer educators are able to share their experiential knowledge of PrEP contextualized through cultural norms, beliefs, and values. PMID:28953905

Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.

PubMed

Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

2016-07-07

Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N-glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans.

Soil zinc content, groundwater usage, and prostate cancer incidence in South Carolina.

PubMed

Wagner, Sara E; Burch, James B; Hussey, Jim; Temples, Tom; Bolick-Aldrich, Susan; Mosley-Broughton, Catishia; Liu, Yuan; Hebert, James R

2009-04-01

Prostate cancer (PrCA) incidence in South Carolina (SC) exceeds the national average, particularly among African Americans (AAs). Though data are limited, low environmental zinc exposures and down-regulation of prostatic zinc transporter proteins among AAs may explain, in part, the racial PrCA disparity. Age-adjusted PrCA rates were calculated by census tract. Demographic data were obtained from the 1990 census. Hazardous waste site locations and soil zinc concentrations were obtained from existing federal and state databases. A geographic information system and Poisson regression were used to test the hypothesis that census tracts with reduced soil zinc concentrations, elevated groundwater use, or more agricultural or hazardous waste sites had elevated PrCA risks. Census tracts with high groundwater use and low zinc concentrations had higher PrCA rate ratios (RR: 1.270; 95% confidence interval: 1.079, 1.505). This effect was not more apparent in areas populated primarily by AAs. Increased PrCA rates were associated with reduced soil zinc concentrations and elevated groundwater use, although this observation is not likely to contribute to SC's racial PrCA disparity. Statewide mapping and statistical modeling of relationships between environmental factors, demographics, and cancer incidence can be used to screen hypotheses focusing on novel PrCA risk factors.

Olfactory behavior and physiology are disrupted in prion protein knockout mice.

PubMed

Le Pichon, Claire E; Valley, Matthew T; Polymenidou, Magdalini; Chesler, Alexander T; Sagdullaev, Botir T; Aguzzi, Adriano; Firestein, Stuart

2009-01-01

The prion protein PrP(C) is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrP(C) rather than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp(-/-) mice were rescued by transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system.

Prion protein β2–α2 loop conformational landscape

PubMed Central

Caldarulo, Enrico; Wüthrich, Kurt; Parrinello, Michele

2017-01-01

In transmissible spongiform encephalopathies (TSEs), which are lethal neurodegenerative diseases that affect humans and a wide range of other mammalian species, the normal “cellular” prion protein (PrPC) is transformed into amyloid aggregates representing the “scrapie form” of the protein (PrPSc). Continued research on this system is of keen interest, since new information on the physiological function of PrPC in healthy organisms is emerging, as well as new data on the mechanism of the transformation of PrPC to PrPSc. In this paper we used two different approaches: a combination of the well-tempered ensemble (WTE) and parallel tempering (PT) schemes and metadynamics (MetaD) to characterize the conformational free-energy surface of PrPC. The focus of the data analysis was on an 11-residue polypeptide segment in mouse PrPC(121–231) that includes the β2–α2 loop of residues 167–170, for which a correlation between structure and susceptibility to prion disease has previously been described. This study includes wild-type mouse PrPC and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an integrative manner the available experimental data on PrPC, providing quantitative insights into the nature of the structural transition-related function of the β2–α2 loop. PMID:28827331

Attitudes, Beliefs, and Barriers to PrEP Among Trans Men.

PubMed

Rowniak, Stefan; Ong-Flaherty, Chenit; Selix, Nancy; Kowell, Niko

2017-08-01

The study examined the attitudes and knowledge of transgender men (trans men) regarding pre-exposure prophylaxis (PrEP) for HIV. Three focus groups of trans men were conducted with a trans male facilitator for a total of 21 participants. Six themes were identified; the range of information about PrEP and possible side effects, the economic realities for trans men, finding a trans-competent provider, trans male sexuality, the importance of contraception, and condom use. Despite identified risk and some information that has been disseminated, many trans men still lack adequate information regarding PrEP. There exist significant barriers to PrEP access for trans men. Participants commented that many providers avoid important discussions regarding sexuality and contraception. The education of health care professionals must include competency in working with transgender populations. More research is needed with regard to interactions between PrEP, testosterone, and hormonal contraception.

Public Relations Programs. The Best of ERIC, Number 36.

ERIC Educational Resources Information Center

ERIC Clearinghouse on Educational Management, Eugene, OR.

This bibliography contains annotations of 11 documents and journal articles covering various aspects of school public relations, including how to start a PR program, how to improve information dissemination and information gathering, the PR aspects of school violence, the role of the school business manager in PR, school publications, the PR…

ANCA / MPO / PR3 Antibodies Test

MedlinePlus

... normal limits." For more information, please read the article Reference Ranges and What They Mean . What is being tested? Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies produced by a person's immune system that mistakenly target and attack proteins within the ...

Optimizing content for pre-exposure prophylaxis (PrEP) counseling for men who have sex with men: Perspectives of PrEP users and high-risk PrEP naïve men.

PubMed

Wade Taylor, S; Mayer, Kenneth H; Elsesser, Steven M; Mimiaga, Matthew J; O'Cleirigh, Conall; Safren, Steven A

2014-05-01

Existing trials of antiretroviral (ARV) medication as chemoprophylaxis against HIV reveal that the degree of protection is primarily dependent on product adherence. However, there is a lack of data on targets for behavioral interventions to improve adherence to ARV as prevention. Information from individuals who have used ARV as pre-exposure prophylaxis (PrEP) can inform behavioral intervention development. Thirty-nine HIV-uninfected MSM at high risk for HIV acquisition participated in one of four semi-structured focus groups. Two of the focus groups consisted of MSM who had been prescribed and used PrEP in the context of a clinical trial; the other two consisted of high-risk MSM who had not previously used PrEP. An in-depth, within-case/across-case content analysis resulted in six descriptive themes potentially salient for a PrEP adherence behavioral intervention: (1) motivations to use PrEP, (2) barriers to PrEP use, (3) facilitators to PrEP use, (4) sexual decision-making in the context of PrEP, (5) prospective PrEP education content, and, (6) perceived effective characteristics of PrEP delivery personnel. Addressing these themes in behavioral interventions in the context of prescribing PrEP may result in the optimal "packaging" public health programs that implement PrEP for high-risk MSM.

Active imaging with the aids of polarization retrieve in turbid media system

NASA Astrophysics Data System (ADS)

Tao, Qiangqiang; Sun, Yongxuan; Shen, Fei; Xu, Qiang; Gao, Jun; Guo, Zhongyi

2016-01-01

We propose a novel active imaging based on the polarization retrieve (PR) method in turbid media system. In our simulations, the Monte Carlo (MC) algorithm has been used to investigate the scattering process between the incident photons and the scattering particles, and the visually concordant object but with different polarization characteristics in different regions, has been selected as the original target that is placed in the turbid media. Under linearly and circularly polarized illuminations, the simulation results demonstrate that the corresponding polarization properties can provide additional information for the imaging, and the contrast of the polarization image can also be enhanced greatly compared to the simplex intensity image in the turbid media. Besides, the polarization image adjusted by the PR method can further enhance the visibility and contrast. In addition, by PR imaging method, with the increasing particles' size in Mie's scale, the visibility can be enhanced, because of the increased forward scattering effect. In general, in the same circumstance, the circular polarization images can offer a better contrast and visibility than that of linear ones. The results indicate that the PR imaging method is more applicable to the scattering media system with relatively larger particles such as aerosols, heavy fog, cumulus, and seawater, as well as to biological tissues and blood media.

Pattern recognition and image processing for environmental monitoring

NASA Astrophysics Data System (ADS)

Siddiqui, Khalid J.; Eastwood, DeLyle

1999-12-01

Pattern recognition (PR) and signal/image processing methods are among the most powerful tools currently available for noninvasively examining spectroscopic and other chemical data for environmental monitoring. Using spectral data, these systems have found a variety of applications employing analytical techniques for chemometrics such as gas chromatography, fluorescence spectroscopy, etc. An advantage of PR approaches is that they make no a prior assumption regarding the structure of the patterns. However, a majority of these systems rely on human judgment for parameter selection and classification. A PR problem is considered as a composite of four subproblems: pattern acquisition, feature extraction, feature selection, and pattern classification. One of the basic issues in PR approaches is to determine and measure the features useful for successful classification. Selection of features that contain the most discriminatory information is important because the cost of pattern classification is directly related to the number of features used in the decision rules. The state of the spectral techniques as applied to environmental monitoring is reviewed. A spectral pattern classification system combining the above components and automatic decision-theoretic approaches for classification is developed. It is shown how such a system can be used for analysis of large data sets, warehousing, and interpretation. In a preliminary test, the classifier was used to classify synchronous UV-vis fluorescence spectra of relatively similar petroleum oils with reasonable success.

Evaluation of critical distances for energy transfer between Pr3+ and Ce3+ in yttrium aluminium garnet

NASA Astrophysics Data System (ADS)

Zeng, Peng; Wei, Xiantao; Zhou, Shaoshuai; Yin, Min; Chen, Yonghu

2016-09-01

A series of Pr3+/Ce3+ doped yttrium aluminium garnet (Y3Al5O12 or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr3+ and Ce3+ for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr3+/Ce3+ were measured and analyzed, and it revealed that the reabsorption between Pr3+ and Ce3+ was so weak that it can be ignored, and the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr3+ state with a Ce3+ ion, the optimal distance of Ce3+ from Pr3+ was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y3+ sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr3+/Ce3+ doped YAG and other similar systems.

Practical and Theoretical Requirements for Controlling Rater Stringency in Peer Review.

ERIC Educational Resources Information Center

Cason, Gerald J.; Cason, Carolyn L.

This study describes a computer based, performance rating information processing system, performance rating theory, and programs for the application of the theory to obtain ratings free from the effects of reviewer stringency in reviewing abstracts of conference papers. Originally, the Performance Rating (PR) System was used to evaluate the…

Willingness to Use Pre-Exposure Prophylaxis (PrEP): An Empirical Test of the Information-Motivation-Behavioral Skills (IMB) Model among High-Risk Drug Users in Treatment.

PubMed

Shrestha, Roman; Altice, Frederick L; Huedo-Medina, Tania B; Karki, Pramila; Copenhaver, Michael

2017-05-01

Evidence from recent pre-exposure prophylaxis (PrEP) trials has demonstrated its safety and efficacy in significantly reducing the risk of HIV acquisition for those who are at considerable risk of acquiring HIV infection. With a rapid increase in the amount of research on the efficacy of PrEP for HIV prevention, complementary research on the willingness to use PrEP has grown, especially among MSM, but limited research has been focused among people who use drugs (PWUD). As part of the formative process, we utilized the information-motivation-behavioral skills (IMB) model of health behavior change to characterize and guide intervention development for promoting willingness to use PrEP among high-risk PWUD. The analysis included 400 HIV-negative high-risk PWUD enrolled in a community-based methadone maintenance treatment who reported drug- and/or sex-related HIV risk behaviors in the past 6-months. Analyses revealed support for the IMB model as PrEP-related behavioral skills were found to mediate the influence of PrEP-related information and motivation on willingness to use PrEP. The results provide evidence as to the utility of the IMB model to increase willingness to use PrEP among high-risk PWUD. It therefore makes an important contribution to our understanding of the applicability of theoretically-grounded models of willingness to use PrEP among high-risk PWUD, who are one of the key risk populations who could benefit from the use of PrEP.

Willingness to Use Pre-Exposure Prophylaxis (PrEP): An Empirical Test of the Information-Motivation-Behavioral Skills (IMB) Model among High-Risk Drug Users in Treatment

PubMed Central

Shrestha, Roman; Altice, Frederick L.; Huedo-Medina, Tania B.; Karki, Pramila; Copenhaver, Michael

2016-01-01

Evidence from recent pre-exposure prophylaxis (PrEP) trials has demonstrated its safety and efficacy in significantly reducing the risk of HIV acquisition for those who are at considerable risk of acquiring HIV infection. With a rapid increase in the amount of research on the efficacy of PrEP for HIV prevention, complementary research on the willingness to use PrEP has grown, especially among MSM, but limited research has been focused among people who use drugs (PWUD). As part of the formative process, we utilized the Information-Motivation-Behavioral Skills (IMB) model of health behavior change to characterize and guide intervention development for promoting willingness to use PrEP among high-risk PWUD. The analysis included 400 HIV-negative high-risk PWUD enrolled in a community-based methadone maintenance treatment who reported drug- and/or sex-related HIV risk behaviors in the past 6-months. Analyses revealed support for the IMB model as PrEP-related behavioral skills were found to mediate the influence of PrEP-related information and motivation on willingness to use PrEP. The results provide evidence as to the utility of the IMB model to increase willingness to use PrEP among high-risk PWUD. It therefore makes an important contribution to our understanding of the applicability of theoretically-grounded models of willingness to use PrEP among high-risk PWUD, who are one of the key risk populations who could benefit from the use of PrEP. PMID:27990587

Willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia: findings from a qualitative study

PubMed Central

Bourne, Adam; Cassolato, Matteo; Thuan Wei, Clayton Koh; Wang, Bangyuan; Pang, Joselyn; Lim, Sin How; Azwa, Iskandar; Yee, Ilias; Mburu, Gitau

2017-01-01

Abstract Background: Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake. Methods: As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis. Results: Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to “at-risk” men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours. Conclusions: This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV. PMID:28782336

Willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia: findings from a qualitative study.

PubMed

Bourne, Adam; Cassolato, Matteo; Thuan Wei, Clayton Koh; Wang, Bangyuan; Pang, Joselyn; Lim, Sin How; Azwa, Iskandar; Yee, Ilias; Mburu, Gitau

2017-08-02

Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake. As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis. Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to "at-risk" men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours. This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV.

“Support Your Client at the Space That They're in”: HIV Pre-Exposure Prophylaxis (PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation

PubMed Central

Magnus, Manya; Mayer, Kenneth H.; Krakower, Douglas S.; Eldahan, Adam I.; Hawkins, Lauren A. Gaston; Underhill, Kristen; Hansen, Nathan B.; Kershaw, Trace S.; Betancourt, Joseph R.; Dovidio, John F.

2017-01-01

Abstract Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and evidence that most PrEP users do not engage in risk compensation (i.e., increased risk behavior due to a perceived decrease in HIV susceptibility), some healthcare providers report patient risk compensation to be a deterrent to prescribing PrEP. Overcoming this barrier is essential to supporting PrEP access and uptake among people at risk for HIV. To inform such efforts, this qualitative study explored PrEP-related risk compensation attitudes among providers with firsthand experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were HIV specialists, were recruited through direct outreach and referral from colleagues and other participants. Individual 90-min semistructured interviews were conducted by phone or in person from September 2014 through February 2015, transcribed, and thematically analyzed. Three attitudinal themes emerged: (1) providers' role is to support patients in making informed decisions, (2) risk behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e., PrEP confers net protection, even with added behavioral risk), and (3) PrEP-related risk compensation is unduly stigmatized within and beyond the healthcare community. Participants were critical of other healthcare providers' negative judgment of patients and reluctance to prescribe PrEP due to anticipated risk compensation. Several providers also acknowledged an evolution in their thinking from initial ambivalence toward greater acceptance of PrEP and PrEP-related behavior change. PrEP providers' insights about risk compensation may help to address unsubstantiated concerns about PrEP-related risk compensation and challenge the acceptability of withholding PrEP on these grounds. PMID:28414261

PR-PR: Cross-Platform Laboratory Automation System

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

Linshiz, G; Stawski, N; Goyal, G

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Goldenmore » Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.« less

PR-PR: cross-platform laboratory automation system.

PubMed

Linshiz, Gregory; Stawski, Nina; Goyal, Garima; Bi, Changhao; Poust, Sean; Sharma, Monica; Mutalik, Vivek; Keasling, Jay D; Hillson, Nathan J

2014-08-15

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.

Preexposure Prophylaxis Modality Preferences Among Men Who Have Sex With Men and Use Social Media in the United States.

PubMed

Hall, Eric William; Heneine, Walid; Sanchez, Travis; Sineath, Robert Craig; Sullivan, Patrick

2016-05-19

Preexposure prophylaxis (PrEP) is available as a daily pill for preventing infection with the human immunodeficiency virus (HIV). Innovative methods of administering PrEP systemically or topically are being discussed and developed. The objective of our study was to assess attitudes toward different experimental modalities of PrEP administration. From April to July 2015, we recruited 1106 HIV-negative men who have sex with men through online social media advertisements and surveyed them about their likelihood of using different PrEP modalities. Participants responded to 5-point Likert-scale items indicating how likely they were to use each of the following PrEP modalities: a daily oral pill, on-demand pills, periodic injection, penile gel (either before or after intercourse), rectal gel (before/after), and rectal suppository (before/after). We used Wilcoxon signed rank tests to determine whether the stated likelihood of using any modality differed from daily oral PrEP. Related items were combined to assess differences in likelihood of use based on tissue or time of administration. Participants also ranked their interest in using each modality, and we used the modified Borda count method to determine consensual rankings. Most participants indicated they would be somewhat likely or very likely to use PrEP as an on-demand pill (685/1105, 61.99%), daily oral pill (528/1036, 50.97%), injection (575/1091, 52.70%), or penile gel (438/755, 58.01% before intercourse; 408/751, 54.33% after). The stated likelihoods of using on-demand pills (median score 4) and of using a penile gel before intercourse (median 4) were both higher than that of using a daily oral pill (median 4, P<.001 and P=.001, respectively). Compared with a daily oral pill, participants reported a significantly lower likelihood of using any of the 4 rectal modalities (Wilcoxon signed rank test, all P<.001). On 10-point Likert scales created by combining application methods, the reported likelihood of using a penile gel (median 7) was higher than that of using a rectal gel (median 6, P<.001), which was higher than the likelihood of using a rectal suppository (median 6, P<.001). The modified Borda count ranked on-demand pills as the most preferred modality. There was no difference in likelihood of use of PrEP (gel or suppository) before or after intercourse. Participants typically prefer systemic PrEP and are less likely to use a modality that is administered rectally. Although most of these modalities are seen as favorable or neutral, attitudes may change as information about efficacy and application becomes available. Further data on modality preference across risk groups will better inform PrEP development.

PROMIS Peer Relationships Short Form: How Well Does Self-Report Correlate With Data From Peers?

PubMed

Devine, Katie A; Willard, Victoria W; Hocking, Matthew C; Stapleton, Jerod L; Rotter, David; Bukowski, William M; Noll, Robert B

2018-05-24

To examine the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS®) peer relationships short form (PR-SF), including association with peer-reported friendships, likeability, and social reputation. 203 children (Mage = 10.12 years, SD = 2.37, range = 6-14) in Grades 1-8 completed the 8-item PR-SF and friendship nominations, like ratings, and social reputation measures about their peers during 2 classroom visits approximately 4 months apart, as part of a larger study. A confirmatory factor analysis, followed by an exploratory factor analysis, was conducted to examine the factor structure of the PR-SF. Spearman correlations between the PR-SF and peer-reported outcomes evaluated construct validity. For the PR-SF, a 2-factor solution demonstrated better fit than a 1-factor solution. The 2 factors appear to assess friendship quality (3 items) and peer acceptance (5 items). Reliability was marginal for the friendship quality factor (.66) but adequate for the acceptance factor (.85); stability was .34 for the PR-SF over 4 months. The PR-SF (8 items) and acceptance factor (5 items) both had modest but significant correlations with measures of friendship (rs = .25-.27), likeability (rs = .21-.22), and social reputation (rs = .29-.44). The PR-SF appears to be measuring two distinct aspects of social functioning. The 5-item peer acceptance scale is modestly associated with peer-reported friendship, likeability, and social reputation. Although not a replacement for peer-reported outcomes, the PR-SF is a promising patient-reported outcome for peer relationships in youth.

Perceptions of and intentions to adopt HIV pre-exposure prophylaxis among black men who have sex with men in Los Angeles.

PubMed

Brooks, Ronald A; Landovitz, Raphael J; Regan, Rotrease; Lee, Sung-Jae; Allen, Vincent C

2015-12-01

This study assessed perceptions of pre-exposure prophylaxis (PrEP) and their association with PrEP adoption intention among a convenience sample of 224 low socioeconomic status black men who have sex with men (BMSM) residing in Los Angeles. Participants received educational information about PrEP and completed an in-person interview. More than half (60%) of the participants indicated a high intention to adopt PrEP. Younger BMSM (18-29 years) were twice as likely to report a high intention to adopt PrEP compared to older BMSM (30+ years). Only 33% of participants were aware of PrEP and no participant had ever used PrEP. Negative perceptions were associated with a lower PrEP adoption intention and included being uncomfortable taking an HIV medicine when HIV-negative and not knowing if there are long-term side effects of taking an HIV medication. These findings suggest that BMSM may adopt PrEP but that negative perceptions may limit its uptake among this population. In order to facilitate PrEP adoption among BMSM targeted educational and community awareness programmes are needed to provide accurate information on the benefits of PrEP and to address the negative perceptions of PrEP held by local BMSM populations. © The Author(s) 2015.

A DICOM-RT based ePR radiation therapy information system for managing brain tumor patients

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Law, Maria; Huang, H. K.; Zee, C. S.; Chan, Lawrence

2005-04-01

The need for comprehensive clinical image data and relevant information in image-guided Radiation Therapy (RT) is becoming steadily apparent. Multiple standalone systems utilizing the most technological advancements in imaging, therapeutic radiation, and computerized treatment planning systems acquire key data during the RT treatment course of a patient. One example are patients treated for brain tumors of greater sizes and irregular shapes that utilize state-of-the-art RT technology to deliver pinpoint accurate radiation doses. One such system, the Cyberknife, is a radiation treatment system that utilizes image-guided information to control a multi-jointed, six degrees of freedom, robotic arm to deliver precise and required radiation dose to the tumor site of a cancer patient. The image-guided system is capable of tracking the lesion orientations with respect to the patient"s position throughout the treatment process. This is done by correlating live radiographic images with pre-operative, CT and MR imaging information to determine relative patient and tumor position repeatedly over the course of the treatment. The disparate and complex data generated by the Cyberknife system along with related data is scattered throughout the RT department compromising an efficient clinical workflow since the data crucial for a clinical decision may be time-consuming to retrieve, temporarily missing, or even lost. To address these shortcomings, the ACR-NEMA Standards Committee extended its DICOM (Digital Imaging & Communications in Medicine) Standard from Radiology to RT by ratifying seven DICOM RT objects starting in 1997. However, they are rarely used by the RT community in daily clinical operations. In the past, the research focus of an RT department has primarily been developing new protocols and devices to improve treatment process and outcomes of cancer patients with minimal effort dedicated to integration of imaging and information systems. Our research, tightly-coupling radiology and RT information systems, represents a new frontier for medical informatics research that has never been previously considered. By combining our past experience in medical imaging informatics, DICOM-RT expertise, and system integration, we propose to test our hypothesis using a brain tumor case model that a DICOM-RT electronic patient record (ePR) system can improve clinical workflow efficiency for treatment and management of patients. This RT ePR system integrated with clinical images and RT data can impact the RT department in a similar fashion as PACS has already successfully done for Radiology. As a first step, the specific treatment case of patients with brain tumors specifically patients treated with the Cyberknife system will be the initial proof of concept for the research design, implementation, evaluation, and clinical relevance.

Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men.

PubMed

Underhill, Kristen; Morrow, Kathleen M; Operario, Don; Mayer, Kenneth H

2014-02-01

The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while others perceived approval as irrelevant or less significant than other sources of information. Our results suggest that FDA approval sends a signal that directly shapes PrEP acceptability among some MSM, while indirect influences of approval may affect uptake by others. Efforts to educate MSM about PrEP can increase acceptability by incorporating information about FDA approval, and outreach strategies should consider how this information may factor into personal decisions about PrEP use.

Intelligent Transportation Systems in Work Zones - A Case Study: Work Zone Travel Time System. Reducing Congestion with the Use of a Traffic Management Contract Incentive during the Reconstruction of Arizona State Route 68

DOT National Transportation Integrated Search

2004-10-01

This case study is one in a series of documents that examines the use of Intelligent Transportation Systems (ITS) in work zones. This case study presents information gathered through interviews with key personnel on the Arizona State Route (SR) 68 pr...

[Why does the prevalence of cytopathological results of cervical cancer screening can vary significantly between two regions of Brazil?].

PubMed

Discacciati, Michelle Garcia; Barboza, Bárbara Maria Santos; Zeferino, Luiz Carlos

2014-05-01

To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Maceió and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System. Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Maceió. In Rio de Janeiro, examination at one and two year intervals predominated, while in Maceió examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Maceió were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Maceió and that of rejected samples for analysis was five times higher in Maceió when compared to Rio de Janeiro. The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Maceió. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.

Preliminary evidence of HIV seroconversion among HIV-negative men who have sex with men taking non-prescribed antiretroviral medication for HIV prevention in Miami, Florida, USA.

PubMed

Buttram, Mance E; Kurtz, Steven P

2017-04-01

Background Limited information suggests that men who have sex with men (MSM) are informally obtaining antiretroviral medication (ARVs) and using them for HIV pre-exposure prophylaxis (PrEP). Data are drawn from an on-going study examining the use of non-prescribed ARVs for PrEP. To date, 24 qualitative interviews have been conducted with HIV-negative, substance-using MSM living in Miami, Florida, USA. Data are presented from two participants who reported HIV seroconversion while using non-prescribed ARVs for PrEP. Preliminary data indicate that some young MSM: (i) lack awareness of and accurate information about the efficacious use of PrEP; (ii) obtain non-prescribed ARVs from HIV-positive sex partners and use these medications for PrEP in a way that does not provide adequate protection against HIV infection or cohere with established guidelines; and (iii) engage in multiple HIV transmission risk behaviours, including condomless anal sex and injection drug use. The informal, non-prescribed and non-medically supervised use of ARVs for HIV prevention has the potential to undermine the protective benefits of PrEP and leave men unprotected against HIV transmission and at risk for ARV resistance.

An open and configurable embedded system for EMG pattern recognition implementation for artificial arms.

PubMed

Jun Liu; Fan Zhang; Huang, He Helen

2014-01-01

Pattern recognition (PR) based on electromyographic (EMG) signals has been developed for multifunctional artificial arms for decades. However, assessment of EMG PR control for daily prosthesis use is still limited. One of the major barriers is the lack of a portable and configurable embedded system to implement the EMG PR control. This paper aimed to design an open and configurable embedded system for EMG PR implementation so that researchers can easily modify and optimize the control algorithms upon our designed platform and test the EMG PR control outside of the lab environments. The open platform was built on an open source embedded Linux Operating System running a high-performance Gumstix board. Both the hardware and software system framework were openly designed. The system was highly flexible in terms of number of inputs/outputs and calibration interfaces used. Such flexibility enabled easy integration of our embedded system with different types of commercialized or prototypic artificial arms. Thus far, our system was portable for take-home use. Additionally, compared with previously reported embedded systems for EMG PR implementation, our system demonstrated improved processing efficiency and high system precision. Our long-term goals are (1) to develop a wearable and practical EMG PR-based control for multifunctional artificial arms, and (2) to quantify the benefits of EMG PR-based control over conventional myoelectric prosthesis control in a home setting.

The Importance of Sexual History Taking for PrEP Comprehension Among Young People of Color.

PubMed

Golub, Sarit A; Gamarel, Kristi E; Lelutiu-Weinberger, Corina

2017-05-01

Despite demonstrated efficacy, uptake of pre-exposure prophylaxis (PrEP) remains low, especially among highest priority populations. This study examined four PrEP messaging factors hypothesized to impact comprehension of PrEP educational information: (1) modality (video versus in-person message delivery); (2) frame (risk versus health focus); (3) specificity (gist versus verbatim efficacy information); and (4) sexual history (administered either before or after PrEP education). We examined message comprehension among 157 young people of color (YPoC) eligible for PrEP, using a series of multiple choice questions. Overall, 65.6 % (n = 103) got all message comprehension questions correct. In multivariate analyses, engaging in a sexual history before receiving PrEP education was associated with increased odds of message comprehension (aOR 2.23; 95 % CI 1.06-4.72). This effect was even stronger among those who received PrEP education via video (aOR 3.53; 95 % CI 1.16-10.81) compared to via health educator. This research underscores the importance of sexual history-taking as part of PrEP education and clinical practice for YPoC, and suggests that engaging patients in a sexual history prior to providing them with PrEP education may be key to increasing comprehension.

Provisional Peer-Reviewed Toxicity Values for Acenaphthene

EPA Science Inventory

A Provisional Peer-Reviewed Toxicity Values (PPRTV) is defined as a toxicity value derived for use in the Superfund Program when such a value is not available from EPA’s Integrated Risk Information System (IRIS) Database. PPRTVs are developed according to a Standard Operating Pr...

[Associated Factors to non-use of Formal Health Services in the Peruvian Population: Analysis of the National Household Survey (ENAHO) 2015].

PubMed

Benites-Zapata, Vicente A; Lozada-Urbano, Michelle; Urrunaga-Pastor, Diego; Márquez-Bobadilla, Edith; Moncada-Mapelli, Enrique; Mezones-Holguín, Edward

2017-01-01

The aim of the study was to estimate the prevalence of non-use of health services (NUHS) and its associated factors using the National Household Survey (ENAHO 2015). The participants were defined as NUHS if they have presented any symptoms, discomfort, illness, relapse of chronic illness or accident during the last month and did not go to the health services. 35036 participants were analyzed; the prevalence of NUHS was 53,9%. NUHS was higher in the coastal region (adjusted Prevalence Ratio [aPR]=1.24;95%CI:1.17-1.31), highlands (aPR=1.38; 95%CI: 1.31-1.46) and jungle (aPR=1.25,95%CI:1.18-1.33) compared to Lima. Likewise, there were a higher prevalence of NUHS in participants without health insurance (aPR=1.59;95%CI:1.52-1.66) and those affiliated to Ministry of Health insurance (aPR=1.16;95%CI:1.11-1.22) compared to those affiliated to Social Security. More than half of the participants suffered from NUHS, which was associated with geographical and health system conditions. It is required evidenced-informed public policies to improve this situation.

Opt-out HIV testing of inmates in North Carolina prisons: Factors associated with not wanting a test and not knowing they were tested

PubMed Central

Grodensky, Catherine A.; Rosen, David L.; Hino, Sayaka; Golin, Carol E.; Wohl, David A.

2017-01-01

Opt-out HIV testing is recommended for correctional settings but may occur without inmates’ knowledge or against their wishes. Through surveying inmates receiving opt-out testing in a large prison system, we estimated the proportion unaware of being tested or not wanting a test, and associations (prevalence ratios [PRs]) with inmate characteristics. Of 871 tested, 11.8% were unknowingly tested and 10.8% had unwanted tests. Not attending an educational HIV course (PR=2.34, 95% CI 1.47–3.74), lower HIV knowledge (PR=0.95, 95% CI 0.91–0.98), and thinking testing is not mandatory (PR=9.84, 95% CI 4.93–19.67) were associated with unawareness of testing. No prior incarcerations (PR=1.59, 95% CI 1.03–2.46) and not using crack/cocaine recently (PR=2.37, 95% CI 1.21–4.64) were associated with unwanted testing. Residence at specific facilities was associated with both outcomes. Increased assessment of inmate understanding and enhanced implementation are needed to ensure inmates receive full benefits of opt-out testing: being informed and tested according to their wishes. PMID:26386591

Plant Pathogenesis-Related Proteins PR-10 and PR-14 as Components of Innate Immunity System and Ubiquitous Allergens.

PubMed

Finkina, Ekaterina I; Melnikova, Daria N; Bogdanov, Ivan V; Ovchinnikova, Tatiana V

2017-01-01

Pathogenesis-related (PR) proteins are components of innate immunity system in plants. They play an important role in plant defense against pathogens. Lipid transfer proteins (LTPs) and Bet v 1 homologs comprise of two separate families of PR-proteins. Both LTPs (PR-14) and Bet v 1 homologs (PR-10) are multifunctional small proteins involving in plant response to abiotic and biotic stress conditions. The representatives of these PR-protein families do not show any sequence similarity but have other common biochemical features such as low molecular masses, the presence of hydrophobic cavities, ligand binding properties, and antimicrobial activities. Besides, many members of PR-10 and PR-14 families are ubiquitous plant panallergens which are able to cause sensitization of human immune system and crossreactive allergic reactions to plant food and pollen. This review is aimed at comparative analysis of structure-functional and allergenic properties of the PR-10 and PR-14 families, as well as prospects for their medicinal application. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians.

PubMed

Palummieri, Antonio; De Carli, Gabriella; Rosenthal, Éric; Cacoub, Patrice; Mussini, Cristina; Puro, Vincenzo

2017-11-28

Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices.

Evaluation of critical distances for energy transfer between Pr{sup 3+} and Ce{sup 3+} in yttrium aluminium garnet

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

Zeng, Peng; Wei, Xiantao; Yin, Min

A series of Pr{sup 3+}/Ce{sup 3+} doped yttrium aluminium garnet (Y{sub 3}Al{sub 5}O{sub 12} or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr{sup 3+} and Ce{sup 3+} for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr{sup 3+}/Ce{sup 3+} were measured and analyzed, and it revealed that the reabsorption between Pr{sup 3+} and Ce{sup 3+} was so weak that it can be ignored, and the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{submore » 2}) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr{sup 3+} state with a Ce{sup 3+} ion, the optimal distance of Ce{sup 3+} from Pr{sup 3+} was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y{sup 3+} sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr{sup 3+}/Ce{sup 3+} doped YAG and other similar systems.« less

Swept-source based, single-shot, multi-detectable velocity range Doppler optical coherence tomography

PubMed Central

Meemon, Panomsak; Rolland, Jannick P.

2010-01-01

Phase-Resolved Doppler Optical Coherence Tomography (PR-DOCT) allows visualization and characterization of the location, direction, velocity, and profile of flow activity embedded in a static sample structure. The detectable Velocity Dynamic Range (VDR) of each particular PR-DOCT system is governed by a detectable Doppler phase shift, a flow angle, and an acquisition time interval used to determine the Doppler phase shift. In general, the lower boundary of the detectable Doppler phase shift is limited by the phase stability of the system, while the upper boundary is limited by the π phase ambiguity. For a given range of detectable Doppler phase shift, shortening the acquisition duration will increase not only the maximum detectable velocity but unfortunately also the minimum detectable velocity, which may lead to the invisibility of a slow flow. In this paper, we present an alternative acquisition scheme for PR-DOCT that extends the lower limit of the velocity dynamic range, while maintaining the maximum detectable velocity, hence increasing the overall VDR of PR-DOCT system. The essence of the approach is to implement a technique of multi-scale measurement to simultaneously acquire multiple VDRs in a single measurement. We demonstrate an example of implementation of the technique in a dual VDR DOCT, where two Doppler maps having different detectable VDRs were simultaneously detected, processed, and displayed in real time. One was a fixed VDR DOCT capable of measuring axial velocity of up to 10.9 mm/s without phase unwrapping. The other was a variable VDR DOCT capable of adjusting its detectable VDR to reveal slow flow information down to 11.3 μm/s. The technique is shown to effectively extend the overall detectable VDR of the PR-DOCT system. Examples of real time Doppler imaging of an African frog tadpole are demonstrated using the dual-VDR DOCT system. PMID:21258521

Are Centers for Disease Control and Prevention Guidelines for Preexposure Prophylaxis Specific Enough? Formulation of a Personalized HIV Risk Score for Pre-Exposure Prophylaxis Initiation.

PubMed

Beymer, Matthew R; Weiss, Robert E; Sugar, Catherine A; Bourque, Linda B; Gee, Gilbert C; Morisky, Donald E; Shu, Suzanne B; Javanbakht, Marjan; Bolan, Robert K

2017-01-01

Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying PrEP candidates may not be specific enough to identify gay, bisexual, and other men who have sex with men (MSM) at the highest risk for HIV infection. We created an HIV risk score for HIV-negative MSM based on Syndemics Theory to develop a more targeted criterion for assessing PrEP candidacy. Behavioral risk assessment and HIV testing data were analyzed for HIV-negative MSM attending the Los Angeles LGBT Center between January 2009 and June 2014 (n = 9481). Syndemics Theory informed the selection of variables for a multivariable Cox proportional hazards model. Estimated coefficients were summed to create an HIV risk score, and model fit was compared between our model and CDC guidelines using the Akaike Information Criterion and Bayesian Information Criterion. Approximately 51% of MSM were above a cutpoint that we chose as an illustrative risk score to qualify for PrEP, identifying 75% of all seroconverting MSM. Our model demonstrated a better overall fit when compared with the CDC guidelines (Akaike Information Criterion Difference = 68) in addition to identifying a greater proportion of HIV infections. Current CDC PrEP guidelines should be expanded to incorporate substance use, partner-level, and other Syndemic variables that have been shown to contribute to HIV acquisition. Deployment of such personalized algorithms may better hone PrEP criteria and allow providers and their patients to make a more informed decision prior to PrEP use.

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study.

PubMed

Storholm, Erik D; Volk, Jonathan E; Marcus, Julia L; Silverberg, Michael J; Satre, Derek D

2017-08-01

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20-35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants' risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

The Emerging Role of the Data Base Manager. Report No. R-1253-PR.

ERIC Educational Resources Information Center

Sawtelle, Thomas K.

The Air Force Logistics Command (AFLC) is revising and enhancing its data-processing capabilities with the development of a large-scale, multi-site, on-line, integrated data base information system known as the Advanced Logistics System (ALS). A data integrity program is to be built around a Data Base Manager (DBM), an individual or a group of…

Subway Environmental Design Handbook, Volume II, Subway Environment Simulation Computer Program, Version 4, Part 1, User's Manual

DOT National Transportation Integrated Search

1975-10-01

This document forms part of the Subway Environmental Design Handbook. It contains the background information and instructions to enable an engineer to perform an analysis of a subway system by using the Subway Environment Simulation (SES) computer pr...

A multimedia electronic patient record (ePR) system to improve decision support in pre- and rehabilitation through clinical and movement analysis

NASA Astrophysics Data System (ADS)

Liu, Brent; Documet, Jorge; McNitt-Gray, Sarah; Requejo, Phil; McNitt-Gray, Jill

2011-03-01

Clinical decisions for improving motor function in patients both with disability as well as improving an athlete's performance are made through clinical and movement analysis. Currently, this analysis facilitates identifying abnormalities in a patient's motor function for a large amount of neuro-musculoskeletal pathologies. However definitively identifying the underlying cause or long-term consequences of a specific abnormality in the patient's movement pattern is difficult since this requires information from multiple sources and formats across different times and currently relies on the experience and intuition of the expert clinician. In addition, this data must be persistent for longitudinal outcomes studies. Therefore a multimedia ePR system integrating imaging informatics data could have a significant impact on decision support within this clinical workflow. We present the design and architecture of such an ePR system as well as the data types that need integration in order to develop relevant decision support tools. Specifically, we will present two data model examples: 1) A performance improvement project involving volleyball athletes and 2) Wheelchair propulsion evaluation of patients with disabilities. The end result is a new frontier area of imaging informatics research within rehabilitation engineering and biomechanics.

Phase diagram of the Pr-Mn-O system in composition-temperature-oxygen pressure coordinates

NASA Astrophysics Data System (ADS)

Vedmid', L. B.; Yankin, A. M.; Fedorova, O. M.; Kozin, V. M.

2016-05-01

The phase relations in the Pr-Mn-O system were studied by the static method at lowered oxygen pressure in combination with thermal analysis and high-temperature X-ray diffraction. The equilibrium oxygen pressure in dissociation of PrMn2O5 and PrMnO3 was measured, and the thermodynamic characteristics of formation of these compounds from elements were calculated. The P- T- x phase diagram of the Pr-Mn-O system was constructed in the "composition-oxygen pressure-temperature" coordinates.

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation: A qualitative study.

PubMed

Bil, Janneke P; van der Veldt, Wendy M; Prins, Maria; Stolte, Ineke G; Davidovich, Udi

2016-09-01

Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling.

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation

PubMed Central

Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi

2016-01-01

Abstract Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM). Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach. Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients’ medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support. To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling. PMID:27684827

Introduction to Quantum Information/Computing

DTIC Science & Technology

2005-06-01

SUBTITLE INTRODUCTION TO QUANTUM INFORMATION/COMPUTING 6. AUTHOR( S ) Peter J. Costianes 5. FUNDING NUMBERS C - N/A PE - 62702F PR...concept is an important concept in Quantum Mechanics and will be further applied later in this report. 2.8 Discrete Orthonormal Bases in F. 2.8.1...index i in defining the coordinates of the wavevector. Many quantum systems may be represented by both a continuous and discrete set of bases

Réunion publique HR

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

None

2010-04-30

Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanéemore » de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie CatherinHead, Human Resources Department« less

Réunion publique HR

ScienceCinema

None

2017-12-09

Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie CatherinHead, Human Resources Department

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

PubMed

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC scores for any S1PR (cytoplasmic or nuclear) between benign and malignant changes. This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

PubMed Central

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M.; Zhou, Xinchun

2014-01-01

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC score of any S1PR (cytoplasmic or nuclear) between benign and malignant changes. Conclusion This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. PMID:25084322

HIV-1 Protease in the Fission Yeast Schizosaccharomyces pombe.

PubMed

Benko, Zsigmond; Elder, Robert T; Li, Ge; Liang, Dong; Zhao, Richard Y

2016-01-01

HIV-1 protease (PR) is an essential viral enzyme. Its primary function is to proteolyze the viral Gag-Pol polyprotein for production of viral enzymes and structural proteins and for maturation of infectious viral particles. Increasing evidence suggests that PR cleaves host cellular proteins. However, the nature of PR-host cellular protein interactions is elusive. This study aimed to develop a fission yeast (Schizosaccharomyces pombe) model system and to examine the possible interaction of HIV-1 PR with cellular proteins and its potential impact on cell proliferation and viability. A fission yeast strain RE294 was created that carried a single integrated copy of the PR gene in its chromosome. The PR gene was expressed using an inducible nmt1 promoter so that PR-specific effects could be measured. HIV-1 PR from this system cleaved the same indigenous viral p6/MA protein substrate as it does in natural HIV-1 infections. HIV-1 PR expression in fission yeast cells prevented cell proliferation and induced cellular oxidative stress and changes in mitochondrial morphology that led to cell death. Both these PR activities can be prevented by a PR-specific enzymatic inhibitor, indinavir, suggesting that PR-mediated proteolytic activities and cytotoxic effects resulted from enzymatic activities of HIV-1 PR. Through genome-wide screening, a serine/threonine kinase, Hhp2, was identified that suppresses HIV-1 PR-induced protease cleavage and cell death in fission yeast and in mammalian cells, where it prevented PR-induced apoptosis and cleavage of caspase-3 and caspase-8. This is the first report to show that HIV-1 protease is functional as an enzyme in fission yeast, and that it behaves in a similar manner as it does in HIV-1 infection. HIV-1 PR-induced cell death in fission yeast could potentially be used as an endpoint for mechanistic studies, and this system could be used for developing a high-throughput system for drug screenings.

Yeast: A Research Organism for Teaching Genetics.

ERIC Educational Resources Information Center

Manney, Thomas R.; Manney, Monta L.

1992-01-01

Explains why laboratory strains of bakers yeast, Saccharomyces cerevisiae, are particularly suited for classroom science activities. Describes the sexual life cycle of yeast and the genetic system with visible mutations. Presents an overview of activities that can be done with yeast and gives a source for teachers to obtain more information. (PR)

FCRD Advanced Reactor (Transmutation) Fuels Handbook

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

Janney, Dawn Elizabeth; Papesch, Cynthia Ann

2016-09-01

Transmutation of minor actinides such as Np, Am, and Cm in spent nuclear fuel is of international interest because of its potential for reducing the long-term health and safety hazards caused by the radioactivity of the spent fuel. One important approach to transmutation (currently being pursued by the DOE Fuel Cycle Research & Development Advanced Fuels Campaign) involves incorporating the minor actinides into U-Pu-Zr alloys, which can be used as fuel in fast reactors. U-Pu-Zr alloys are well suited for electrolytic refining, which leads to incorporation rare-earth fission products such as La, Ce, Pr, and Nd. It is, therefore, importantmore » to understand not only the properties of U-Pu-Zr alloys but also those of U-Pu-Zr alloys with concentrations of minor actinides (Np, Am) and rare-earth elements (La, Ce, Pr, and Nd) similar to those in reprocessed fuel. In addition to requiring extensive safety precautions, alloys containing U, Pu, and minor actinides (Np and Am) are difficult to study for numerous reasons, including their complex phase transformations, characteristically sluggish phasetransformation kinetics, tendency to produce experimental results that vary depending on the histories of individual samples, rapid oxidation, and sensitivity to contaminants such as oxygen in concentrations below a hundred parts per million. Although less toxic, rare-earth elements such as La, Ce, Pr, and Nd are also difficult to study for similar reasons. Many of the experimental measurements were made before 1980, and the level of documentation for experimental methods and results varies widely. It is, therefore, not surprising that little is known with certainty about U-Pu-Zr alloys, particularly those that also contain minor actinides and rare-earth elements. General acceptance of results commonly indicates that there is only a single measurement for a particular property. This handbook summarizes currently available information about U, Pu, Zr, Np, Am, La, Ce, Pr, and Nd and alloys of two or three of these elements. It contains information about phase diagrams and related information (including phases and phase transformations); heat capacity, entropy, and enthalpy; thermal expansion; and thermal conductivity and diffusivity. In addition to presenting information about materials properties, the handbook attempts to provide information about how well the property is known and how much variation exists between measurements. Although it includes some results from models, its primary focus is experimental data. The Handbook is organized in two sections: one with information about the U-Pu-Zr ternary and one with information about other elements and binary and vi ternary alloys in the U-Np-Pu-Am-La-Ce-Pr-Nd-Zr system. Within each section, information about elements is presented first, followed by information about binary alloys, then information about ternary alloys. The order in which the elements in each alloy are mentioned follows the order in the first sentence of this paragraph. Much of the information on the U-Pu-Zr system repeats information from the FCRD Transmutation Fuels Handbook 2015. Most of the other data has been published elsewhere (although scattered throughout numerous references, some quite obscure); however, some data from Idaho National Laboratory is presented here for the first time. As the FCRD programmatic mission evolves, future editions of this handbook will begin to include other advanced reactor fuel designs and compositions. Hence, the title of the handbook will transition to the Advanced Reactor Fuels Handbook.« less

Organization of the Drosophila larval visual circuit

PubMed Central

Gendre, Nanae; Neagu-Maier, G Larisa; Fetter, Richard D; Schneider-Mizell, Casey M; Truman, James W; Zlatic, Marta; Cardona, Albert

2017-01-01

Visual systems transduce, process and transmit light-dependent environmental cues. Computation of visual features depends on photoreceptor neuron types (PR) present, organization of the eye and wiring of the underlying neural circuit. Here, we describe the circuit architecture of the visual system of Drosophila larvae by mapping the synaptic wiring diagram and neurotransmitters. By contacting different targets, the two larval PR-subtypes create two converging pathways potentially underlying the computation of ambient light intensity and temporal light changes already within this first visual processing center. Locally processed visual information then signals via dedicated projection interneurons to higher brain areas including the lateral horn and mushroom body. The stratified structure of the larval optic neuropil (LON) suggests common organizational principles with the adult fly and vertebrate visual systems. The complete synaptic wiring diagram of the LON paves the way to understanding how circuits with reduced numerical complexity control wide ranges of behaviors.

Better Demand Signal, Better Decisions? Evaluation of Big Data in a Licensed Remanufacturing Supply Chain with Environmental Risk Considerations.

PubMed

Niu, Baozhuang; Zou, Zongbao

2017-08-01

Big data ability helps obtain more accurate demand signal. However, is better demand signal always beneficial for the supply chain parties? To answer this question, we investigate a remanufacturing supply chain (RSC), where demand uncertainty is significant, and the value to reduce environmental risk is large. Specifically, we focus on a licensed RSC comprising an original equipment manufacturer (OEM) and a third-party remanufacturer (3PR). The latter pays a unit license fee to the former, and can be risk averse to the demand of remanufactured products. We show that the OEM and the risk-neutral 3PR always have incentives to improve their big data abilities to increase their profits. However, when the 3PR is risk averse, big data might hurt its profit: the value of big data is positive if its demand signal accuracy is sufficiently low. Interestingly, we find that while information sharing hurts the 3PR, it benefits the OEM as well as the supply chain. Thus, if costly information sharing is allowed, a win-win situation can be achieved. We also find that information sharing generates more valuation when the 3PR is risk averse than that when the 3PR is risk neutral. More importantly, we find that the 3PR's risk attitude and demand signal accuracy can significantly mitigate the negative environmental impact (measured by the amount of the waste): (1) the more risk neutral the 3PR is, the better the environment is; (2) the more accurate demand signal is, the better the environment is. © 2017 Society for Risk Analysis.

A thermal and chemical degradation approach to decipher pristane and phytane precursors in sedimentary organic matter

USGS Publications Warehouse

Koopmans, M.P.; Rijpstra, W.I.C.; Klapwijk, M.M.; De Leeuw, J. W.; Lewan, M.D.; Sinninghe, Damste J.S.

1999-01-01

A thermal and chemical degradation approach was followed to determine the precursors of pristane (Pr) and phytane (Ph) in samples from the Gessoso-solfifera, Ghareb and Green River Formations. Hydrous pyrolysis of these samples yields large amounts of Pr and Ph carbon skeletons, indicating that their precursors are predominantly sequestered in high-molecular-weight fractions. However, chemical degradation of the polar fraction and the kerogen of the unheated samples generally does not release large amounts of Pr and Ph. Additional information on the precursors of Pr and Ph is obtained from flash pyrolysis analyses of kerogens and residues after hydrous pyrolysis and after chemical degradation. Multiple precursors for Pr and Ph are recognised in these three samples. The main increase of the Pr/Ph ratio with increasing maturation temperature, which is associated with strongly increasing amounts of Pr and Ph, is probably due to the higher amount of precursors of Pr compared to Ph, and not to the different timing of generation of Pr and Ph.A thermal and chemical degradation approach was followed to determine the precursors of pristane (Pr) and phytane (Ph) in samples from the Gessoso-solfifera, Ghareb and Green River Formations. Hydrous pyrolysis of these samples yields large amounts of Pr and Ph carbon skeletons, indicating that their precursors are predominantly sequestered in high-molecular-weight fractions. However, chemical degradation of the polar fraction and the kerogen of the unheated samples generally does not release large amounts of Pr and Ph. Additional information on the precursors of Pr and Ph is obtained from flash pyrolysis analyses of kerogens and residues after hydrous pyrolysis and after chemical degradation. Multiple precursors for Pr and Ph are recognised in these three samples. The main increase of the Pr/Ph ratio with increasing maturation temperature, which is associated with strongly increasing amounts of Pr and Ph, is probably due to the higher amount of precursors of Pr compared to Ph, and not to the different timing of generation of Pr and Ph.

Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

PubMed

De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

2015-04-01

Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acceptability of HIV Pre-Exposure Prophylaxis (PrEP) and Implementation Challenges Among Men Who Have Sex with Men in India: A Qualitative Investigation.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Varghese, Jarvis; Nelson, Ruban; Bharat, Shalini

2015-10-01

This qualitative study explored the acceptability of HIV pre-exposure prophylaxis (PrEP) among MSM in India, and identified facilitators and barriers to future PrEP uptake. In 2014, we conducted 10 focus groups (n=61) among a purposive sample of diverse MSM recruited through community-based organizations in Chennai and Mumbai, and 10 key informant interviews with community leaders and health care providers. Participants' mean age was 26.1 years (SD 4.8); 62% completed secondary education, and 42% engaged in sex work. No focus group participants had heard of PrEP, but once explained, most reported they would likely use it. PrEP was alternately perceived as a 'back-up plan', a condom substitute, or a burden with concurrent condom use. Facilitators were potential for covert use, sex without condoms, and anxiety-less sex. Potential barriers emerged around stigma associated with PrEP use, fear of disclosures to one's family, wife, or male steady partner, and being labeled as HIV-positive or promiscuous by peers. Preferences emerged for intermittent rather than daily PrEP use, injectable PrEP, and free or subsidized access through community organizations or government hospitals. Key informants expressed additional concerns about risk compensation, non-adherence, and impact on ART availability for treatment. Demonstration projects are needed in India to support PrEP implementation tailored for at-risk MSM. Educational interventions for MSM should address concerns about PrEP effectiveness, side effects, and mitigate risk compensation. Community engagement may facilitate broad acceptability and challenge stigma around PrEP use. Importantly, provision of free or subsidized PrEP is necessary to making implementation feasible among low socioeconomic status MSM in India.

Improving Army Information Technology Asset Visibility

DTIC Science & Technology

2012-03-09

periodically certify their APMS information is accurate and complete. Finally, related to AR 25-1 is Department of the Army Pamphlet 25-1-1 (DA PAM 25...Resource Manager, who certified funds were available to cover the request. Next, the GFEBS PR was routed to the servicing Contracting Office for review...it was certified by the Defense Business Systems Management Committee (DBSMC), then it must be registered and the data on it maintained in APMS. An

76 FR 63628 - Preliminary Damage Assessment for Individual Assistance Operations Manual (9327.2-PR)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

...] Preliminary Damage Assessment for Individual Assistance Operations Manual (9327.2-PR) AGENCY: Federal... Individual Assistance Operations Manual (9327.2-PR). DATES: Comments must be received by November 14, 2011...., Washington, DC 20472-3100. FOR FURTHER INFORMATION CONTACT: Michael M. Grimm, Individual Assistance Director...

Interspecific Sex in Grass Smuts and the Genetic Diversity of Their Pheromone-Receptor System

PubMed Central

Kellner, Ronny; Vollmeister, Evelyn; Feldbrügge, Michael; Begerow, Dominik

2011-01-01

The grass smuts comprise a speciose group of biotrophic plant parasites, so-called Ustilaginaceae, which are specifically adapted to hosts of sweet grasses, the Poaceae family. Mating takes a central role in their life cycle, as it initiates parasitism by a morphological and physiological transition from saprobic yeast cells to pathogenic filaments. As in other fungi, sexual identity is determined by specific genomic regions encoding allelic variants of a pheromone-receptor (PR) system and heterodimerising transcription factors. Both operate in a biphasic mating process that starts with PR–triggered recognition, directed growth of conjugation hyphae, and plasmogamy of compatible mating partners. So far, studies on the PR system of grass smuts revealed diverse interspecific compatibility and mating type determination. However, many questions concerning the specificity and evolutionary origin of the PR system remain unanswered. Combining comparative genetics and biological approaches, we report on the specificity of the PR system and its genetic diversity in 10 species spanning about 100 million years of mating type evolution. We show that three highly syntenic PR alleles are prevalent among members of the Ustilaginaceae, favouring a triallelic determination as the plesiomorphic characteristic of this group. Furthermore, the analysis of PR loci revealed increased genetic diversity of single PR locus genes compared to genes of flanking regions. Performing interspecies sex tests, we detected a high potential for hybridisation that is directly linked to pheromone signalling as known from intraspecies sex. Although the PR system seems to be optimised for intraspecific compatibility, the observed functional plasticity of the PR system increases the potential for interspecific sex, which might allow the hybrid-based genesis of newly combined host specificities. PMID:22242007

Misunderstanding of Pre-Exposure Prophylaxis Use Among Men Who Have Sex with Men: Public Health and Policy Implications.

PubMed

Kurtz, Steven P; Buttram, Mance E

2016-12-01

Street markets in antiretroviral medications for HIV have been documented, but sources of demand are not well understood. We report unexpected findings from qualitative research suggesting that some demand is for informal pre-exposure prophylaxis (PrEP). Focus groups with young men who have sex with men (N = 31) yielded information on their understanding and use of PrEP. Of those who had heard of it, few understood PrEP to be a physician-prescribed regimen; most believed it to be a pill taken before and/or after sex and acquired on the street or through HIV-positive friends. Implications for PrEP rollout and public health policy are discussed.

The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study.

PubMed

Carere, Deanna Alexis; VanderWeele, Tyler; Moreno, Tanya A; Mountain, Joanna L; Roberts, J Scott; Kraft, Peter; Green, Robert C

2015-10-15

Direct access to genomic information has the potential to transform cancer risk counseling. We measured the impact of direct-to-consumer genomic risk information on changes to perceived risk (ΔPR) of breast, prostate, colorectal and lung cancer among personal genomic testing (PGT) customers. We hypothesized that ΔPR would reflect directionality of risk estimates, attenuate with time, and be modified by participant characteristics. Pathway Genomics and 23andMe customers were surveyed prior to receiving PGT results, and 2 weeks and 6 months post-results. For each cancer, PR was measured on a 5-point ordinal scale from "much lower than average" to "much higher than average." PGT results, based on genotyping of common genetic variants, were dichotomized as elevated or average risk. The relationship between risk estimate and ΔPR was evaluated with linear regression; generalized estimating equations modeled this relationship over time. With the exception of lung cancer (for which ΔPR was positive regardless of result), elevated risk results were significantly associated with positive ΔPR, and average risk results with negative ΔPR (e.g., prostate cancer, 2 weeks: least squares-adjusted ΔPR = 0.77 for elevated risk versus -0.21 for average risk; p-valuedifference < 0.0001) among 1154 participants. Large changes were rare: for each cancer, <4 % of participants overall reported a ΔPR of ±3 or more units. Effect modification by age, cancer family history, and baseline interest was observed for breast, colorectal, and lung cancer, respectively. A pattern of decreasing impact on ΔPR over time was consistently observed, but this trend was significant only in the case of colorectal cancer. We have quantified the effect on consumer risk perception of returning genetic-based cancer risk information directly to consumers without clinician mediation. Provided via PGT, this information has a measurable but modest effect on perceived cancer risk, and one that is in some cases modified by consumers' non-genetic risk context. Our observations of modest marginal effect sizes, infrequent extreme changes in perceived risk, and a pattern of diminishing impact with time, suggest that the ability of PGT to effect changes to cancer screening and prevention behaviors may be limited by relatively small changes to perceived risk.

L'émergence de la thérapeutique de précision: de nouveaux défis et de nouvelles possibilités pour les leaders en santé du Canada.

PubMed

Slater, Jim; Shields, Laura; Racette, Ray J; Juzwishin, Donald; Coppes, Max

2015-11-01

À l'ère de la médecine personnalisée et de la médecine de précision, l'approche envers les soins est en rapide mutation. Les cliniciens exigent de plus en plus d'information génétique et moléculaire et les patients s'attendent à la fournir pour la prévention, le dépistage, le diagnostic, le pronostic, la promotion de la santé et le traitement d'un nombre croissant de maladies. Les leaders en santé canadiens doivent comprendre les changements nécessaires liés à ces technologies perturbantes et ouvrir la voie. Le présent article s'attarde sur la thérapeutique de précision, mais contient également de l'information générale sur les concepts et la terminologie liés à la médecine personnalisée et à la médecine de précision. Il explore également le leadership en santé canadien et les problèmes liés au système qui peuvent nuire à leur mise en œuvre. L'article vise à inspirer, informer et mobiliser les leaders en santé canadiens à amorcer un dialogue sur les transformations nécessaires pour préparer le système de santé à profiter des bienfaits de la thérapeutique de précision. © 2015 Collège canadien des leaders en santé

Weather-Corrected Performance Ratio

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

Dierauf, T.; Growitz, A.; Kurtz, S.

Photovoltaic (PV) system performance depends on both the quality of the system and the weather. One simple way to communicate the system performance is to use the performance ratio (PR): the ratio of the electricity generated to the electricity that would have been generated if the plant consistently converted sunlight to electricity at the level expected from the DC nameplate rating. The annual system yield for flat-plate PV systems is estimated by the product of the annual insolation in the plane of the array, the nameplate rating of the system, and the PR, which provides an attractive way to estimatemore » expected annual system yield. Unfortunately, the PR is, again, a function of both the PV system efficiency and the weather. If the PR is measured during the winter or during the summer, substantially different values may be obtained, making this metric insufficient to use as the basis for a performance guarantee when precise confidence intervals are required. This technical report defines a way to modify the PR calculation to neutralize biases that may be introduced by variations in the weather, while still reporting a PR that reflects the annual PR at that site given the project design and the project weather file. This resulting weather-corrected PR gives more consistent results throughout the year, enabling its use as a metric for performance guarantees while still retaining the familiarity this metric brings to the industry and the value of its use in predicting actual annual system yield. A testing protocol is also presented to illustrate the use of this new metric with the intent of providing a reference starting point for contractual content.« less

Economic evaluation of HIV pre-exposure prophylaxis strategies: protocol for a methodological systematic review and quantitative synthesis.

PubMed

Thavorn, Kednapa; Kugathasan, Howsikan; Tan, Darrell H S; Moqueet, Nasheed; Baral, Stefan D; Skidmore, Becky; MacFadden, Derek; Simkin, Anna; Mishra, Sharmistha

2018-03-15

Pre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes. We will systematically search electronic databases (MEDLINE, Embase) and the gray literature. We will include economic evaluation studies that assess both costs and health outcomes of PrEP in HIV-uninfected individuals, without restricting language or year of publication. Two reviewers will independently screen studies using predefined inclusion criteria, extract data, and assess methodological quality using the Philips checklist, Second Panel on the Cost-effectiveness of Health and Medicines, and the International Society for Pharmacoeconomics and Outcomes Research recommendations. Outcomes of interest include incremental costs and outcomes in natural units or utilities, cost-effectiveness ratios, and net monetary benefit. We will perform descriptive and quantitative syntheses using sensitivity analyses of outcomes by population subgroups, HIV epidemic settings, study designs, baseline intervention contexts, key parameter inputs and assumptions, type of outcomes, economic perspectives, and willingness to pay values. Findings will guide future economic evaluation of PrEP strategies in terms of methodological and knowledge gaps, and will inform decisions on the efficient integration of PrEP into public health programs across epidemiologic and health system contexts. PROSPERO CRD42016038440 .

Intelligent ePR system for evidence-based research in radiotherapy: proton therapy for prostate cancer.

PubMed

Le, Anh H; Liu, Brent; Schulte, Reinhard; Huang, H K

2011-11-01

Proton therapy (PT) utilizes high energy particle proton beam to kill cancer cells at the target region for target cancer therapy. Due to the physical properties of the proton beam, PT delivers dose with higher precision and no exit dose compared to conventional radiotherapy. In PT, patient data are distributed among multiple systems, a hindrance to research on efficacy and effectiveness. A data mining method and a treatment plan navigator utilizing the infrastructure and data repository of a PT electronic patient record (ePR) was developed to minimize radiation toxicity and improve outcomes in prostate cancer treatment. MATERIALS/METHOD(S): The workflow of a proton therapy treatment in a radiation oncology department was reviewed, and a clinical data model and data flow were designed. A prototype PT ePR system with DICOM compliance was developed to manage prostate cancer patient images, treatment plans, and related clinical data. The ePR system consists of four main components: (1) Data Gateway; (2) ePR Server; (3) Decision Support Tools; and (4) Visualization and Display Tools. Decision support and visualization tools are currently developed based on DICOM images, DICOM-RT and DICOM-RT-ION objects data from prostate cancer patients treated with hypofractionation protocol proton therapy were used for evaluating ePR system effectiveness. Each patient data set includes a set of computed tomography (CT) DICOM images and four DICOM-RT and RT-ION objects. In addition, clinical outcomes data collected from PT cases were included to establish a knowledge base for outcomes analysis. A data mining search engine and an intelligent treatment plan navigator (ITPN) were developed and integrated with the ePR system. Evaluation was based on a data set of 39 PT patients and a hypothetical patient. The ePR system was able to facilitate the proton therapy workflow. The PT ePR system was feasible for prostate cancer patient treated with hypofractionation protocol in proton therapy. This ePR system improves efficiency in data collection and integration to facilitate outcomes analysis.

Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

PubMed

Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E

2017-05-01

Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

PubMed

Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

2015-09-01

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

Thermodynamic assessment of the Pr-O system

DOE PAGES

McMurray, Jake W.

2015-12-24

We found that the Calphad method was used to perform a thermodynamic assessment of the Pr–O system. Compound energy formalism representations were developed for the fluorite α-PrO 2–x and bixbyite σ-Pr 3 O 5 ± x solid solutions while the two-sublattice liquid model was used to describe the binary melt. The series of phases between Pr 2 O 3 and PrO 2 were taken to be stoichiometric. Moreover, the equilibrium oxygen pressure, phase equilibria, and enthalpy data were used to optimize the adjustable parameters of the models for a self-consistent representation of the thermodynamic behavior of the Pr–O system frommore » 298 K to melting.« less

Comprehensive Study of Pr-Doped GdBa2Cu3O7 - y System

NASA Astrophysics Data System (ADS)

Yamani, Z.; Akhavan, M.

1997-09-01

An extensive study of the magnetic, electrical transport, and structural properties of the normal and superconducting states of Gd1 - xPrxBa2Cu3O7 - y (GdPr-123) is presented. Ceramic compounds have been synthesized by the solid state reaction technique, and characterized by XRD, SEM, TGA, and DT techniques. The parent compound GdBa2Cu3O7 - y (Gd-123) is a high-Tc superconductor and the endpoint compound, PrBa2Cu3O7 - y (Pr-123) is a magnetic insulator, both having the crystal structures isomorphic to the 123 phase structure. The superconducting transition temperature is reduced with increasing Pr content in a non-linear manner, in contrast to the Abrikosov-Gorkov pair breaking theory. A metal-insulator transition is observed at the critical Pr content, xcr 0.45, at which superconductivity completely disappears. Magnetic susceptibility measurements show that the nominal Pr valence is 3.86+, independent of the Pr content. The metal-insulator transition in this system is similar to that in the oxygen-deficient RBa2Cu3O7 - y (R-123) system. Based on this resemblance, we suggest that Pr doping reduces the carrier concentration (either by hole filling/localization or changes in the band structure) similar to the deoxygenated case. Hence, the environment surrounding the Cu-O layers is important to high-Tc superconductivity (HTSC). In this sense, HTSC cannot completely be two dimensional feature. A chain-plane correlation (CPC) effect is plausible. The normal state conduction mechanism has been interpreted by the quantum percolation theory based on localized states. Localization is probably caused by the Pr valence fluctuations in the GdPr-123 system.

Traditional and pyramidal resistance training systems improve muscle quality and metabolic biomarkers in older women: A randomized crossover study.

PubMed

Ribeiro, Alex S; Schoenfeld, Brad J; Souza, Mariana F; Tomeleri, Crisieli M; Venturini, Danielle; Barbosa, Décio S; Cyrino, Edilson S

2016-06-15

The purpose of this study was to compare the effect of RT performed in a pyramid (PR) and traditional (TD) straight set training system on muscle quality and metabolic biomarkers in older women. Twenty-five physically independent older women (67.6±5.1years, 65.9±11.1kg, 154.7±5.8cm) performed a RT program in TD and PR training systems in a balanced crossover design. Measurements of muscle quality, serum levels of C-reactive protein (CRP), glucose (GLU), total cholesterol, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides (TG) were obtained at different moments. The TD program consisted of 3 sets of 8-12 repetitions maximum (RM) with a constant weight for the 3 sets, whereas the PR training consisted of 3 sets of 12/10/8 RM with incremental weight for each set. The training was performed in 2 phases of 8weeks each, with a 12-week washout period between phases. Significant (P<0.05) improvements were observed in both groups for muscle quality (TD=+8.6% vs. PR=+6.8%), GLU (TD=-4.5% vs. PR=-1.9%), TG (TD=-18.0% vs. PR=-11.7%), HDL-C (TD=+10.6 vs. PR=+7.8%), LDL-C (TD=-23.3% vs. PR=-21.0%), and CRP (TD=-19.4% vs. PR=-14.3%) with no differences between training systems. These results suggest that RT improves muscle quality and metabolic biomarkers of older women independently of the training system. Copyright © 2016 Elsevier Inc. All rights reserved.

A real-time, practical sensor fault-tolerant module for robust EMG pattern recognition.

PubMed

Zhang, Xiaorong; Huang, He

2015-02-19

Unreliability of surface EMG recordings over time is a challenge for applying the EMG pattern recognition (PR)-controlled prostheses in clinical practice. Our previous study proposed a sensor fault-tolerant module (SFTM) by utilizing redundant information in multiple EMG signals. The SFTM consists of multiple sensor fault detectors and a self-recovery mechanism that can identify anomaly in EMG signals and remove the recordings of the disturbed signals from the input of the pattern classifier to recover the PR performance. While the proposed SFTM has shown great promise, the previous design is impractical. A practical SFTM has to be fast enough, lightweight, automatic, and robust under different conditions with or without disturbances. This paper presented a real-time, practical SFTM towards robust EMG PR. A novel fast LDA retraining algorithm and a fully automatic sensor fault detector based on outlier detection were developed, which allowed the SFTM to promptly detect disturbances and recover the PR performance immediately. These components of SFTM were then integrated with the EMG PR module and tested on five able-bodied subjects and a transradial amputee in real-time for classifying multiple hand and wrist motions under different conditions with different disturbance types and levels. The proposed fast LDA retraining algorithm significantly shortened the retraining time from nearly 1 s to less than 4 ms when tested on the embedded system prototype, which demonstrated the feasibility of a nearly "zero-delay" SFTM that is imperceptible to the users. The results of the real-time tests suggested that the SFTM was able to handle different types of disturbances investigated in this study and significantly improve the classification performance when one or multiple EMG signals were disturbed. In addition, the SFTM could also maintain the system's classification performance when there was no disturbance. This paper presented a real-time, lightweight, and automatic SFTM, which paved the way for reliable and robust EMG PR for prosthesis control.

Role of Pr substitution as deoxygenation in suppression of superconductivity in GdPr-123 system

NASA Astrophysics Data System (ADS)

Yamani, Z.; Akhavan, M.

1996-02-01

Predominantly single phase polycrystalline Gd 1- xPr xBa 2Cu 3O 7- y (GdPr-123) samples with 0 ≤ x ≤ 1.0 have been prepared by standard solid state reaction technique and characterized by XRD. The electrical resistivity measurements show the suppression of superconductivity with increasing x. Two plateaus appear in the Tc versus x curve at x ≈ 0-0.05 and at x ≈ 0.15-0.25 followed by a decrease to zero at xcr ≈ 0.45, similar to the plateaus of Tc versus 7 - y curve at 7 - y ≈ 6.8 -7 and at 7 - y ≈ 6.55-6.75 in RBa 2Cu 3O 7 - y ( R-123) ( R: Y or rare earth except Ce, Pr, Pm, Tb) systems. The valency of Pr was determined by magnetization measurements in the temperature range 100 K to 250 K. This data indicates a mixed valence state for Pr ions with an effective magnetic moment μ ≈ 2.69 μB per Pr ion, which yields a valency for Pr of ≈ 3.86 +. For these systems, Tc( x) does not follow the Abrikosov-Gor'kov pair breaking theory. We suggest that the suppression of superconductivity by Pr-substitution can be explained by means of an effective increasing of the oxygen deficiency in the structure, in a similar way to what happens in an R-123 system, when 7 - y is decreased in a controlled manner. This implies that CuO 2 planes are responsible for superconductivity through the effect of chains.

Prostate cancer incidence and tumor severity in Georgia: descriptive epidemiology, racial disparity, and geographic trends.

PubMed

Wagner, Sara E; Bauer, Sarah E; Bayakly, A Rana; Vena, John E

2013-01-01

Limited research has been conducted to describe the geographical clustering and distribution of prostate cancer (PrCA) incidence in Georgia (GA). This study describes and compares the temporal and geographic trends of PrCA incidence in GA with a specific focus on racial disparities. GA Comprehensive Cancer Registry PrCA incidence data were obtained for 1998-2008. Directly standardized age-adjusted PrCA incidence rates per 100,000 were analyzed by race, stage, grade, and county. County-level hotspots of PrCA incidence were analyzed with the Getis-Ord Gi* statistic in a geographic information system; a census tract-level cluster analysis was performed with a Discrete Poisson model and implemented in SaTScan(®) software. Significant (p < 0.05) hotspots of PrCA incidence were observed in nine southwestern counties and six centrally located counties among men of both races. Six significant (p < 0.1) clusters of PrCA incidence rates were detected for men of both races in north and northwest central Georgia. When stratified by race, clusters among white and black men were similar, although centroids were slightly shifted. Most notably, a large (122 km radius) cluster in northwest central Georgia was detected only in whites, and two smaller clusters (0-32 km radii) were detected in Southwest Georgia only in black men. Clusters of high-grade and late-stage tumors were identified primarily in the northern portion of the state among men of both races. This study revealed a pattern of higher incidence and more advanced disease in northern and northwest central Georgia, highlighting geographic patterns that need more research and investigation of possible environmental determinants.

Organically Assured and Survivable Information Systems (OASIS) Technology Transition Assessment (OTTA)

DTIC Science & Technology

2004-03-01

OTTA) 6. AUTHOR(S) Mike Duren 5. FUNDING NUMBERS C - F30602-01- C -0207 PE - 63760E PR - K128 TA - 00 WU - 01 7...Force Research Laboratory (AFRL) contract F30602-01- C -0207. This report serves as the Contract Data Requirements List (CDRL) CLIN 0002, Item A004 for...Tolerant Systems (RFITS) Ranga Ramanujan , Architecture Technology Corp. (also ORA) http://www.atcor p.com Develop and document in handbook

An Analysis of Pregnancy-Related Mortality in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya

PubMed Central

Desai, Meghna; Phillips-Howard, Penelope A.; Odhiambo, Frank O.; Katana, Abraham; Ouma, Peter; Hamel, Mary J.; Omoto, Jackton; Macharia, Sheila; van Eijk, Annemieke; Ogwang, Sheila; Slutsker, Laurence; Laserson, Kayla F.

2013-01-01

Background Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth. Methods and Findings To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (p = 0.034), while less impoverished women were more likely to seek hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trend = 1.07; p = 0.3). Conclusions These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality. PMID:23874741

[Human transmissible subacute spongiform encephalopathy].

PubMed

Dormont, D

1994-05-01

Human transmissible spongiform encephalopathies (TSE) are rare chronic subacute degenerative diseases of the central nervous system (CNS) which include Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI). CJD can be either inherited or sporadic. All these diseases are always fatal. Neuropathological features are mainly constituted of neuronal vacuolisation, neuronal death, gliosis with hyperastrocytosis; plaques might be evidenced in kuru and GSS. Neither inflammatory syndrome nor demyelination is detectable. No virus like structure could be identified reproducibly. Human TSE are transmissible to non human primates and rodents. Iatrogenic CJD have been described after tissue grafting (cornea, dura mater), neurosurgery, electrophysiology investigation, and treatment with pituitary derived gonadotrophins and growth hormone. Molecular biochemistry of the CNS investigation revealed that a host encoded protein, the prion protein (PrP), accumulates proportionally to the infectious titer: this abnormality is the only detectable hallmark in TSE. Infectious fractions contain no detectable specific nucleic acid, and are mainly constituted of PrP under an isoform which resists to proteinase K digestion (PrP-res). The PrP gene (PRNP) is located on chromosome 20 in humans. Several mutations of this gene have been described in all inherited TSE (CJD, GSS, and IFF). No treatment is available today. Agents inducing TSE (TSA) are not known: several authors claim that TSA are only constituted of PrP-res; others support the hypothesis of a conventional agent with a specific genetic information.

Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.

PubMed

Hu, Minlu; Patel, Sravan Kumar; Zhou, Tian; Rohan, Lisa C

2015-12-10

Efflux and uptake transporters of drugs are key regulators of the pharmacokinetics of many antiretroviral drugs. A growing body of literature has revealed the expression and functionality of multiple transporters in female genital tract (FGT), colorectal tissue, and immune cells. Drug transporters could play a significant role in the efficacy of preventative strategies for HIV-1 acquisition. Pre-exposure prophylaxis (PrEP) is a promising strategy, which utilizes topically (vaginally or rectally), orally or other systemically administered antiretroviral drugs to prevent the sexual transmission of HIV to receptive partners. The drug concentration in the receptive mucosal tissues and target immune cells for HIV is critical for PrEP effectiveness. Hence, there is an emerging interest in utilizing transporter information to explain tissue disposition patterns of PrEP drugs, to interpret inter-individual variability in PrEP drug pharmacokinetics and effectiveness, and to improve tissue drug exposure through modulation of the cervicovaginal, colorectal, or immune cell transporters. In this review, the existing literature on transporter expression, functionality and regulation in the transmission-related tissues and cells is summarized. In addition, the relevance of transporter function for drug delivery and strategies that could exploit transporters for increased drug concentration at target locales is discussed. The overall goal is to facilitate an understanding of drug transporters for PrEP optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

The Impact of Cognitive Impairment on Efficacy of Pulmonary Rehabilitation in Patients With COPD.

PubMed

Cleutjens, Fiona A H M; Spruit, Martijn A; Ponds, Rudolf W H M; Vanfleteren, Lowie E G W; Franssen, Frits M E; Dijkstra, Jeanette B; Gijsen, Candy; Wouters, Emiel F M; Janssen, Daisy J A

2017-05-01

To compare changes in pulmonary rehabilitation (PR) dropout and outcomes between chronic obstructive pulmonary disease (COPD) patients with and without cognitive impairment. A cross-sectional observational study. Patients with COPD were recruited from a PR centre in the Netherlands. The study population consisted of 157 patients with clinically stable COPD who were referred for and completed PR. A comprehensive neuropsychological examination before start of PR was administered. Changes from baseline to PR completion in functional exercise capacity [6-minute walk test (6MWT)], disease-specific health status [COPD Assessment Test (CAT) and St George's Respiratory Questionnaire-COPD specific (SGRQ-C)], psychological well-being [Hospital Anxiety and Depression Scale (HADS)], COPD-related knowledge, and their need for information [Lung Information Needs Questionnaire (LINQ)] were compared between patients with and without cognitive impairment using independent samples t tests or Mann-Whitney U tests. Out of 157 patients with COPD [mean age 62.9 (9.4) years, forced expiratory volume in the first second 54.6% (22.9%) predicted], 24 patients (15.3%) did not complete PR. The dropout rate was worse in patients with cognitive impairment compared to those without cognitive impairment (23.3% and 10.3%, P = .03). Mean changes in PR outcomes after PR did not differ between completers with and without cognitive impairment. The proportion of patients with a clinically relevant improvement in 6MWT, CAT, SGRQ-C, HADS, and LINQ scores was comparable for patients with and without cognitive impairment. PR is an effective treatment for patients with COPD and cognitive impairment. Yet patients with cognitive impairment are at increased risk for not completing the PR program. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Novel nuclear magnetic resonance techniques for studying biological molecules

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

Laws, David Douglas

2000-06-01

Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. Inmore » this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (Φ/Ψ) dihedral angles by comparing experimentally determined 13C a, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.« less

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

Seong, Yeon-Jae; Hafis Clinic, Seoul; Sung, Pil Soo

Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced themore » production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.« less

Pre-Exposure Prophylaxis YouTube Videos: Content Evaluation

PubMed Central

Basch, Corey; Basch, Charles; Kernan, William

2018-01-01

Background Antiretroviral (ARV) medicines reduce the risk of transmitting the HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in combination with safer sex practices for HIV-negative individuals at a high risk for infection, but are underused in HIV prevention. Previous literature suggests that YouTube is extensively used to share health information. While pre-exposure prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is limited understanding of YouTube videos as a source of information on PrEP. Objective The objective of this study was to describe the sources, characteristics, and content of the most widely viewed PrEP YouTube videos published up to October 1, 2016. Methods The keywords “pre-exposure prophylaxis” and “Truvada” were used to find 217 videos with a view count >100. Videos were coded for source, view count, length, number of comments, and selected aspects of content. Videos were also assessed for the most likely target audience. Results The total cumulative number of views was >2.3 million, however, a single Centers for Disease Control and Prevention video accounted for >1.2 million of the total cumulative views. A great majority (181/217, 83.4%) of the videos promoted the use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas less than one third addressed the costs, side effects, and safety aspects relating to PrEP. Medical and academic institutions were the sources of the largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%), community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%). Videos uploaded by the media sources were more likely to discuss the cost of PrEP (P<.001), whereas the use of PrEP was less likely to be promoted in videos uploaded by individual consumers (P=.002) and more likely to be promoted in videos originated by CBOs (P=.009). The most common target audience for the videos was gay and bisexual men. Conclusions YouTube videos can be used to share reliable PrEP information with individuals. Further research is needed to identify the best practices for using this medium to promote and increase PrEP uptake. PMID:29467119

Dental caries and periodontal disease in Brazilian children and adolescents with cerebral palsy.

PubMed

Cardoso, Andreia M R; Gomes, Lays N; Silva, Clara Regina D; Soares, Renata de S C; Abreu, Mauro Henrique N G de; Padilha, Wilton W N; Cavalcanti, Alessandro L

2014-12-29

The aim of the present study was determine the prevalence and factors associated with dental caries and periodontal disease in Brazilian children and adolescents with cerebral palsy (CP). This is a cross-sectional study conducted with 80 patients ranging in age from 2 to 18 years old. Oral exams were conducted by an examiner with records of DMFT, dmft, Gingival Bleeding Index (GBI) and Community Periodontal Index (CPI). The statistical analysis used Poisson Regression with robust variance estimation (α = 0.05). The prevalence of dental caries was 59.3%, with DMFT and mean dmft of 1.71 ± 2.42 and 2.22 ± 3.23, respectively. The mean GBI was 22.44%, and in the CPI, the prevalence of gingival bleeding, calculus, shallow and deep pockets were 94.73%, 79.62%, 12.90% and 3.22%, respectively. The caregiver's educational level of less than eight years were associated with the dental caries experience (PR = 1.439; 95%CI = 1.09-1.89). The periodontal alterations were associated with female sex (PR = 0.82; 95%CI = 0.69-0.97), caregiver's educational level of less than eight years (PR = 1.15; 95%CI = 1.03-1.29), poor oral perception (PR = 0.89; 95%CI = 0.80-0.98), serious communication problem (PR = 0.87; 95%CI = 0.76-0.99) and athetoid type of CP (PR = 0.85; 95%CI = 0.75-0.97). The patients with CP presented high dental caries experience and periodontal alterations, which were associated with their demographic, socioeconomic, oral health perception and systemic information.

Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support.

PubMed

Calabrese, Sarah K; Underhill, Kristen; Earnshaw, Valerie A; Hansen, Nathan B; Kershaw, Trace S; Magnus, Manya; Krakower, Douglas S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F

2016-07-01

Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting ("beneficiary") and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts.

Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support

PubMed Central

Calabrese, Sarah K.; Underhill, Kristen; Earnshaw, Valerie A.; Hansen, Nathan B.; Kershaw, Trace S.; Magnus, Manya; Krakower, Douglas S.; Mayer, Kenneth H.; Betancourt, Joseph R.; Dovidio, John F.

2016-01-01

Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting (“beneficiary”) and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts. PMID:26891840

Diagnostic value and clinical laboratory associations of antibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in a Caucasian cohort with systemic lupus erythematosus.

PubMed

Barkhudarova, Fidan; Dähnrich, Cornelia; Rosemann, Anke; Schneider, Udo; Stöcker, Winfried; Burmester, Gerd-Rüdiger; Egerer, Karl; Schlumberger, Wolfgang; Hiepe, Falk; Biesen, Robert

2011-02-10

In this study, we sought to determine the diagnostic value and clinical laboratory associations of autoantibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in systemic lupus erythematosus (SLE). Autoantibodies against recombinant ribosomal P proteins (aRibPR0, aRibPR1 and aRibPR2) and antibodies against native ribosomal P heterocomplex (aRibPNH) were determined in sera from patients with SLE (n = 163), systemic sclerosis (n = 66), Sjögren's syndrome (n = 54), rheumatoid arthritis (n = 90) and healthy donors (n = 100) using enzyme-linked immunosorbent assay. Test results were correlated to medical records, including the American College of Rheumatology criteria, the Systemic Lupus Erythematosus Disease Activity Index 2000, laboratory data and medications of all SLE patients. Sensitivities of 22.0% for aRibPR0, 14.9% for aRibPR2, 14.3% for aRibPNH and 10.7% for aRibPR1 were obtained at a specificity of 99%. The assay for aRibPR0 detection demonstrated the best performance in receiver-operating characteristics analysis, with aRibPR0 detectable in 10% of anti-Smith antibody and anti-double-stranded DNA-negative sera at a specificity of 100%. ARibPR0 positivity was associated with lymphocytopenia. ARibPR1+ patients had significantly higher γ-glutamyl transpeptidase (GGT) levels than their aRibPR1- counterparts. No specific damage occurred in aRibP+ lupus patients compared with a group of age-, sex- and nephritis-matched aRibP- lupus patients within 3 years. The determination of antibodies against ribosomal P proteins improves the diagnosis of SLE and should therefore be implemented in upcoming criteria for the diagnosis or classification of SLE. High titers of aRibPR0 can be associated with lymphocytopenia, and high titers of aRibPR1 can be associated with elevated GGT levels. So far, there is no evidence for a prognostic value of aRibPs for damage.

Pattern recognition and expert image analysis systems in biomedical image processing (Invited Paper)

NASA Astrophysics Data System (ADS)

Oosterlinck, A.; Suetens, P.; Wu, Q.; Baird, M.; F. M., C.

1987-09-01

This paper gives an overview of pattern recoanition techniques (P.R.) used in biomedical image processing and problems related to the different P.R. solutions. Also the use of knowledge based systems to overcome P.R. difficulties, is described. This is illustrated by a common example ofabiomedical image processing application.

Pathogenesis of bovine spongiform encephalopathy in sheep.

PubMed

van Keulen, L J M; Vromans, M E W; Dolstra, C H; Bossers, A; van Zijderveld, F G

2008-01-01

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrP(Sc) accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrP(Sc) was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7-L1. At subsequent time points, PrP(Sc) was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrP(Sc) involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord.

Pathogenesis of bovine spongiform encephalopathy in sheep

PubMed Central

Vromans, M. E. W.; Dolstra, C. H.; Bossers, A.; van Zijderveld, F. G.

2007-01-01

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was detected after 6 months in the tonsil and the ileal Peyer’s patches. At 9 months postinfection, PrPSc accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrPSc accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrPSc was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7–L1. At subsequent time points, PrPSc was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrPSc involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord. PMID:18092124

Study of conduction behavior in Pr0.67Sr0.03Ag0.30MnO3

NASA Astrophysics Data System (ADS)

Bhat, Masroor Ahmad; Modi, Anchit; Pandey, Devendra K.; Gaur, N. K.

2018-05-01

In this paper, we report the conduction mechanism in Pr0.67Sr0.03Ag0.30MnO3 system synthesized via conventional solid state reaction route. The structural information was carried by X - Ray diffraction using Rietveld refinement which confirms the secondary phase of the sample. The SEM image shows the formation of double phase composite because of limited reaction of silver with parent compound. The resistivity behavior indicates the semiconducting behavior. The electronic nature can be estimated by means of variable range hopping (VRH) and small polaron hopping (SPH) model showing that the enhancement of double exchange interaction suppress the band gap and boost the carrier delocalization of charge carriers.

Thermodynamic database for the Co-Pr system.

PubMed

Zhou, S H; Kramer, M J; Meng, F Q; McCallum, R W; Ott, R T

2016-03-01

In this article, we describe data on (1) compositions for both as-cast and heat treated specimens were summarized in Table 1; (2) the determined enthalpy of mixing of liquid phase is listed in Table 2; (3) thermodynamic database of the Co-Pr system in TDB format for the research articled entitle Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W.

Thermodynamic database for the Co-Pr system

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

Zhou, S. H.; Kramer, M. J.; Meng, F. Q.

2016-01-21

In this article, we describe data on (1) compositions for both as-cast and heat treated specimens were summarized in Table 1; (2) the determined enthalpy of mixing of liquid phase is listed in Table 2; (3) thermodynamic database of the Co-Pr system in TDB format for the research articled entitle Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W.

Thermodynamic database for the Co-Pr system

DOE PAGES

Zhou, S. H.; Kramer, M. J.; Meng, F. Q.; ...

2016-03-01

In this article, we describe data on (1) compositions for both as-cast and heat treated specimens were summarized in Table 1; (2) the determined enthalpy of mixing of liquid phase is listed in Table 2; (3) thermodynamic database of the Co-Pr system in TDB format for the research articled entitled ''Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W.''

From PACS to Web-based ePR system with image distribution for enterprise-level filmless healthcare delivery.

PubMed

Huang, H K

2011-07-01

The concept of PACS (picture archiving and communication system) was initiated in 1982 during the SPIE medical imaging conference in New Port Beach, CA. Since then PACS has been matured to become an everyday clinical tool for image archiving, communication, display, and review. This paper follows the continuous development of PACS technology including Web-based PACS, PACS and ePR (electronic patient record), enterprise PACS to ePR with image distribution (ID). The concept of large-scale Web-based enterprise PACS and ePR with image distribution is presented along with its implementation, clinical deployment, and operation. The Hong Kong Hospital Authority's (HKHA) integration of its home-grown clinical management system (CMS) with PACS and ePR with image distribution is used as a case study. The current concept and design criteria of the HKHA enterprise integration of the CMS, PACS, and ePR-ID for filmless healthcare delivery are discussed, followed by its work-in-progress and current status.

Subepidermal moisture surrounding pressure ulcers in persons with a spinal cord injury: A pilot study

PubMed Central

Harrow, Jeffrey John; Mayrovitz, Harvey N.

2014-01-01

Objective Characterization of a non-invasive method of quantifying subepidermal moisture (SEM) surrounding stages III and IV pressure ulcers (PrUs) in spinal cord injury (SCI). Design Prospective, single-visit, single-rater, observational study, using repeated-measures analysis. Method Setting-inpatient units of one VA SCI Center. Participants Convenience sample of 16 subjects with SCI with stage III or IV PrUs over sacrum or ischium. Interventions Measurement with the MoistureMeter-D, a hand-held device using 300 MHz electromagnetic waves. Outcome measures Dielectric constant, a dimensionless number which increases with the moisture content. Each subject had a PrU site and a control site. Measurements were made at each site, on intact skin, at four points spaced angularly around the site, in triplicate. Results (1) Short-term, single-rater relative error was 2.5%. (2) Order effect: first readings were higher than second readings in 55 of 64 measurement sets. Order effect was significant for control sites (P < 0.0001) but not for PrU sites. (3) Angular effect: SEM varied by angle at the PrU sites (P < 0.01); 12 o'clock position the highest and 6 o'clock the lowest. (4) Ability to differentiate PrUs from intact skin: SEM at PrU sites was greater by 9.0% than control sites (P < 0.05). (5) Site effect: SEM was higher at sacral locations than ischial at control sites by 20% (P < 0.005). Conclusions SEM differentiates PrUs from intact skin. Future study designs must take into account order, angular, and site effects on this measure. This information will inform designers of future studies of SEM in healing of PrUs. PMID:25398030

A dynamical systems model of progesterone receptor interactions with inflammation in human parturition.

PubMed

Brubaker, Douglas; Barbaro, Alethea; R Chance, Mark; Mesiano, Sam

2016-08-19

Progesterone promotes uterine relaxation and is essential for the maintenance of pregnancy. Withdrawal of progesterone activity and increased inflammation within the uterine tissues are key triggers for parturition. Progesterone actions in myometrial cells are mediated by two progesterone receptor (PR) isoforms, PR-A and PR-B, that function as ligand-activated transcription factors. PR-B mediates relaxatory actions of progesterone, in part, by decreasing myometrial cell responsiveness to pro-inflammatory stimuli. These same pro-inflammatory stimuli promote the expression of PR-A which inhibits the anti-inflammatory activity of PR-B. Competitive interaction between the progesterone receptors then augments myometrial responsiveness to pro-inflammatory stimuli. The interaction between PR-B transcriptional activity and inflammation in the pregnancy myometrium is examined using a dynamical systems model in which quiescence and labor are represented as phase-space equilibrium points. Our model shows that PR-B transcriptional activity and the inflammatory load determine the stability of the quiescent and laboring phenotypes. The model is tested using published transcriptome datasets describing the mRNA abundances in the myometrium before and after the onset of labor at term. Surrogate transcripts were selected to reflect PR-B transcriptional activity and inflammation status. The model coupling PR-B activity and inflammation predicts contractile status (i.e., laboring or quiescent) with high precision and recall and outperforms uncoupled single and two-gene classifiers. Linear stability analysis shows that phase space bifurcations exist in our model that may reflect the phenotypic states of the pregnancy uterus. The model describes a possible tipping point for the transition of the quiescent to the contractile laboring phenotype. Our model describes the functional interaction between the PR-A:PR-B hypothesis and tissue level inflammation in the pregnancy uterus and is a first step in more sophisticated dynamical systems modeling of human partition. The model explains observed biochemical dynamics and as such will be useful for the development of a range of systems-based models using emerging data to predict preterm birth and identify strategies for its prevention.

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

PubMed Central

Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

2017-01-01

Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

Effect of Pr Valence State on Interfacial Structure and Electrical Properties of Pr Oxide/PrON/Ge Gate Stack Structure

NASA Astrophysics Data System (ADS)

Kato, Kimihiko; Sakashita, Mitsuo; Takeuchi, Wakana; Kondo, Hiroki; Nakatsuka, Osamu; Zaima, Shigeaki

2011-04-01

In this study, we investigated the valence state and chemical bonding state of Pr in a Pr oxide/PrON/Ge structure. We clarified the relationship between the valence state of Pr and the Pr oxide/Ge interfacial reaction using Pr oxide/Ge and Pr oxide/PrON/Ge samples. We found the formation of three Pr oxide phases in Pr oxide films; hexagonal Pr2O3 (h-Pr2O3) (Pr3+), cubic Pr2O3 (c-Pr2O3) (Pr3+), and c-PrO2 (Pr4+). We also investigated the effect of a nitride interlayer on the interfacial reaction in Pr oxide/Ge gate stacks. In a sample with a nitride interlayer (Pr oxide/PrON/Ge), metallic Pr-Pr bonds are also formed in the c-Pr2O3 film. After annealing in H2 ambient, the diffusion of Ge into Pr oxide is not observed in this sample. Pr-Pr bonds probably prevent the interfacial reaction and Ge oxide formation, considering that the oxygen chemical potential of this film is lower than that of a GeO2/Ge system. On the other hand, the rapid thermal oxidation (RTO) treatment terminates the O vacancies and defects in c-Pr2O3. As a result, c-PrO2 with tetravalent Pr is formed in the Pr oxide/PrON/Ge sample with RTO. In this sample, the leakage current density is effectively decreased in comparison with the sample without RTO. Hydrogen termination works effectively in Pr oxide/PrON/Ge samples with and without RTO, and we can achieve an interface state density of as low as 4 ×1011 eV-1·cm-2.

[Repeated pregnancy among adolescents and social vulnerability in Rio de Janeiro (RJ, Brazil): data analysis of Information System on Live Births].

PubMed

da Silva, Katia Silveira; Rozenberg, Riva; Bonan, Claudia; Chuva, Vânia Cristina Costa; da Costa, Simoni Furtado; Gomes, Maria Auxiliadora de Souza Mendes

2011-05-01

Repeated pregnancy (RP) among adolescents is seldom researched in Brazil, even tough the debate on the reproductive rights is important for this extract of population. A transversal study was developed with data from the Declaration of Live Births of adolescent mothers, living in Rio de Janeiro (RJ, Brazil), in 2005. The aim was to estimate the magnitude and features associated with RP. Prevalence ratios (PR) of RP, with 95% confidence interval (CI) for selected variables, were estimated through log-binomial multivariate regression. Among 12,168 adolescents, a RP prevalence of 29.1% was identified and the principal factors associated were: age 15-19 anos (PR=5.42; RI 95% 3.72-7.81); not doing prenatal consultation (RP=2.36; CI 95% 2.16-2.58); educational status<4 anos (PR=1.48; CI 95% 1.25-1.76); housewife job (PR=1.8; CI 95% 1.57-2.15) or other (PR=1.9; CI 95%; 1.73-2.10). Giving birth by cesarean section and low birth weight were negatively associated to repeated pregnancy with RP equal to 0,94 (CI 95%; 0,86-0,99) and 0.69 (CI 95%; 0.62-0.77). The adolescents with RP had worst socioeconomic and assistance indicators than those on their first pregnancy. Specific social policies for adolescent mothers, in vulnerable situation, will enable them to have better conditions to exercise their reproductive rights.

Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies.

PubMed

Hainfellner, J A; Budka, H

1999-11-01

There is increasing evidence indicating involvement of the peripheral nervous system (PNS) in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Immunocytochemically detectable deposits of TSE-specific abnormal prion protein (PrP(sc)) are considered as a surrogate marker for infectivity. We used anti-PrP immunocytochemistry to trace PrP(sc) deposition in spinal and enteric ganglia, and peripheral nerve in Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia. Discrete PrP(sc) deposits were detectable only in a few posterior root nerve fibers in an adaxonal location in one of nine CJD and the one GSS patients examined. Follicular dendritic cells of the gut and enteric nervous system were not labeled. Thus, PrP(sc) may spread to the PNS in different forms of human prion disease. In contrast to our observations in experimental scrapie (Groschup et al., Acta Neuropathol, this issue), the deposits were scant. Possible explanations for this discrepancy comprise strain difference, or centripetal (experimental scrapie) versus centrifugal (sporadic and genetic human prion diseases) spread of PrP(sc), resulting in different patterns and amounts of PrP(sc) accumulation in the PNS.

Hot spot of structural ambivalence in prion protein revealed by secondary structure principal component analysis.

PubMed

Yamamoto, Norifumi

2014-08-21

The conformational conversion of proteins into an aggregation-prone form is a common feature of various neurodegenerative disorders including Alzheimer's, Huntington's, Parkinson's, and prion diseases. In the early stage of prion diseases, secondary structure conversion in prion protein (PrP) causing β-sheet expansion facilitates the formation of a pathogenic isoform with a high content of β-sheets and strong aggregation tendency to form amyloid fibrils. Herein, we propose a straightforward method to extract essential information regarding the secondary structure conversion of proteins from molecular simulations, named secondary structure principal component analysis (SSPCA). The definite existence of a PrP isoform with an increased β-sheet structure was confirmed in a free-energy landscape constructed by mapping protein structural data into a reduced space according to the principal components determined by the SSPCA. We suggest a "spot" of structural ambivalence in PrP-the C-terminal part of helix 2-that lacks a strong intrinsic secondary structure, thus promoting a partial α-helix-to-β-sheet conversion. This result is important to understand how the pathogenic conformational conversion of PrP is initiated in prion diseases. The SSPCA has great potential to solve various challenges in studying highly flexible molecular systems, such as intrinsically disordered proteins, structurally ambivalent peptides, and chameleon sequences.

Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

PubMed

Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

2014-07-01

The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells.

PubMed

Dron, Michel; Dandoy-Dron, Françoise; Farooq Salamat, Muhammad Khalid; Laude, Hubert

2009-08-01

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrP(C)) and abnormal (PrP(Sc)) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrP(C), leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP(26K), accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP(26K) species converts into the highly proteinase K-resistant PrP(Sc). In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrP(Sc) that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrP(C) from the natural promoter, proteasomal impairment may affect both the process of PrP(C) biosynthesis and the subcellular sites of PrP(Sc) accumulation, despite the fact that these two effects could essentially be disconnected.

Solid state nuclear magnetic resonance studies of prion peptides and proteins

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

Heller, Jonathan

1997-08-01

High-resolution structural studies using x-ray diffraction and solution nuclear magnetic resonance (NMR) are not feasible for proteins of low volubility and high tendency to aggregate. Solid state NMR (SSNMR) is in principle capable of providing structural information in such systems, however to do this efficiently and accurately, further SSNMR tools must be developed This dissertation describes the development of three new methods and their application to a biological system of interest, the priori protein (PrP).

Pre-Exposure Prophylaxis YouTube Videos: Content Evaluation.

PubMed

Kecojevic, Aleksandar; Basch, Corey; Basch, Charles; Kernan, William

2018-02-16

Antiretroviral (ARV) medicines reduce the risk of transmitting the HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in combination with safer sex practices for HIV-negative individuals at a high risk for infection, but are underused in HIV prevention. Previous literature suggests that YouTube is extensively used to share health information. While pre-exposure prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is limited understanding of YouTube videos as a source of information on PrEP. The objective of this study was to describe the sources, characteristics, and content of the most widely viewed PrEP YouTube videos published up to October 1, 2016. The keywords "pre-exposure prophylaxis" and "Truvada" were used to find 217 videos with a view count >100. Videos were coded for source, view count, length, number of comments, and selected aspects of content. Videos were also assessed for the most likely target audience. The total cumulative number of views was >2.3 million, however, a single Centers for Disease Control and Prevention video accounted for >1.2 million of the total cumulative views. A great majority (181/217, 83.4%) of the videos promoted the use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas less than one third addressed the costs, side effects, and safety aspects relating to PrEP. Medical and academic institutions were the sources of the largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%), community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%). Videos uploaded by the media sources were more likely to discuss the cost of PrEP (P<.001), whereas the use of PrEP was less likely to be promoted in videos uploaded by individual consumers (P=.002) and more likely to be promoted in videos originated by CBOs (P=.009). The most common target audience for the videos was gay and bisexual men. YouTube videos can be used to share reliable PrEP information with individuals. Further research is needed to identify the best practices for using this medium to promote and increase PrEP uptake. ©Aleksandar Kecojevic, Corey Basch, Charles Basch, William Kernan. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 16.02.2018.

Underlying Chronic Disease, Medication Use, History of Running Injuries and Being a More Experienced Runner Are Independent Factors Associated With Exercise-Associated Muscle Cramping: A Cross-Sectional Study in 15778 Distance Runners.

PubMed

Schwellnus, Martin P; Swanevelder, Sonja; Jordaan, Esme; Derman, Wayne; Van Rensburg, Dina C Janse

2018-05-01

Exercise-associated muscle cramping (EAMC) is a significant medical complication in distance runners, yet factors associated with EAMC are poorly documented. To document risk factors associated with EAMC in runners. Cross-sectional study. Two ocean races (21.1 km, and 56 km). Fifteen thousand seven hundred seventy-eight race entrants. Participants completed a prerace medical history screening tool including: training, cardiovascular disease (CVD), risk factors for, and symptoms of CVD, history of diseases affecting major organ systems, cancer, allergies, medication use, and running injury. Runners were grouped as having a history of EAMC (hEAMC group = 2997) and a control group (Control = 12 781). Independent factors associated with a higher prevalence ratio (PR) of hEAMC were any risk factor for CVD (PR = 1.16; P = 0.0002), symptoms of CVD (PR = 2.38; P < 0.0001), respiratory disease (PR = 1.33; P < 0.0001), gastrointestinal disease (PR = 1.86; P < 0.0001), nervous system or psychiatric disease (PR = 1.51; P < 0.0001), kidney or bladder disease, (PR = 1.60; P < 0.0001), haematological or immune disease (PR = 1.54; P = 0.0048), cancer (PR = 1.34; P = 0.0031), allergies (PR = 1.37; P < 0.0001), regular medication use (PR = 1.80; P < 0.0001), statin use (PR = 1.26; P = 0.0127), medication use during racing (PR = 1.88; P < 0.0001), running injury (PR = 1.66; P < 0.0001), muscle injury (PR = 1.82; P < 0.0001), tendon injury (PR = 1.62; P < 0.0001), and runners in the experienced category (PR = 1.22; P < 0.0001). Novel risk factors associated with EAMC in distance runners were underlying chronic disease, medication use, a history of running injuries, and experienced runners. These factors must be identified as possible associations, and therefore be considered in the diagnosis and treatment of EAMC.

Dental Caries and Periodontal Disease in Brazilian Children and Adolescents with Cerebral Palsy

PubMed Central

Cardoso, Andreia M. R.; Gomes, Lays N.; Silva, Clara Regina D.; de S. C. Soares, Renata; de Abreu, Mauro Henrique N. G.; Padilha, Wilton W. N.; Cavalcanti, Alessandro L.

2014-01-01

The aim of the present study was determine the prevalence and factors associated with dental caries and periodontal disease in Brazilian children and adolescents with cerebral palsy (CP). This is a cross-sectional study conducted with 80 patients ranging in age from 2 to 18 years old. Oral exams were conducted by an examiner with records of DMFT, dmft, Gingival Bleeding Index (GBI) and Community Periodontal Index (CPI). The statistical analysis used Poisson Regression with robust variance estimation (α = 0.05). The prevalence of dental caries was 59.3%, with DMFT and mean dmft of 1.71 ± 2.42 and 2.22 ± 3.23, respectively. The mean GBI was 22.44%, and in the CPI, the prevalence of gingival bleeding, calculus, shallow and deep pockets were 94.73%, 79.62%, 12.90% and 3.22%, respectively. The caregiver’s educational level of less than eight years were associated with the dental caries experience (PR = 1.439; 95%CI = 1.09–1.89). The periodontal alterations were associated with female sex (PR = 0.82; 95%CI = 0.69–0.97), caregiver’s educational level of less than eight years (PR = 1.15; 95%CI = 1.03–1.29), poor oral perception (PR = 0.89; 95%CI = 0.80–0.98), serious communication problem (PR = 0.87; 95%CI = 0.76–0.99) and athetoid type of CP (PR = 0.85; 95%CI = 0.75–0.97). The patients with CP presented high dental caries experience and periodontal alterations, which were associated with their demographic, socioeconomic, oral health perception and systemic information. PMID:25551517

A framework of quality improvement interventions to implement evidence-based practices for pressure ulcer prevention.

PubMed

Padula, William V; Mishra, Manish K; Makic, Mary Beth F; Valuck, Robert J

2014-06-01

To enhance the learner's competence with knowledge about a framework of quality improvement (QI) interventions to implement evidence-based practices for pressure ulcer (PrU) prevention. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Summarize the process of creating and initiating the best-practice framework of QI for PrU prevention.2. Identify the domains and QI interventions for the best-practice framework of QI for PrU prevention. Pressure ulcer (PrU) prevention is a priority issue in US hospitals. The National Pressure Ulcer Advisory Panel endorses an evidence-based practice (EBP) protocol to help prevent PrUs. Effective implementation of EBPs requires systematic change of existing care units. Quality improvement interventions offer a mechanism of change to existing structures in order to effectively implement EBPs for PrU prevention. The best-practice framework developed by Nelson et al is a useful model of quality improvement interventions that targets process improvement in 4 domains: leadership, staff, information and information technology, and performance and improvement. At 2 academic medical centers, the best-practice framework was shown to physicians, nurses, and health services researchers. Their insight was used to modify the best-practice framework as a reference tool for quality improvement interventions in PrU prevention. The revised framework includes 25 elements across 4 domains. Many of these elements support EBPs for PrU prevention, such as updates in PrU staging and risk assessment. The best-practice framework offers a reference point to initiating a bundle of quality improvement interventions in support of EBPs. Hospitals and clinicians tasked with quality improvement efforts can use this framework to problem-solve PrU prevention and other critical issues.

Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches

PubMed Central

Hyeon, Jae Wook; Choi, Jiwon; Kim, Su Yeon; Govindaraj, Rajiv Gandhi; Jam Hwang, Kyu; Lee, Yeong Seon; An, Seong Soo A.; Lee, Myung Koo; Joung, Jong Young; No, Kyoung Tai; Lee, Jeongmin

2015-01-01

Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds. PMID:26449325

Research on control strategy based on fuzzy PR for grid-connected inverter

NASA Astrophysics Data System (ADS)

Zhang, Qian; Guan, Weiguo; Miao, Wen

2018-04-01

In the traditional PI controller, there is static error in tracking ac signals. To solve the problem, the control strategy of a fuzzy PR and the grid voltage feed-forward is proposed. The fuzzy PR controller is to eliminate the static error of the system. It also adjusts parameters of PR controller in real time, which avoids the defect of fixed parameter fixed. The grid voltage feed-forward control can ensure the quality of current and improve the system's anti-interference ability when the grid voltage is distorted. Finally, the simulation results show that the system can output grid current with good quality and also has good dynamic and steady state performance.

Adaptive training of cortical feature maps for a robot sensorimotor controller.

PubMed

Adams, Samantha V; Wennekers, Thomas; Denham, Sue; Culverhouse, Phil F

2013-08-01

This work investigates self-organising cortical feature maps (SOFMs) based upon the Kohonen Self-Organising Map (SOM) but implemented with spiking neural networks. In future work, the feature maps are intended as the basis for a sensorimotor controller for an autonomous humanoid robot. Traditional SOM methods require some modifications to be useful for autonomous robotic applications. Ideally the map training process should be self-regulating and not require predefined training files or the usual SOM parameter reduction schedules. It would also be desirable if the organised map had some flexibility to accommodate new information whilst preserving previous learnt patterns. Here methods are described which have been used to develop a cortical motor map training system which goes some way towards addressing these issues. The work is presented under the general term 'Adaptive Plasticity' and the main contribution is the development of a 'plasticity resource' (PR) which is modelled as a global parameter which expresses the rate of map development and is related directly to learning on the afferent (input) connections. The PR is used to control map training in place of a traditional learning rate parameter. In conjunction with the PR, random generation of inputs from a set of exemplar patterns is used rather than predefined datasets and enables maps to be trained without deciding in advance how much data is required. An added benefit of the PR is that, unlike a traditional learning rate, it can increase as well as decrease in response to the demands of the input and so allows the map to accommodate new information when the inputs are changed during training. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-resolution structure of infectious prion protein: the final frontier

PubMed Central

Diaz-Espinoza, Rodrigo; Soto, Claudio

2014-01-01

Prions are the proteinaceous infectious agents responsible for the transmission of prion diseases. The main or sole component of prions is the misfolded prion protein (PrPSc), which is able to template the conversion of the host’s natively folded form of the protein (PrPC). The detailed mechanism of prion replication and the high-resolution structure of PrPSc are unknown. The currently available information on PrPSc structure comes mostly from low-resolution biophysical techniques, which have resulted in quite divergent models. Recent advances in the production of infectious prions, using very pure recombinant protein, offer new hope for PrPSc structural studies. This review highlights the importance of, challenges for and recent progress toward elucidating the elusive structure of PrPSc, arguably the major pending milestone to reach in understanding prions. PMID:22472622

Young Transgender Women's Attitudes Toward HIV Pre-exposure Prophylaxis.

PubMed

Wood, Sarah M; Lee, Susan; Barg, Frances K; Castillo, Marne; Dowshen, Nadia

2017-05-01

Our primary aim was to explore themes regarding attitudes toward HIV pre-exposure prophylaxis (PrEP) among young transgender women (YTW), in order to develop a theoretical model of PrEP uptake in this population disproportionally affected by HIV. Qualitative study nested within a mixed-method study characterizing barriers and facilitators to health services for YTW. Participants completed an in-depth interview exploring awareness of and attitudes toward PrEP. Key themes were identified using a grounded theory approach. Participants (n = 25) had a mean age of 21.2 years (standard deviation 2.2, range 17-24) and were predominately multiracial (36%) and of HIV-negative or unknown status (68%). Most participants (64%) reported prior knowledge of PrEP, and 28% reported current use or intent to use PrEP. Three major content themes that emerged were variability of PrEP awareness, barriers and facilitators to PrEP uptake, and emotional benefits of PrEP. Among participants without prior PrEP knowledge, participants reported frustration that PrEP information has not been widely disseminated to YTW, particularly by health care providers. Attitudes toward PrEP were overwhelmingly positive; however, concerns were raised regarding barriers including cost, stigma, and adherence challenges. Both HIV-positive and negative participants discussed emotional and relationship benefits of PrEP, which were felt to extend beyond HIV prevention alone. A high proportion of YTW in this study had prior knowledge of PrEP, and attitudes toward PrEP were positive among participants. Our findings suggest several domains to be further explored in PrEP implementation research, including methods of facilitating PrEP dissemination and emotional motivation for PrEP uptake. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

TRMM .25 deg x .25 deg Gridded Precipitation Text Product

NASA Technical Reports Server (NTRS)

Stocker, Erich; Kelley, Owen

2009-01-01

Since the launch of the Tropical Rainfall Measuring Mission (TRMM), the Precipitation Measurement Missions science team has endeavored to provide TRMM precipitation retrievals in a variety of formats that are more easily usable by the broad science community than the standard Hierarchical Data Format (HDF) in which TRMM data is produced and archived. At the request of users, the Precipitation Processing System (PPS) has developed a .25 x .25 gridded product in an easily used ASCII text format. The entire TRMM mission data has been made available in this format. The paper provides the details of this new precipitation product that is designated with the TRMM designator 3G68.25. The format is packaged into daily files. It provides hourly precipitation information from the TRMM microwave imager (TMI), precipitation radar (PR), and TMI/PR combined rain retrievals. A major advantage of this approach is the inclusion only of rain data, compression when a particular grid has no rain from the PR or combined, and its direct ASCII text format. For those interested only in rain retrievals and whether rain is convection or stratiform, these products provide a huge reduction in the data volume inherent in the standard TRMM products. This paper provides examples of the 3G68 data products and their uses. It also provides information about C tools that can be used to aggregate daily files into larger time samples. In addition, it describes the possibilities inherent in the spatial sampling which allows resampling into coarser spatial sampling. The paper concludes with information about downloading the gridded text data products.

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

PubMed

Yoong, Deborah; Naccarato, Mark; Sharma, Malika; Wilton, James; Senn, Heather; Tan, Darrell Hs

2016-07-01

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted. © The Author(s) 2015.

Economic evaluation of HIV pre-exposure prophylaxis among men-who-have-sex-with-men in England in 2016.

PubMed

Ong, Koh Jun; Desai, Sarika; Field, Nigel; Desai, Monica; Nardone, Anthony; van Hoek, Albert Jan; Gill, Owen Noel

2017-10-01

Clinical effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV acquisition in men who have sex with men (MSM) at high HIV risk is established. A static decision analytical model was constructed to inform policy prioritisation in England around cost-effectiveness and budgetary impact of a PrEP programme covering 5,000 MSM during an initial high-risk period. National genitourinary medicine clinic surveillance data informed key HIV risk assumptions. Pragmatic large-scale implementation scenarios were explored. At 86% effectiveness, PrEP given to 5,000 MSM at 3.3 per 100 person-years annual HIV incidence, assuming risk compensation (20% HIV incidence increase), averted 118 HIV infections over remaining lifetimes and was cost saving. Lower effectiveness (64%) gave an incremental cost-effectiveness ratio of + GBP 23,500 (EUR 32,000) per quality-adjusted life year (QALY) gained. Investment of GBP 26.9 million (EUR 36.6 million) in year-1 breaks even anywhere from year-23 (86% effectiveness) to year-33 (64% effectiveness). PrEP cost-effectiveness was highly sensitive to year-1 HIV incidence, PrEP adherence/effectiveness, and antiretroviral drug costs. There is much uncertainty around HIV incidence in those given PrEP and adherence/effectiveness, especially under programme scale-up. Substantially reduced PrEP drug costs are needed to give the necessary assurance of cost-effectiveness, and for an affordable public health programme of sufficient size.

The Biological Function of the Prion Protein: A Cell Surface Scaffold of Signaling Modules.

PubMed

Linden, Rafael

2017-01-01

The prion glycoprotein (PrP C ) is mostly located at the cell surface, tethered to the plasma membrane through a glycosyl-phosphatydil inositol (GPI) anchor. Misfolding of PrP C is associated with the transmissible spongiform encephalopathies (TSEs), whereas its normal conformer serves as a receptor for oligomers of the β-amyloid peptide, which play a major role in the pathogenesis of Alzheimer's Disease (AD). PrP C is highly expressed in both the nervous and immune systems, as well as in other organs, but its functions are controversial. Extensive experimental work disclosed multiple physiological roles of PrP C at the molecular, cellular and systemic levels, affecting the homeostasis of copper, neuroprotection, stem cell renewal and memory mechanisms, among others. Often each such process has been heralded as the bona fide function of PrP C , despite restricted attention paid to a selected phenotypic trait, associated with either modulation of gene expression or to the engagement of PrP C with a single ligand. In contrast, the GPI-anchored prion protein was shown to bind several extracellular and transmembrane ligands, which are required to endow that protein with the ability to play various roles in transmembrane signal transduction. In addition, differing sets of those ligands are available in cell type- and context-dependent scenarios. To account for such properties, we proposed that PrP C serves as a dynamic platform for the assembly of signaling modules at the cell surface, with widespread consequences for both physiology and behavior. The current review advances the hypothesis that the biological function of the prion protein is that of a cell surface scaffold protein, based on the striking similarities of its functional properties with those of scaffold proteins involved in the organization of intracellular signal transduction pathways. Those properties are: the ability to recruit spatially restricted sets of binding molecules involved in specific signaling; mediation of the crosstalk of signaling pathways; reciprocal allosteric regulation with binding partners; compartmentalized responses; dependence of signaling properties upon posttranslational modification; and stoichiometric requirements and/or oligomerization-dependent impact on signaling. The scaffold concept may contribute to novel approaches to the development of effective treatments to hitherto incurable neurodegenerative diseases, through informed modulation of prion protein-ligand interactions.

PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer

PubMed Central

Davenport, Kristen A.; Hoover, Clare E.; Bian, Jifeng; Telling, Glenn C.; Mathiason, Candace K.; Hoover, Edward A.

2017-01-01

The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs. PMID:28880938

A Comprehensive Program to Reduce Rates of Hospital-Acquired Pressure Ulcers in a System of Community Hospitals.

PubMed

Englebright, Jane; Westcott, Ruth; McManus, Kathryn; Kleja, Kacie; Helm, Colleen; Korwek, Kimberly M; Perlin, Jonathan B

2018-03-01

The prevention of hospital-acquired pressure ulcers (PrUs) has significant consequences for patient outcomes and the cost of care. Providers are challenged with evaluating available evidence and best practices, then implementing programs and motivating change in various facility environments. In a large system of community hospitals, the Reducing Hospital Acquired-PrUs Program was developed to provide a toolkit of best practices, timely and appropriate data for focusing efforts, and continuous implementation support. Baseline data on PrU rates helped focus efforts on the most vulnerable patients and care situations. Facilities were empowered to use and adapt available resources to meet local needs and to share best practices for implementation across the system. Outcomes were measured by the rate of hospital-acquired PrUs, as gathered from patient discharge records. The rate of hospital-acquired stage III and IV PrUs decreased 66.3% between 2011 and 2013. Of the 149 participating facilities, 40 (27%) had zero hospital-acquired stage III and IV PrUs and 77 (52%) had a reduction in their PrU rate. Rates of all PrUs documented as present on admission did not change during this period. A comparison of different strategies used by the most successful facilities illustrated the necessity of facility-level flexibility and recognition of local workflows and patient demographics. Driven by the combination of a repository of evidence-based tools and best practices, readily available data on PrU rates, and local flexibility with processes, the Reducing Hospital Acquired-PrUs Program represents the successful operationalization of improvement in a wide variety of facilities.

Benefits of pulmonary rehabilitation in idiopathic pulmonary fibrosis.

PubMed

Swigris, Jeffrey J; Fairclough, Diane L; Morrison, Marianne; Make, Barry; Kozora, Elizabeth; Brown, Kevin K; Wamboldt, Frederick S

2011-06-01

Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR's effects on certain important outcomes is lacking. We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. PR improves functional capacity and fatigue in patients with IPF. (Clinical Trials.gov registration NCT00692796.)

Awareness and Willingness to Use Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men and Transgender Women in Brazil.

PubMed

Hoagland, Brenda; De Boni, Raquel B; Moreira, Ronaldo I; Madruga, José Valdez; Kallas, Esper G; Goulart, Silvia Pereira; Cerqueira, Natalia; Torres, Thiago S; Luz, Paula M; Fernandes, Nilo Martinez; Liu, Albert Y; Grinsztejn, Beatriz; Veloso, Valdilea G

2017-05-01

Antiretroviral pre-exposure prophylaxis (PrEP) is recommended to prevent HIV infection among high-risk men who have sex with men (MSM) though not available in Brazil where the HIV epidemic persists unabated in this group. This cross-sectional study describes PrEP awareness and willingness and associated factors among MSM and transvestite/transgender women (trans women) pre-screened for the PrEP Brasil study. Awareness was reported by 61.3 % of the participants and was associated with age, education, site, study period and prior HIV testing. Most participants (82.1 %) were willing to use PrEP, which was associated with site, study period, number of male condomless anal sexual partners and anal sex with HIV positive/unknown partners. PrEP information is need among young and less educated individuals. Willingness to use PrEP was high and future studies should be conducted to confirm PrEP acceptability and the characteristics of the population who chose to adopt this intervention.

PrEP Uptake, Adherence, and Discontinuation among California YMSM Using Geosocial Networking Applications

PubMed Central

Holloway, Ian; Dougherty, Ryan; Gildner, Jennifer; Beougher, Sean C.; Pulsipher, Craig; Montoya, Jorge A.; Plant, Aaron; Leibowitz, Arleen

2016-01-01

We investigated PrEP uptake, adherence, and discontinuation among young app-using MSM in California (N=761). 9.7% of participants had ever used PrEP; 87% of those deemed good candidates for screening (indicated by a CDC risk index score ≥10) were not current or past users. PrEP use was associated with higher income (aOR:4.13; CI:1.87-9.12), receptive condomless anal sex(aOR:3.41; CI:1.71-6.78), HIV-positive sex partners (aOR:2.87; CI:1.53-5.38), popper use (aOR:3.47; CI:1.96-6.13), and recent STI diagnosis (aOR:2.90; CI:1.64-5.13). 41.5% of users wanted help remembering to take PrEP. The top reason for discontinuation was concern about long-term side effects (33.0%). YMSM app users are prime candidates for PrEP, despite low uptake. Apps may be useful tools for PrEP information dissemination, adherence monitoring, and support. PMID:27552158

Experimental oxygen potentials of U 1-yPr yO 2± x and thermodynamic assessment of the U-Pr-O system

DOE PAGES

McMurray, Jake W.; Silva, Chinthaka M.

2015-12-09

Thermogravimetric analysis (TGA) was used to determine the oxygen potentials of fluorite urania-praseodymia (U 1-yPr yO 2± x) solid solutions for y = 0.10 and 0.20 between 1000 and 1500 °C. A thermodynamic assessment of U-Pr-O system was performed using the CALPHAD (CALculation of PHAse Diagrams) method. Furthermore, the models well reproduce the TGA measurements and the computed phase relations are in good agreement with those proposed from an X-ray diffraction investigation.

The 7 × 1 Fermi Surface Reconstruction in a Two-dimensional f -electron Charge Density Wave System: PrTe 3

DOE PAGES

Lee, Eunsook; Kim, D. H.; Kim, Hyun Woo; ...

2016-07-25

The electronic structure of a charge density wave (CDW) system PrTe 3 and its modulated structure in the CDW phase have been investigated by employing ARPES, XAS, Pr 4 f RPES, and first-principles band structure calculation. Pr ions are found to be nearly trivalent, supporting the CDW instability in the metallic Te sheets through partial filling. Finite Pr 4 f spectral weight is observed near the Fermi level, suggesting the non-negligible Pr 4 f contribution to the CDW formation through the Pr 4 f -Te 5p hybridization. The two-fold symmetric features in the measured Fermi surface (FS) of PrTe 3more » are explained by the calculated FS for the assumed 7 × 1 CDW supercell formation in Te sheets. The shadow bands and the corresponding very weak FSs are observed, which originate from both the band folding due to the 3D interaction of Te sheets with neighboring Pr-Te layers and that due to the CDW-induced FS reconstruction. The straight vertical FSs are observed along k z, demonstrating the nearly 2D character for the near-EF states. The observed linear dichroism reveals the in-plane orbital character of the near-E F Te 5p states.« less

Sexual partnerships and considerations for HIV antiretroviral pre-exposure prophylaxis utilization among high-risk substance using men who have sex with men.

PubMed

Mimiaga, Matthew J; Closson, Elizabeth F; Kothary, Vishesh; Mitty, Jennifer A

2014-01-01

Men who have sex with men (MSM) remain at great risk of HIV in the United States, representing 65 % of incident HIV infections. One factor contributing to the high rate of HIV infection among MSM is use of "recreational" drugs that are highly associated with unprotected anal sex. Pre-exposure chemoprophylaxis (PrEP) is a novel biomedical HIV prevention strategy that has the potential to reduce HIV transmission in MSM. Main and casual sex partners play a role in HIV prevention efforts for MSM. The study aimed to qualitatively explore the perceived influences of sexual relationships on promoting and inhibiting PrEP use among high-risk MSM who report regular drug use. Semi-structured qualitative interviews were conducted with 40 participants recruited in Boston, Massachusetts. Data were analyzed using descriptive qualitative analysis. Casual partners presented a distinct set of concerns from primary partnerships. MSM generally viewed main partners as a potential source of support for taking PrEP. Given their informal and often temporary nature, PrEP disclosure to casual partners was considered unnecessary. HIV-related stigma and substance use were also perceived as barriers to discussing PrEP use with casual partners. MSM articulated a high degree of personal agency regarding their ability to take PrEP. Findings suggest that behavioral interventions to improve PrEP utilization and adherence for high-risk MSM should be tailored to sex partner type and the parameters established between sex partners. Approaches to PrEP disclosure and partner engagement should be informed by the relative benefits and limitations characterized by these different types of relationships.

Reduced attentional blink for gambling-related stimuli in problem gamblers.

PubMed

Brevers, Damien; Cleeremans, Axel; Tibboel, Helen; Bechara, Antoine; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

2011-09-01

Although there is considerable information concerning the attentional biases in psychoactive substance use and misuse, much less is known about the contribution of attentional processing in problem gambling. The aim of this study was to examine whether problem gamblers (PrG) exhibit attentional bias at the level of the encoding processing stage. Forty PrG and 35 controls participated in an attentional blink (AB) paradigm in which they were required to identify both gambling and neutral words that appeared in a rapid serial visual presentation. Explicit motivation (e.g., intrinsic/arousal, extrinsic, amotivation) toward the gambling cues was recorded. A diminished AB effect for gambling-related words compared to neutral targets was identified in PrG. In contrast, AB was similar when either gambling-related or neutral words were presented to controls. Furthermore, there was a significant positive correlation between the reduced AB for gambling-related words and the sub-score of intrinsic/arousal motivation to gamble in PrG. Such findings suggest that the PrG group exhibits an enhanced ability to process gambling-related information, which is associated with their desire to gamble for arousal reasons. Theoretical and clinical implications of these results are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials.

PubMed

Jensen, Maj-Britt; Nielsen, Torsten O; Knoop, Ann S; Laenkholm, Anne-Vibeke; Balslev, Eva; Ejlertsen, Bent

2018-01-01

Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characteristics and subtypes as assigned by immunohistochemistry panels. In November 1977 through January 1983, 2862 patients with tumors larger than 5 cm or positive axillary nodes were included in the DBCG 77 trials. Archival tumor tissue from patients randomly assigned to no systemic treatment was analyzed for ER, PR, Ki67, EGFR and HER2. Intrinsic subtypes were defined as follows: Luminal A, ER or PR >0%, HER2-negative, PR >10% and Ki67 < 14%; Luminal B, ER or PR >0%, (PR ≤10% or HER2-positive or Ki67 ≥ 14%); HER2E, ER 0%, PR 0%, HER2 positive; Core basal, ER 0%, PR 0%, HER2 negative and EGFR positive. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics. In a multivariate model, mortality rate was significantly associated with age, tumor size, nodal status, invasion, histological type and grade, as well as subtype classification. With 35 years of follow-up, in this population of high-risk patients with no systemic therapy, no subgroup based on a composite prognostic score and/or molecular subtypes could be identified without excess mortality as compared to the background population.

Reactions and Receptivity to Framing HIV Prevention Message Concepts About Pre-Exposure Prophylaxis for Black and Latino Men Who Have Sex with Men in Three Urban US Cities.

PubMed

Mimiaga, Matthew J; Closson, Elizabeth F; Battle, Shanice; Herbst, Jeffrey H; Denson, Damian; Pitts, Nicole; Holman, Jeremy; Landers, Stewart; Mansergh, Gordon

2016-10-01

Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada ® ) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the PrEP efficacy data. Despite being concerned that other MSM would interpret the messages to mean that condom use was unnecessary while taking PrEP, participants themselves primarily understood PrEP as a supplement rather than a replacement for condoms. Based on their experience with taking antiretroviral medication, HIV-positive men considered condom use a more feasible form of HIV prevention than PrEP. Participants' responses suggest that more information about PrEP and the clinical trial would support the legitimacy of PrEP and the messages as a whole. These details may enhance believability in the concept of PrEP and reinforce confidence in the validity of the efficacy result.

Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling

PubMed Central

Singhal, Hari; Greene, Marianne E.; Zarnke, Allison L.; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G.; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B.; Nickisch, Klaus J.; Long, Henry W.; Becker, Lev; Brown, Myles; Greene, Geoffrey L.

2018-01-01

Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic. PMID:29435103

75 FR 10026 - Proposed Collection; Comment Request for Forms W-2, W-2c, W-2AS, W-2GU, W-2VI, W-3, W-3c, W-3cPR...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-04

... Wage and Tax Statements), W-3PR (Informe de Comprobantes de Retencion), W-3cPR (Transmission de Comprobantes de Retencion Corregidos), and W-3SS (transmittal of Wage and Tax Staements). OMB Number: 1545-0008... Actions: There are no changes being made to the form at this time. Type of Review: Extension of a...

Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics.

PubMed

Hu, J; Jiang, J; Wang, N

2018-02-01

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing 'Candidatus Liberibacter asiaticus' titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of 'Ca. L. asiaticus' titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.

INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Polar Mixing Optical Phonon Spectra in Wurtzite GaN Cylindrical Quantum Dots: Quantum Size and Dielectric Effects

NASA Astrophysics Data System (ADS)

Zhang, Li; Liao, Jian-Shang

2010-05-01

The interface-optical-propagating (IO-PR) mixing phonon modes of a quasi-zero-dimensional (QoD) wurtzite cylindrical quantum dot (QD) structure are derived and studied by employing the macroscopic dielectric continuum model. The analytical phonon states of IO-PR mixing modes are given. It is found that there are two types of IO-PR mixing phonon modes, i.e. ρ-IO/z-PR mixing modes and the z-IO/ρ-PR mixing modes existing in QoD wurtzite QDs. And each IO-PR mixing modes also have symmetrical and antisymmetrical forms. Via a standard procedure of field quantization, the Fröhlich Hamiltonians of electron-(IO-PR) mixing phonons interaction are obtained. Numerical calculations on a wurtzite GaN cylindrical QD are performed. The results reveal that both the radial-direction size and the axial-direction size as well as the dielectric matrix have great influence on the dispersive frequencies of the IO-PR mixing phonon modes. The limiting features of dispersive curves of these phonon modes are discussed in depth. The phonon modes “reducing" behavior of wurtzite quantum confined systems has been observed obviously in the structures. Moreover, the degenerating behaviors of the IO-PR mixing phonon modes in wurtzite QoD QDs to the IO modes and PR modes in wurtzite Q2D QW and Q1D QWR systems are analyzed deeply from both of the viewpoints of physics and mathematics.

Heterobimetallic transition metal/rare earth metal bifunctional catalysis: a Cu/Sm/Schiff base complex for syn-selective catalytic asymmetric nitro-Mannich reaction.

PubMed

Handa, Shinya; Gnanadesikan, Vijay; Matsunaga, Shigeki; Shibasaki, Masakatsu

2010-04-07

The full details of a catalytic asymmetric syn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes are described, demonstrating the effectiveness of the heterobimetallic transition metal/rare earth metal bifunctional catalysis. The first-generation system prepared from Cu(OAc)(2)/Sm(O-iPr)(3)/Schiff base 1a = 1:1:1 with an achiral phenol additive was partially successful for achieving the syn-selective catalytic asymmetric nitro-Mannich reaction. The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)(3), we reoptimized the catalyst preparation method, and a catalyst derived from Sm(5)O(O-iPr)(13) showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)(3). The optimal system with Sm(5)O(O-iPr)(13) was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti = >20:1-13:1. Catalytic asymmetric synthesis of nemonapride is also demonstrated using the catalyst derived from Sm(5)O(O-iPr)(13).

Primary care clinicians' experiences prescribing HIV pre-exposure prophylaxis at a specialized community health centre in Boston: lessons from early adopters.

PubMed

Krakower, Douglas S; Maloney, Kevin M; Grasso, Chris; Melbourne, Katherine; Mayer, Kenneth H

2016-01-01

An estimated 1.2 million Americans have indications for using antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at-risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Thirty-two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11-33). Most clinicians reported testing and risk-reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale-up of this efficacious intervention.

Assessing park-and-ride impacts.

DOT National Transportation Integrated Search

2010-06-01

Efficient transportation systems are vital to quality-of-life and mobility issues, and an effective park-and-ride (P&R) : network can help maximize system performance. Properly placed P&R facilities are expected to result in fewer calls : to increase...

A web-based e-learning application for wound diagnosis and treatment.

PubMed

Veredas, Francisco J; Ruiz-Bandera, Esperanza; Villa-Estrada, Francisca; Rufino-González, Juan F; Morente, Laura

2014-10-01

Pressure ulcers (PrU) are considered as one of the most challenging problems that Nursing professionals have to deal with in their daily practice. Nowadays, the education on PrUs is mainly based on traditional lecturing, seminars and face-to-face instruction, sometimes with the support of photographs of wounds being used as teaching material. This traditional educational methodology suffers from some important limitations, which could affect the efficacy of the learning process. This current study has been designed to introduce information and communication technologies (ICT) in the education on PrU for undergraduate students, with the main objective of evaluating the advantages an disadvantages of using ICT, by comparing the learning results obtained from using an e-learning tool with those from a traditional teaching methodology. In order to meet this major objective, a web-based learning system named ePULab has been designed and developed as an adaptive e-learning tool for the autonomous acquisition of knowledge on PrU evaluation. This innovative system has been validated by means of a randomized controlled trial that compares its learning efficacy with that from a control group receiving a traditional face-to-face instruction. Students using ePULab gave significantly better (p<0.01) learning acquisition scores (from pre-test mean 8.27 (SD 1.39) to post-test mean 15.83 (SD 2.52)) than those following traditional lecture-style classes (from pre-test mean 8.23 (SD 1.23) to post-test mean 11.6 (SD 2.52)). In this article, the ePULab software is described in detail and the results from that experimental educational validation study are also presented and analyzed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Obesity Prevalence by Occupation in Washington State, Behavioral Risk Factor Surveillance System

PubMed Central

Lu, Dayu; Fan, Z. Joyce

2014-01-01

Introduction Data that estimate the prevalence of and risk factors for worker obesity by occupation are generally unavailable and could inform the prioritization of workplace wellness programs. The aims of this study were to estimate the prevalence of obesity by occupation, examine the association of occupational physical activity and a range of health behaviors with obesity, and identify occupations in which workers are at high risk of obesity in Washington State. Methods We conducted descriptive and multivariable analyses among 37,626 employed Washington State respondents using the Behavioral Risk Factor Surveillance System in odd numbered years, from 2003 through 2009. We estimated prevalence and prevalence ratios (PRs) by occupational groups adjusting for demographics, occupational physical activity level, smoking, fruit and vegetable consumption, and leisure-time physical activity (LPTA). Results Overall obesity prevalence was 24.6% (95% confidence interval [CI], 24.0–25.1). Workers in protective services were 2.46 (95% CI, 1.72–3.50) times as likely to be obese as workers in health diagnosing occupations. Compared with their counterparts, workers who consumed adequate amounts of fruits and vegetables and had adequate LTPA were significantly less likely to be obese (PR = 0.91; 95% CI, 0.86–0.97 and PR = 0.63; 95% CI, 0.60–0.67, respectively). Workers with physically demanding occupational physical activity had a lower PR of obesity (PR = 0.83; 95% CI, 0.78–0.88) than those with nonphysically demanding occupational physical activity. Conclusion Obesity prevalence and health risk behaviors vary substantially by occupation. Employers, policy makers, and health promotion practitioners can use our results to target and prioritize workplace obesity prevention and health behavior promotion programs. PMID:24406093

Commercial-Off-the-Shelf (COTS), Volatile Organic Compounds (VOCs) and Hazardous Air Pollutants (HAPs)-Free, Non-Chromate Low Temperature Powder Coating (LTPC) System for United States Air Force use (PHASE II )

DTIC Science & Technology

2017-09-12

and Hazardous Air Pollutants (HAPs)-Free, non -chromate low temperature powder coating (LTPC) system for United States Air Force use PHASE II PR...required to support and successfully complete this effort. 1.1 Objective(s). The Contractor shall be required to demonstrate a non -chromate...5.0 General Information 5.1 Continuation of Mission-Essential Services During a Crisis. The Functional Commander (FC) or civilian equivalent has

Sexual Behavior, Risk Compensation, and HIV Prevention Strategies Among Participants in the San Francisco PrEP Demonstration Project: A Qualitative Analysis of Counseling Notes.

PubMed

Carlo Hojilla, J; Koester, Kimberly A; Cohen, Stephanie E; Buchbinder, Susan; Ladzekpo, Deawodi; Matheson, Tim; Liu, Albert Y

2016-07-01

Pre-exposure prophylaxis (PrEP) is a viable HIV prevention strategy but risk compensation could undermine potential benefits. There are limited data that examine this phenomenon outside of clinical trials. We conducted a qualitative analysis of counseling notes from the San Francisco site of the US PrEP demonstration project to assess how men who have sex with men used PrEP as a prevention strategy and its impact on their sexual practices. Four major themes emerged from our analysis of 130 distinct notes associated with 26 participants. Prevention strategy decision-making was dynamic, often influenced by the context and perceived risk of a sexual encounter. Counselors noted that participants used PrEP in conjunction with other health promotion strategies like condoms, asking about HIV status of their sex partners, and seroadaptation. With few exceptions, existing risk reduction strategies were not abandoned upon initiation of PrEP. Risk-taking behavior was 'seasonal' and fluctuations were influenced by various personal, psychosocial, and health-related factors. PrEP also helped relieve anxiety regarding sex and HIV, particularly among serodiscordant partners. Understanding sexual decision-making and how PrEP is incorporated into existing prevention strategies can help inform future PrEP implementation efforts.

Role of working memory and lexical knowledge in perceptual restoration of interrupted speech.

PubMed

Nagaraj, Naveen K; Magimairaj, Beula M

2017-12-01

The role of working memory (WM) capacity and lexical knowledge in perceptual restoration (PR) of missing speech was investigated using the interrupted speech perception paradigm. Speech identification ability, which indexed PR, was measured using low-context sentences periodically interrupted at 1.5 Hz. PR was measured for silent gated, low-frequency speech noise filled, and low-frequency fine-structure and envelope filled interrupted conditions. WM capacity was measured using verbal and visuospatial span tasks. Lexical knowledge was assessed using both receptive vocabulary and meaning from context tests. Results showed that PR was better for speech noise filled condition than other conditions tested. Both receptive vocabulary and verbal WM capacity explained unique variance in PR for the speech noise filled condition, but were unrelated to performance in the silent gated condition. It was only receptive vocabulary that uniquely predicted PR for fine-structure and envelope filled conditions. These findings suggest that the contribution of lexical knowledge and verbal WM during PR depends crucially on the information content that replaced the silent intervals. When perceptual continuity was partially restored by filler speech noise, both lexical knowledge and verbal WM capacity facilitated PR. Importantly, for fine-structure and envelope filled interrupted conditions, lexical knowledge was crucial for PR.

Sexual Behavior, Risk Compensation, and HIV Prevention Strategies Among Participants in the San Francisco PrEP Demonstration Project: A Qualitative Analysis of Counseling Notes

PubMed Central

Hojilla, J. Carlo; Koester, Kimberly A.; Cohen, Stephanie E.; Buchbinder, Susan; Ladzekpo, Deawodi; Matheson, Tim; Liu, Albert Y

2015-01-01

Pre-exposure prophylaxis (PrEP) is a viable HIV prevention strategy but risk compensation could undermine potential benefits. There are limited data that examine this phenomenon outside of clinical trials. We conducted a qualitative analysis of counseling notes from the San Francisco site of the US PrEP Demonstration Project to assess how men who have sex with men (MSM) used PrEP as a prevention strategy and its impact on their sexual practices. Four major themes emerged from our analysis of 130 distinct notes associated with 26 participants. Prevention strategy decision-making was dynamic, often influenced by the context and perceived risk of a sexual encounter. Counselors noted that participants used PrEP in conjunction with other health promotion strategies like condoms, asking about HIV status of their sex partners, and seroadaptation. With few exceptions, existing risk reduction strategies were not abandoned upon initiation of PrEP. Risk-taking behavior was ‘seasonal’ and fluctuations were influenced by various personal, psychosocial, and health-related factors. PrEP also helped relieve anxiety regarding sex and HIV, particularly among serodiscordant partners. Understanding sexual decision-making and how PrEP is incorporated into existing prevention strategies can help inform future PrEP implementation efforts. PMID:25835463

'I am not a man': Trans-specific barriers and facilitators to PrEP acceptability among transgender women.

PubMed

Sevelius, Jae M; Keatley, JoAnne; Calma, Nikki; Arnold, Emily

2016-01-01

The frequent conflation of transgender ('trans') women with 'men who have sex with men (MSM)' in HIV prevention obscures trans women's unique gender identities, social and behavioural vulnerabilities, and their disproportionately high rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an efficacious biomedical HIV prevention approach. However, trans women are underrepresented in PrEP research, and are often aggregated with MSM without consideration for their unique positions within sociocultural contexts. This study examined PrEP acceptability among trans women via three focus groups and nine individual interviews (total N = 30) in San Francisco. While knowledge of PrEP was low, interest was relatively high once participants were informed. Due to past negative healthcare experiences, ability to obtain PrEP from a trans-competent provider was cited as essential to PrEP uptake and adherence. Participants noted that PrEP could address situations in which trans women experience reduced power to negotiate safer sex, including sex work. Trans-specific barriers included lack of trans-inclusive marketing of PrEP, prioritisation of hormone use, and medical mistrust due to transphobia. Findings underscore the importance of disaggregating trans women from MSM in HIV prevention strategies to mitigate disparate risk among this highly vulnerable population.

Geographic and Individual Associations with PrEP Stigma: Results from the RADAR Cohort of Diverse Young Men Who have Sex with Men and Transgender Women.

PubMed

Mustanski, Brian; Ryan, Daniel T; Hayford, Christina; Phillips, Gregory; Newcomb, Michael E; Smith, Justin D

2018-05-22

Increasing the uptake of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition among at-risk populations, such as young men who have sex with men (YMSM), is of vital importance to slowing the HIV epidemic. Stigma and negative injunctive norms, such as the so called "Truvada Whore" phenomenon, hamper this effort. We examined the prevalence and types of PrEP stigma and injunctive norm beliefs among YMSM and transgender women and associated individual and geospatial factors. A newly created measure of PrEP Stigma and Positive Attitudes was administered to 620 participants in an ongoing longitudinal cohort study. Results indicated lower stigma among White, compared to Black and Latino participants, and among participants not identifying as male. Prior knowledge about PrEP was associated with lower stigma and higher positive attitudes. PrEP stigma had significant geospatial clustering and hotspots were identified in neighborhoods with high HIV incidence and concentration of racial minorities, whereas coldspots were identified in areas with high HIV incidence and low LGBT stigma. These results provide important information about PrEP attitudes and how PrEP stigma differs between individuals and across communities.

Minimal Awareness and Stalled Uptake of Pre-Exposure Prophylaxis (PrEP) Among at Risk, HIV-Negative, Black Men Who Have Sex with Men

PubMed Central

Driffin, Daniel D.; Bauermeister, Jose; Smith, Harlan; Conway-Washington, Christopher

2015-01-01

Abstract In the United States, rates of HIV infection are highest among black men who have sex with men (BMSM). Pre-exposure prophylaxis (PrEP) is a highly effective form of HIV prevention, but the uptake of this strategy has been slow since FDA approval in 2012, and it is unknown whether information about PrEP is reaching BMSM. Four hundred and thirty-six BMSM in Atlanta, GA were surveyed from January 2012 (6 months prior to PrEP approval) to March 2014 (20 months after approval). Analyses revealed no association between date of survey assessment and awareness of PrEP (20.5% were aware of PrEP before approval and 23.4% were aware after approval; OR=0.99 [0.98–1.02], p=0.952). In a multivariate model, BMSM unaware of PrEP reported lower rates of HIV testing knowledge, fewer experiences with HIV testing, and higher rates of transactional sex than BMSM who were aware of PrEP. Our findings suggest that there is limited understanding of PrEP and that there is considerable groundwork that needs to be achieved in order to reap the full benefits of PrEP. The current findings call attention to the need to both prioritize and better understand how to strengthen the bridge between medical advances and community uptake. PMID:26083143

Prion potency in stem cells biology.

PubMed

Lopes, Marilene H; Santos, Tiago G

2012-01-01

Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

Performing the Union: the Prüm Decision and the European dream.

PubMed

Prainsack, Barbara; Toom, Victor

2013-03-01

In 2005, seven European countries signed the so-called Prüm Treaty to increase transnational collaboration in combating international crime, terrorism and illegal immigration. Three years later, the Treaty was adopted into EU law. EU member countries were now obliged to have systems in place to allow authorities of other member states access to nationally held data on DNA, fingerprints, and vehicles by August 2011. In this paper, we discuss the conditions of possibility for the Prüm network to emerge, and argue that rather than a linear ascent towards technological and political convergence and harmonisation, the (hi)story of Prüm is heterogeneous and halting. This is reflected also in the early stages of implementing the Prüm Decision which has proven to be more challenging than it was hoped by the drivers of the Prüm process. In this sense, the Prüm network sits uncomfortably with success stories of forensic science (many of which served the goal of justifying the expansion of technological and surveillance systems). Instead of telling a story of heroic science, the story of Prüm articulates the European dream: one in which goods, services, and people live and travel freely and securely. Copyright © 2012. Published by Elsevier Ltd.

Young and Waltzing Binary Stars

NASA Astrophysics Data System (ADS)

2001-10-01

ADONIS Observes Low-mass Eclipsing System in Orion Summary A series of very detailed images of a binary system of two young stars have been combined into a movie . In merely 3 days, the stars swing around each other. As seen from the earth, they pass in front of each other twice during a full revolution, producing eclipses during which their combined brightness diminishes . A careful analysis of the orbital motions has now made it possible to deduce the masses of the two dancing stars . Both turn out to be about as heavy as our Sun. But while the Sun is about 4500 million years old, these two stars are still in their infancy. They are located some 1500 light-years away in the Orion star-forming region and they probably formed just 10 million years ago . This is the first time such an accurate determination of the stellar masses could be achieved for a young binary system of low-mass stars . The new result provides an important piece of information for our current understanding of how young stars evolve. The observations were obtained by a team of astronomers from Italy and ESO [1] using the ADaptive Optics Near Infrared System (ADONIS) on the 3.6-m telescope at the ESO La Silla Observatory. PR Photo 29a/01 : The RXJ 0529.4+0041 system before primary eclipse PR Photo 29b/01 : The RXJ 0529.4+0041 system at mid-primary eclipse PR Photo 29c/01 : The RXJ 0529.4+0041 system after primary eclipse PR Photo 29d/01 : The RXJ 0529.4+0041 system before secondary eclipse PR Photo 29e/01 : The RXJ 0529.4+0041 system at mid-secondary eclipse PR Photo 29f/01 : The RXJ 0529.4+0041 system after secondary eclipse PR Video Clip 06/01 : Video of the RXJ 0529.4+0041 system Binary stars and stellar masses Since some time, astronomers have noted that most stars seem to form in binary or multiple systems. This is quite fortunate, as the study of binary stars is the only way in which it is possible to measure directly one of the most fundamental quantities of a star, its mass. The mass of a star determines its fate . Massive stars (with masses more than 50 times that of the Sun) lead a glorious, but short life. They are hot and very luminous and exhaust their energy supply in just a few million years. At the other end of the scale, low-mass stars like the Sun are more economical with their resources. Being cooler and dimmer, they are able to shine for billions of years [2]. But although the mass determines the fate of a star, it is not a trivial matter to measure this crucial parameter. In fact, it can only be determined directly if the star happens to be gravitationally bound to another star in a binary stellar system. Observations of the orbital motions of the two stars as they circle each other allows to "weigh" them, and also provide other important information, e.g. about their sizes and temperatures. Orbital motions The understanding of orbital motions has a long history in astronomy. The basic laws of Johannes Kepler (1571-1630) are still used to calculate the masses of orbiting objects, in the solar system as well as in binary stellar systems. However, while the observations of the motion of the nine planets and moons have allowed us to measure quite accurately the masses of objects in our vicinity, the information needed to "weigh" the binary stellar systems is not that easy to obtain. As a result, the mass estimates of the stars in binary systems are often rather uncertain. A main problem is that the individual stars in many binary systems can not be visually separated, even in the best telescopes. The information about the orbit may then come from the motions of the stars, if these are revealed by spectroscopic observations of the combined light (such systems are referred to as "spectroscopic binaries"). If absorption lines from both components are present in the spectrum, the measured wavelength of these double lines will shift periodically back and forth. This is the well-known Doppler effect and it directly reflects the changing velocities of the stars, as they move along their orbits and periodically approach and recede from the observer. Such spectroscopic observations therefore allow to measure the orbital velocities of the stars. It is exactly the same technique that is used to study and weigh extra-solar planets orbiting other stars [3]. However, this method has an important limitation. From the spectroscopical observations alone, it is only possible to deduce limits on the masses, as the inclination of orbits to the line-of-sight is usually unknown. The masses derived in this way (for stars as well as for exoplanets) are therefore only lower limits on the actual masses. Eclipsing Binaries However, fortunate observational circumstances sometimes allow to obtain all information about the stellar orbits. If a binary system is viewed (almost exactly) edge-on, the stars may pass in front of each other from time to time. Astronomers refer to this phenomenon as an "eclipse" and speak about an "eclipsing binary". The effect is similar to a "solar" eclipse as seen on the Earth, whenever the Moon passes in front of the Sun. Like the Moon blocks the sunlight, less light is received from the eclipsed star and thus the combined light from the binary system decreases during the eclipse. The way this happens (astronomers speak about the system's "lightcurve") then provides the additional information about the inclination of the orbit that is needed to determine exactly the stellar masses in a "spectroscopic" binary system. Very accurate values for the stellar diameters and the surface temperatures of the two stars can also be deduced. In short, when a full set of observations is available, it is possible to give a comprehensive description of an eclipsing binary system and its components. Eclipsing, spectroscopic binaries thus represent true cornerstones for the determination of stellar masses , and as such they are fundamental for our understanding of stellar evolution . Rather few such systems are known, but they can also be used to check ("calibrate") other, indirect methods to derive stellar parameters. It is on this background that the first discovery of an eclipsing binary system with two young, solar-like stars is of great interest. The Orion Binary Young stars are not so easy to find. One way is to look for their high-energy emission from a hot corona, created by their enhanced magnetic activity. The object RXJ 0529.4+0041 was first discovered in this way by the X-ray satellite ROSAT. Subsequent optical spectroscopy showed this object to be a young, low-mass spectroscopic binary system. And when a team of astronomers [1] used a 91-cm telescope at the Serra La Nave observing station on the slope of the Etna volcano (Sicily) to monitor the light curve, they also discovered that this system undergoes eclipses. All data confirm that RXJ 0529.4+0041 is located in the Orion Nebula at a distance of about 1500 light-years. This is one of the nearest star-forming regions and almost all stars in this area are quite young. Spectroscopic observations soon confirmed that the binary system was no exception. In particular, fairly strong absorption lines of the fragile element Lithium [4] were detected in both of the binary stars. As Lithium is known to be rapidly destroyed in stars, the finding of a relatively high content of this element implies that the stars must indeed be young. They were probably formed no more than 10 million years ago, i.e., in astronomical terms, they are "infant" stars . High-resolution spectroscopic observations, mostly with the CORALIE spectrometer on the Swiss 1.2-m Leonard Euler telescope at the ESO La Silla Observatory , were used to determine the radial velocities of the stars. From these, a first determination of the orbital and stellar parameters was possible. The orbital period turned out to be short. The two stars swing around each other in just 3 days. This also means they must be very close to each other (but still entirely detached from each other) - the detailed analysis showed that the distance between the two components is only 12 solar radii, or a little more than 8 million kilometres. If you would image yourself standing on the surface of the smaller star, the disk of the companion star would extend some 15° in the sky. This is 30 times larger than our view of the Sun! ADONIS observations The short orbital period and the even shorter duration of the eclipses, only 6 hours, posed a real challenge for the observers. They decided to obtain further high-angular resolution observations with the ADaptive Optics Near Infrared System (ADONIS) on the 3.6-m telescope at the ESO La Silla Observatory. Most fortunately, early ADONIS images demonstrated that this binary stellar system has a third companion, sufficiently far away from the two others to be seen as a separate star by ADONIS. This unexpected bonus made it possible to monitor the light changes of the binary system in great detail, by using the third companion as a convenient "reference" star. In December 2000 and January 2001, detailed ADONIS images of the RXJ 0529.4+0041 system were obtained in three near-infrared filters (the J-, H- and K-bands). ADONIS is equipped with the SHARP II camera and eliminates the adverse image-smearing effects of the atmospheric turbulence in real-time by means of a computer-controlled flexible mirror. As expected, the new, extremely sharp images of RXJ 0529.4+0041 greatly improved the achievable photometric precision. In particular, as the image of the third component was perfectly separated from the others, it did not "contaminate" the derived light curve of the eclipsing binary. The movie Primary eclipse Secondary eclipse ESO PR Photo 29a/01 ESO PR Photo 29a/01 [Preview - JPEG: 375 x 400 pix - 87k] [Normal - JPEG: 750 x 800 pix - 240k] ESO PR Photo 29d/01 ESO PR Photo 29d/01 [Preview - JPEG: 375 x 400 pix - 112k] [Normal - JPEG: 750 x 800 pix - 272k] ESO PR Photo 29b/01 ESO PR Photo 29b/01 [Preview - JPEG: 375 x 400 pix - 90k] [Normal - JPEG: 750 x 800 pix - 240k] ESO PR Photo 29e/01 ESO PR Photo 29e/01 [Preview - JPEG: 375 x 400 pix - 112k] [Normal - JPEG: 750 x 800 pix - 280k] ESO PR Photo 29c/01 ESO PR Photo 29c/01 [Preview - JPEG: 375 x 400 pix - 94k] [Normal - JPEG: 750 x 800 pix - 256k] ESO PR Photo 29f/01 ESO PR Photo 29f/01 [Preview - JPEG: 375 x 400 pix - 112k] [Normal - JPEG: 750 x 800 pix - 280k] Caption : Six individual frames from the ADONIS movie of the RXJ 0529.4+0041 eclipsing, binary stellar system, corresponding to the time around the "primary" and "secondary" eclipses, respectively. For a detailed explanation, read the text. ESO PR Video Clip 06/01 [512 x 448 pix MPEG] ESO PR Video Clip 06/01 (150 frames/00:06 min) [MPEG Video; 512 x 448 pix; 871 k] ESO Video Clip 06/01 shows the ADONIS images of the RXJ 0529.4+0041 eclipsing, binary stellar system, as recorded in three near-infrared filters (J, H, and K; to the left), with the observed light-curves (top) and a graphical representation of the system during a full orbit, as it would look like to a nearby observer. More details in the text The ADONIS images have been combined into an instructive movie ( PR Video Clip 06/01 ). The left-hand panel shows the eclipsing binary system (it is the upper right and brighter of the two objects; the light from the two stars merge into a single point of light) and the well visible third component (lower left), as they were recorded by ADONIS in the three different filter bands. As the two stars in the binary system move around each other in their orbits, eclipses occur and the brightness of the binary system clearly changes - it may help to play the movie several times to see this more clearly. For reference, the Universal Time (UT) and the orbital phase (increasing from 0 to 1 during a full revolution) are continuously displayed in the movie. The right-hand panel shows a build-up of the observed light curves for the binary system. It represents the brightness difference between binary system and the third object that shines with constant light. Both the primary, deeper and the secondary, less deep eclipses are well visible. The primary eclipse was observed on December 8, 2000 and is here displayed at phase zero. During this minimum, the brightness of the binary system decreases by about 45% (0.4 magnitudes). The primary eclipse takes place when the smaller component blocks the light from the brighter and hotter star. The orbital motions of the two stars are illustrated by a computer-generated, animated sequence. The secondary eclipse (at phase 0.5) dims the light from the system less; it occurs when the larger and brighter star almost completely (about 90%) hides its smaller companion. The second minimum was recorded on January 12, 2001. None of the eclipses is therefore "total". The stellar parameters A detailed analysis of these high-precision light curves allowed the astronomers to determine the orbits and hence, to perform an extremely accurate measurement of the fundamental stellar parameters for the two young stars of RXJ 0529.4+0041 . The star that is eclipsed during the primary eclipse (the "primary") is the more massive and also the hotter and brighter of the two stars. Its mass is 1.3 times that of our Sun, i.e., about 2.6 10 30 kg [2]. Its diameter is nearly 1.6 times larger than that of our Sun (i.e., about 2.2 million km) and the surface temperature is found to be a little more than 5000 °C, or a few hundred degrees cooler than the Sun. The "secondary" star is slightly lighter than our Sun. Its weight is about 90% of that of the Sun (1.8 10 30 kg) and the diameter is 20% larger (about 1.7 million km), while the surface temperature is 4000 degrees. In fact, these two stars are still so young that most of their energy comes from the contraction process - the first phase during which they are formed from an interstellar cloud by this process is not yet over and they are still getting smaller. It is by this process that collapsing stars heat up enough to start nuclear burning. When infant stars in RXJ 0529.4+0041 eventually reach middle-age, their sizes will most likely also be quite similar to that of the Sun. The significance of RXJ 0529.4+0041 Few systems are known for which such precise determinations of the stellar parameters have ever been possible - and this binary system represents the first case where both the components are such young stars . A detailed comparison of the derived stellar parameters with current models for the evolution of young stars shows fairly good agreement for the primary component. However, there are certain discrepancies in the case of the secondary component, showing that the current models for the early stages of lower-mass stars must still be refined. More information Part of the results described in this press release are described in more detail in a scientific article ( "RXJ 0529.4+0041: a low-mass pre-main sequence eclipsing-spectroscopic binary" by E. Covino et al.) that has been published in the European research journal Astronomy & Astrophysics (Vol. 361, p. 49). Notes [1] The team consists of Elvira Covino (Principal Investigator), Juan M. Alcalá , Rosita Paladino (all Osservatorio Astronomico di Capodimonte, Napoli, Italy), Antonio Frasca , Santo Catalano , Ettore Marilli (all Osservatorio Astrofisico di Catania, Italy) and Michael Sterzik (ESO-Chile). [2] One solar mass corresponds to 1.99 10 30 kg, or about 330,000 times the mass of the Earth. The Sun is about 4500 million years old and its total lifetime is of the order of 12-13,000 million years. It is an interesting thought that if the Sun would have been somewhat heavier, its total lifetime might have been too short for living organisms to develop on the Earth. In fact, the biological evolution that ultimately lead to the emergence of human beings apparently lasted about 4 billion years; this corresponds to the total lifetime of a star that is only about 20 % heavier than the Sun. Note also the current ESO-ESA CERN educational programme on "Life in the Universe". [3] In the case of exoplanets, the planet itself is not visible, but the spectral lines from the star are seen to wobble due to the gravitational influence of the planet, cf. ESO PR 07/01. [4] Several ESO Press Releases concern observations of the element Lithium in stars, e.g., PR 03/99 (in a giant star), PR 08/00 (in a metal-poor star) and PR 10/01 (from a "swallowed" exoplanet).

La prévention des blessures chez les enfants et les adolescents : une démarche de santé publique

PubMed Central

Yanchar, Natalie L; Warda, Lynne J; Fuselli, Pamela

2012-01-01

RÉSUMÉ La majorité des blessures dont sont victimes les enfants et les adolescents sont évitables. Le présent document de principes contient des renseignements généraux, des conseils et une déclaration d’engagement à l’égard de la prévention des blessures au Canada. Il sert de base sur laquelle construire en s’attardant d’abord aux définitions, à l’étendue et aux priorités en matière de prévention des blessures. Il contient également une description du fardeau et du profil des blessures non intentionnelles, de même que les principes d’interventions de prévention efficaces. La version intégrale renferme une liste de ressources en vue d’obtenir des données et de l’information probante (www.cps.ca). Enfin, le présent document de principes peut être utilisé pour la défense généralisée de la prévention des blessures.

"How I Wish This Thing Was Initiated 100 Years Ago!" Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

PubMed

Karuga, Robinson Njoroge; Njenga, Serah Nduta; Mulwa, Rueben; Kilonzo, Nduku; Bahati, Prince; O'reilley, Kevin; Gelmon, Lawrence; Mbaabu, Stephen; Wachihi, Charles; Githuka, George; Kiragu, Michael

2016-01-01

The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.

TRMM Precipitation Radar Reflectivity Profiles Compared to High-Resolution Airborne and Ground-Based Radar Measurements

NASA Technical Reports Server (NTRS)

Heymsfield, G. M.; Geerts, B.; Tian, L.

1999-01-01

In this paper, TRMM (Tropical Rainfall Measuring Mission Satellite) Precipitation Radar (PR) products are evaluated by means of simultaneous comparisons with data from the high-altitude ER-2 Doppler Radar (EDOP), as well as ground-based radars. The comparison is aimed primarily at the vertical reflectivity structure, which is of key importance in TRMM rain type classification and latent heating estimation. The radars used in this study have considerably different viewing geometries and resolutions, demanding non-trivial mapping procedures in common earth-relative coordinates. Mapped vertical cross sections and mean profiles of reflectivity from the PR, EDOP, and ground-based radars are compared for six cases. These cases cover a stratiform frontal rainband, convective cells of various sizes and stages, and a hurricane. For precipitating systems that are large relative to the PR footprint size, PR reflectivity profiles compare very well to high-resolution measurements thresholded to the PR minimum reflectivity, and derived variables such as bright band height and rain types are accurate, even at high PR incidence angles. It was found that for, the PR reflectivity of convective cells small relative to the PR footprint is weaker than in reality. Some of these differences can be explained by non-uniform beam filling. For other cases where strong reflectivity gradients occur within a PR footprint, the reflectivity distribution is spread out due to filtering by the PR antenna illumination pattern. In these cases, rain type classification may err and be biased towards the stratiform type, and the average reflectivity tends to be underestimated. The limited sensitivity of the PR implies that the upper regions of precipitation systems remain undetected and that the PR storm top height estimate is unreliable, usually underestimating the actual storm top height. This applies to all cases but the discrepancy is larger for smaller cells where limited sensitivity is compounded by incomplete beam filling. Users of level three TRMM PR products should be aware of this scale dependency.

PrP{sup C} displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrP{sup C} knockout mice

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

Bertuchi, Fernanda R.; Bourgeon, Dominique M.G.; Landemberger, Michele C.

2012-02-03

Highlights: Black-Right-Pointing-Pointer PrP{sup C} in solution acts as a radical scavenger. Black-Right-Pointing-Pointer PrP{sup C} reduces hydrogen peroxide toxicity in astrocytes. Black-Right-Pointing-Pointer Increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes. Black-Right-Pointing-Pointer PrP{sup C} prevents the cell death independently of an SOD-like activity. -- Abstract: The PrP{sup C} protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP{sup C} in solution and its participation as a cell protector in astrocytes that weremore » subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP{sup C} decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu{sup 2+}/ascorbate/H{sub 2}O{sub 2}), which was demonstrated by approximately 70% less DMPO/OH{sup {center_dot}}. In cultured PrP{sup C}-knockout astrocytes from mice, the absence of PrP{sup C} caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H{sub 2}O{sub 2} treatment. This rapid increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP{sup C} in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.« less

A qualitative study analyzing access to physical rehabilitation for traffic accident victims with severe disability in Brazil.

PubMed

Sousa, Kelienny de Meneses; Oliveira, Wagner Ivan Fonsêca de; Melo, Laiza Oliveira Mendes de; Alves, Emanuel Augusto; Piuvezam, Grasiela; Gama, Zenewton André da Silva

2017-03-01

Purpose To identify access barriers to physical rehabilitation for traffic accident (TA) victims with severe disability and build a theoretical model to provide guidance towards the improvement of these services. Methods Qualitative research carried out in the city of Natal (Northeast Brazil), with semi-structured interviews with 120 subjects (19 key informer health professionals and 101 TA victims) identified in a database made available by the emergency hospital. The interviews were analyzed using Alceste software, version 4.9. Results The main barriers present in the interviews were: (1) related to services: bureaucratic administrative practises, low offer of rehabilitation services, insufficient information on rehabilitation, lack of guidelines that integrate hospital and ambulatory care and (2) related to patients: financial difficulties, functional limitations, geographic distance, little information on health, association with low education levels and disbelief in the system and in rehabilitation. Conclusion The numerous access barriers were presented in a theoretical model with causes related to organizational structure, processes of care, professionals and patients. This model must be tested by health policy-makers and managers to improve the quality of physical rehabilitation and avoid unnecessary prolongation of the suffering and disability experienced by TA survivors. Implications for rehabilitation Traffic accidents (TAs) are a global health dilemma that demands integrality of preventive actions, pre-hospital and hospital care and physical rehabilitation (PR). This study lays the foundation for improving access to PR for TA survivors, an issue of quality of care that results in preventable disabilities. The words of the patients interviewed reveal the suffering of victims, which is often invisible to society and given low priority by health policies that relegate PR to a second plan ahead of prevention and urgent care. A theoretical model of the causes of the problem of access to PR was built. The identified barriers are potentially preventable through the intervention of health policy-makers, managers, regulators and rehabilitation professionals, and by encouraging the participation of patients. Addressing timely access barriers involves the expansion of the supply of services and rehabilitation professionals, regulation and standardization of referencing practises and encouraging the provision of information to patients about continuity of care and their health needs.

Neural correlates of free recall of "famous events" in a "hypermnestic" individual as compared to an age- and education-matched reference group.

PubMed

Fehr, Thorsten; Staniloiu, Angelica; Markowitsch, Hans J; Erhard, Peter; Herrmann, Manfred

2018-06-19

Memory performance of an individual (within the age range: 50-55 years old) showing superior memory abilities (protagonist PR) was compared to an age- and education-matched reference group in a historical facts ("famous events") retrieval task. Contrasting task versus baseline performance both PR and the reference group showed fMRI activation patterns in parietal and occipital brain regions. The reference group additionally demonstrated activation patterns in cingulate gyrus, whereas PR showed additional widespread activation patterns comprising frontal and cerebellar brain regions. The direct comparison between PR and the reference group revealed larger fMRI contrasts for PR in right frontal, superior temporal and cerebellar brain regions. It was concluded that PR generally recruits brain regions as normal memory performers do, but in a more elaborate way, and furthermore, that he applied a memory-strategy that potentially includes executively driven multi-modal transcoding of information and recruitment of implicit memory resources.

Cellular mechanisms responsible for cell-to-cell spreading of prions.

PubMed

Vilette, Didier; Courte, Josquin; Peyrin, Jean Michel; Coudert, Laurent; Schaeffer, Laurent; Andréoletti, Olivier; Leblanc, Pascal

2018-05-14

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrP Sc ). These abnormal aggregated PrP Sc species multiply in infected cells by recruiting and converting the host PrP C protein into new PrP Sc . How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrP Sc -containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrP Sc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases.

Factors associated with body image dissatisfaction among adolescents in public schools students in Salvador, Brazil.

PubMed

Santana, Mônica L P; Silva, Rita de Cássia R; Assis, Ana M O; Raich, Rosa M; Machado, Maria Ester P C; de J Pinto, Elizabete; de Moraes, Lia T L P; Ribeiro Júnior, Hugo da C

2013-01-01

To identify the prevalence of body image dissatisfaction and associated factors among students in Salvador, Brazil. A cross-sectional study involving a random sample of 1,494 (852 girls and 642 boys) adolescents between 11 and 17 years of age who were students in the public schools in Salvador, Brazil. Participants completed the Body Shape Questionnaire and the Eating Attitudes Test-26. Body image was characterized as satisfactory or unsatisfactory. We obtained demographic, anthropometric and economic information and information regarding the stage of maturation, self-perception of body weight, and consumption of sweetened beverages and diet soft drinks. To identify associated factors we used Poisson regression analysis. Body image dissatisfaction was present in 19.5% of the adolescents, with a prevalence of 26.6% among the girls and 10% among the boys. Independent of sex, the prevalence of body image dissatisfaction was higher among adolescents who were overweight or obese (girls, PR: 1.38, CI: 1.09-1.73 and boys, PR: 2.26, CI: 1.08-4.75), higher among those who perceived themselves as fat (girls, PR: 2.85, CI: 2.07-3.93 and boys, PR: 3.17, CI: 1.39-7.23), and higher among those who had negative attitudes toward eating (girls, PR: 2.42, CI: 1.91-3.08 and boys, PR: 4.67, CI: 2.85-7.63).. A reduction in body image dissatisfaction was only identified among underweight girls (PR: 0.12, CI: 0.03-0.49). A high occurrence of body image dissatisfaction was observed among the adolescents, and biological and behavioral factors were associated with this dissatisfaction. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

C-Terminal Helical Domains of Dengue Virus Type 4 E Protein Affect the Expression/Stability of prM Protein and Conformation of prM and E Proteins

PubMed Central

Tsai, Wen-Yang; Hsieh, Szu-Chia; Lai, Chih-Yun; Lin, Hong-En; Nerurkar, Vivek R.; Wang, Wei-Kung

2012-01-01

Background The envelope (E) protein of dengue virus (DENV) is the major immunogen for dengue vaccine development. At the C-terminus are two α-helices (EH1 and EH2) and two transmembrane domains (ET1 and ET2). After synthesis, E protein forms a heterodimer with the precursor membrane (prM) protein, which has been shown as a chaperone for E protein and could prevent premature fusion of E protein during maturation. Recent reports of enhancement of DENV infectivity by anti-prM monoclonal antibodies (mAbs) suggest the presence of prM protein in dengue vaccine is potentially harmful. A better understanding of prM-E interaction and its effect on recognition of E and prM proteins by different antibodies would provide important information for future design of safe and effective subunit dengue vaccines. Methodology/Principal Findings In this study, we examined a series of C-terminal truncation constructs of DENV4 prME, E and prM. In the absence of E protein, prM protein expressed poorly. In the presence of E protein, the expression of prM protein increased in a dose-dependent manner. Radioimmunoprecipitation, sucrose gradient sedimentation and pulse-chase experiments revealed ET1 and EH2 were involved in prM-E interaction and EH2 in maintaining the stability of prM protein. Dot blot assay revealed E protein affected the recognition of prM protein by an anti-prM mAb; truncation of EH2 or EH1 affected the recognition of E protein by several anti-E mAbs, which was further verified by capture ELISA. The E protein ectodomain alone can be recognized well by all anti-E mAbs tested. Conclusions/Significance A C-terminal domain (EH2) of DENV E protein can affect the expression and stability of its chaperone prM protein. These findings not only add to our understanding of the interaction between prM and E proteins, but also suggest the ectodomain of E protein alone could be a potential subunit immunogen without inducing anti-prM response. PMID:23300717

Laser action of Pr3+ in LiYF4 and spectroscopy of Eu2+-sensitized Pr in BaY2F8

NASA Astrophysics Data System (ADS)

Knowles, David S.; Gabbe, David; Jenssen, H. P.; Zhang, Z.

1988-06-01

Laser action in flashlamp-pumped Pr:LiYF4 at room temperature is observed at 640 nm with a 15-J threshold, but only about 0.01 percent slope efficiency. Increased efficiency from sensitizing the Pr with Eu2+ is explored in the system Eu,Pr:BaY2F8. Codoped samples have been grown by the Czochralski growth method, and energy transfer between 2+ and Pr3+ is observed to be very weak. This is probably due to the poor overlap of the Eu2+ emission with the Pr3+ absorption lines, leading to the conclusion that hosts with a stronger crystal field at the Eu2+ site need to be identified.

Parental perceptions of childhood seasonal influenza vaccination in Singapore: A cross-sectional survey.

PubMed

Low, Mabel S F; Tan, Hweeyong; Hartman, Mikael; Tam, Clarence C; Hoo, Cheehow; Lim, Jiaqing; Chiow, Simin; Lee, Simin; Thng, Renzhi; Cai, Mingzhe; Tan, Yanru; Lock, Jingzhan

2017-10-27

Seasonal influenza vaccination is recommended in children aged 6-59months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore. In December 2015-March 2016, we conducted a survey of 332 parents of children aged 6months to 5years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination. Knowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child's doctor (prevalence ratio (PR)=2.47, 95% CI: 1.75-3.48); receiving influenza vaccine information from a private general practitioner (PR=1.47, 95% CI: 1.05-2.04); regularly receiving pre-travel influenza vaccine (PR=1.64, 95% CI: 1.19-2.25); higher willingness to vaccinate (PR=1.58, 95% CI:1.24-2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR=1.44, 95% CI: 1.04-1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR=0.44, 95% CI: 0.23-0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45vs SGD30, p=0.0012). Knowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.

PubMed

Akasaka, Kazuyuki; Maeno, Akihiro; Murayama, Taichi; Tachibana, Hideki; Fujita, Yuzo; Yamanaka, Hitoki; Nishida, Noriyuki; Atarashi, Ryuichiro

2014-01-01

The crucial step for the fatal neurodegenerative prion diseases involves the conversion of a normal cellular protein, PrP(C), into a fibrous pathogenic form, PrP(Sc), which has an unusual stability against heat and resistance against proteinase K digestion. A successful challenge to reverse the reaction from PrP(Sc) into PrP(C) is considered valuable, as it would give a key to dissolving the complex molecular events into thermodynamic and kinetic analyses and may also provide a means to prevent the formation of PrP(Sc) from PrP(C) eventually in vivo. Here we show that, by applying pressures at kbar range, the "proteinase K-resistant" fibrils (rHaPrP(res)) prepared from hamster prion protein (rHaPrP [23-231]) by seeding with brain homogenate of scrapie-infected hamster, becomes easily digestible. The result is consistent with the notion that rHaPrP(res) fibrils are dissociated into rHaPrP monomers under pressure and that the formation of PrP(Sc) from PrP(C) is thermodynamically controlled. Moreover, the efficient degradation of prion fibrils under pressure provides a novel means of eliminating infectious PrP(Sc) from various systems of pathogenic concern.

Understanding influences on the uptake of pulmonary rehabilitation in the East of England: an Inclusive Design/mixed-methods study protocol

PubMed Central

Dickerson, Terry; Early, Frances; Fuld, Jonathan; Clarkson, P John

2018-01-01

Introduction 1.2 million people in the UK have chronic obstructive pulmonary disease (COPD) that causes breathlessness, difficulty with daily activities, infections and hospitalisation. Pulmonary rehabilitation (PR), a programme of supervised exercise and education, is recommended for patients with COPD. However, only 1 in 10 of those who need it receive PR. Also, the UK National COPD Audit Programme concluded that the COPD treatment might not be accessible to people with disabilities. This paper applies an Inclusive Design approach to community-based PR service provisions. It aims to inform improvements to the PR service by identifying barriers to the uptake of PR in the COPD care journey in relation to patients’ capabilities that can affect their access to PR. Methods and analysis The protocol includes four steps. Step 1 will involve interviews with healthcare professionals and patients to gather insight into their experiences and produce a hierarchical task analysis of the COPD care journeys. Step 2 will estimate the service exclusion: the demand of every task on patients’ capabilities will be rated by predefined scales, and the proportion of the population excluded from the service will be estimated by an exclusion calculator. Step 3 will identify the challenges of the PR service; a framework analysis will guide the data analysis of the interviews and care journey. Step 4 will propose recommendations to help patients manage their COPD care informed by the challenges identified in step 3 and refine recommendations through interviews and focus groups. Ethics and dissemination The Cambridge Central Research Ethics Committee gave the study protocol a positive ethical opinion (17/EE/0136). Study results will be disseminated through peer-reviewed journals, conferences and the British Lung Foundation networks. They will also be fed into a Research for Patient Benefit project on increasing the referral and uptake of PR. PMID:29691248

Improved ferroelectric and photoluminescence properties in Pr3+ substituted Na0.5Bi0.5TiO3 synthesized using hydrothermal route

NASA Astrophysics Data System (ADS)

Goutham, Cilaveni; Kandula, Kumara Raja; Raavi, Sai Santhosh Kumar; Asthana, Saket

2018-04-01

Nanocrystalline Pr3+ substituted NBT was synthesized using hydrothermal technique. Pr3+ modifies the ferroelectric NBT optically active and enhances the electrical properties with small structural changes. Aiming to the development of the bottom up optoelectronic devices this optimized nanoscale Na0.5Bi0.5-xPrxTiO3(x = 0.005) compound is synthesized hydrothermally. X-ray diffraction pattern shows that the system is stabilized in the Rhombohedral (space groupR3c) phase indicating the local strain inhomogeneity. PE loop shows that there is a decrement in the Ec value compared with compounds synthesized using conventional methods. The strong red emission assigned to prominent transition of the Pr3+ ions at 610nm was observed along with weak blue-green emission, indicating the potential use of the system. Energy transfer from host system to Pr3+ ions is responsible for red emission while blue green emission is due to quenching of 3P0 induced by intervalence charge transfer state.

A Method to Retrieve Rainfall Rate over Land from TRMM Observations

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.

2002-01-01

Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) observations over mesoscale convective systems (MCSs) reveal that there are localized maxima in the rain rate with a scale of about 10 to 20 km that represent thunderstorms (Cbs). Some of these Cbs are developing or intense, while others are decaying or weak. These Cbs constitute only about 20 % of the rain area of a given MCS. Outside of Cbs, the average rain rate is much weaker than that within Cbs. From an analysis of the PR data, we find that the spatial distribution of rain and its character, convective or stratiform, is highly inhomogeneous. This complex nature of rain exists on a scale comparable to that of a Cb. The 85 GHz brightness temperature, T85, observations of the TRMM Microwave Imager (TMI) radiometer taken over an MCS reflect closely the PR rain rate pattern over land. Local maxima in rain rate shown by PR are observed as local minima in T85. Where there are no minima in T85, PR observations indicate there is light rain. However, the TMI brightness temperature measurements (Tbs) have poor ability to discriminate convective rain from stratiform rain. For this reason, a TMI rain retrieval procedure that depends primarily on the magnitude of Tbs performs poorly. In order to retrieve rain rate from TMI data on land one has to include the spatial distribution information deduced from the T85 data in the retrieval method. Then, quantitative estimation of rain rate can be accomplished. A TMI rain retrieval method developed along these lines can yield estimates of rain rate and its frequency distribution which agree closely with that given by PR. We find the current TRMM project TMI (Version 5) rain retrieval algorithm on land could be improved with the retrieval scheme developed here. To support the conceptual frame work of the rain retrieval method developed here, a theoretical analysis of the TMI brightness temperatures in convective and stratiform regions is presented.

Molecular approaches to detecting and discriminating among prions, a class of pathogenic molecules(Abstract)

USDA-ARS?s Scientific Manuscript database

Prions (PrPSc)are the pathogens that cause a set of fatal neurological diseases that include scrapie and chronic wasting disease (CWD). They are composed solely of protein and unlike viral, bacterial, or fungal pathogens, the information necessary to convert the normal cellular prion protein (PrPC) ...

A Comparison of Exposure Control Procedures in CATS Using the GPC Model

ERIC Educational Resources Information Center

Leroux, Audrey J.; Dodd, Barbara G.

2016-01-01

The current study compares the progressive-restricted standard error (PR-SE) exposure control method with the Sympson-Hetter, randomesque, and no exposure control (maximum information) procedures using the generalized partial credit model with fixed- and variable-length CATs and two item pools. The PR-SE method administered the entire item pool…

Impact of a Behavioral-Based Intervention on Inspiratory Muscle Training Prescription by a Multidisciplinary Team

ERIC Educational Resources Information Center

Simms, Alanna M.; Li, Linda C.; Geddes, E. Lynne; Brooks, Dina; Hoens, Alison M.; Reid, W. Darlene

2012-01-01

Introduction: Our goal was to compare behavioral- and information-based interventions aimed at increasing prescription of inspiratory muscle training (IMT) for people with chronic obstructive pulmonary disease (COPD) by interdisciplinary teams during pulmonary rehabilitation (PR). Methods: Six hospital PR programs were randomly assigned to a…

The design and integration of retinal CAD-SR to diabetes patient ePR system

NASA Astrophysics Data System (ADS)

Wu, Huiqun; Wei, Yufang; Liu, Brent J.; Shang, Yujuan; Shi, Lili; Jiang, Kui; Dong, Jiancheng

2017-03-01

Diabetic retinopathy (DR) is one of the serious complications of diabetes that could lead to blindness. Digital fundus camera is often used to detect retinal changes but the diagnosis relies too much on ophthalmologist's experience. Based on our previously developed algorithms for quantifying retinal vessels and lesions, we developed a computer aided detection-structured report (CAD-SR) template and implemented it into picture archiving and communication system (PACS). Furthermore, we mapped our CAD-SR into HL7 CDA to integrate CAD findings into diabetes patient electronic patient record (ePR) system. Such integration could provide more quantitative features from fundus image into ePR system, which is valuable for further data mining researches.

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy.

PubMed

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive "combination prevention" programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers' openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy

PubMed Central

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

Background In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. Discussion The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive “combination prevention” programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. Conclusions The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers’ openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation. PMID:27760685

PrEP Chicago: A randomized controlled peer change agent intervention to promote the adoption of pre-exposure prophylaxis for HIV prevention among young Black men who have sex with men.

PubMed

Young, Lindsay E; Schumm, Phil; Alon, Leigh; Bouris, Alida; Ferreira, Matthew; Hill, Brandon; Khanna, Aditya S; Valente, Thomas W; Schneider, John A

2018-02-01

Advances in biomedical prevention strategies such as pre-exposure prophylaxis (PrEP) represent a new opportunity for reducing HIV incidence among young Black men who have sex with men, for whom the number of new HIV infections continues to rise. However, studies have documented low rates of PrEP uptake in this community. Research suggests that the peer networks of young Black men who have sex with men play important roles in their sexual health decisions. PrEP Chicago is a randomized controlled trial network intervention designed to increase PrEP uptake among young Black men who have sex with men living in Chicago. The aims of this study are twofold. Aim 1 is to estimate the effectiveness of a peer change agent intervention for (1) increasing the number of referrals made to a PrEP information line, (2) increasing the rate of PrEP adoption among non-participant peers, and (3) increasing PrEP knowledge, attitudes, and intentions among participants. Aim 2 is to determine the individual and network variables that explain peer change agent effectiveness. PrEP Chicago is a social network intervention that utilizes the influence of peer change agents to link young Black men who have sex with men in Chicago to PrEP. Young Black men who have sex with men were recruited using respondent-driven sampling. Once screened for eligibility, participants were randomly assigned to either one of two treatment sequences: (1) intervention treatment in Year 1 followed by a minimal contact attention control in Year 2 or (2) the minimal contact attention control in Year 1 followed by treatment in Year 2. The treatment consists of a PrEP/peer change agent training workshop followed by booster calls for 12 months. The attention control consists of a sex diary activity designed to help participants assess sexual risk. Psychosocial, sexual health, and network data are collected from all participants at baseline and at 12- and 24-month follow-ups. In total, 423 participants aged 18-35 have been enrolled (more than 100% target enrollment) and have completed baseline data collection. A majority of participants in both intervention and control groups reported having heard of PrEP before enrolling in the study, yet also reported having had no current or prior experience taking PrEP. Statistical analyses await completion of Year 1 of the trial in March 2018. PrEP Chicago addresses a gap in HIV prevention research and intervention design by utilizing the existing social networks among young Black men who have sex with men as mechanisms for information diffusion, behavioral influence, social support, and empowerment. Therefore, interventions that leverage peer influence processes to facilitate PrEP uptake are promising strategies to improve sexual health engagement and overcome disparities in outcomes among this at-risk population.

The purple cauliflower arises from activation of a MYB transcription factor.

PubMed

Chiu, Li-Wei; Zhou, Xiangjun; Burke, Sarah; Wu, Xianli; Prior, Ronald L; Li, Li

2010-11-01

Anthocyanins are responsible for the color of many flowers, fruits, and vegetables. An interesting and unique Purple (Pr) gene mutation in cauliflower (Brassica oleracea var botrytis) confers an abnormal pattern of anthocyanin accumulation, giving the striking mutant phenotype of intense purple color in curds and a few other tissues. To unravel the nature of the Pr mutation in cauliflower, we isolated the Pr gene via a combination of candidate gene analysis and fine mapping. Pr encoded a R2R3 MYB transcription factor that exhibited tissue-specific expression, consistent with an abnormal anthocyanin accumulation pattern in the mutant. Transgenic Arabidopsis (Arabidopsis thaliana) and cauliflower plants expressing the Pr-D allele recapitulated the mutant phenotype, confirming the isolation of the Pr gene. Up-regulation of Pr specifically activated a basic helix-loop-helix transcription factor and a subset of anthocyanin structural genes encoding flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase to confer ectopic accumulation of pigments in the purple cauliflower. Our results indicate that the genetic variation including a Harbinger DNA transposon insertion in the upstream regulatory region of the Pr-D allele is responsible for the up-regulation of the Pr gene in inducing phenotypic change in the plant. The successful isolation of Pr provides important information on the regulatory control of anthocyanin biosynthesis in Brassica vegetables, and offers a genetic resource for development of new varieties with enhanced health-promoting properties and visual appeal.

The Purple Cauliflower Arises from Activation of a MYB Transcription Factor1[W][OA

PubMed Central

Chiu, Li-Wei; Zhou, Xiangjun; Burke, Sarah; Wu, Xianli; Prior, Ronald L.; Li, Li

2010-01-01

Anthocyanins are responsible for the color of many flowers, fruits, and vegetables. An interesting and unique Purple (Pr) gene mutation in cauliflower (Brassica oleracea var botrytis) confers an abnormal pattern of anthocyanin accumulation, giving the striking mutant phenotype of intense purple color in curds and a few other tissues. To unravel the nature of the Pr mutation in cauliflower, we isolated the Pr gene via a combination of candidate gene analysis and fine mapping. Pr encoded a R2R3 MYB transcription factor that exhibited tissue-specific expression, consistent with an abnormal anthocyanin accumulation pattern in the mutant. Transgenic Arabidopsis (Arabidopsis thaliana) and cauliflower plants expressing the Pr-D allele recapitulated the mutant phenotype, confirming the isolation of the Pr gene. Up-regulation of Pr specifically activated a basic helix-loop-helix transcription factor and a subset of anthocyanin structural genes encoding flavonoid 3’-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase to confer ectopic accumulation of pigments in the purple cauliflower. Our results indicate that the genetic variation including a Harbinger DNA transposon insertion in the upstream regulatory region of the Pr-D allele is responsible for the up-regulation of the Pr gene in inducing phenotypic change in the plant. The successful isolation of Pr provides important information on the regulatory control of anthocyanin biosynthesis in Brassica vegetables, and offers a genetic resource for development of new varieties with enhanced health-promoting properties and visual appeal. PMID:20855520

Experimental Investigation of the Cd-Pr Phase Diagram

PubMed Central

Reichmann, Thomas L.; Effenberger, Herta S.; Ipser, Herbert

2014-01-01

The complete Cd-Pr equilibrium phase diagram was investigated with a combination of powder-XRD, SEM and DTA. All intermetallic compounds within this system, already reported in literature, could be confirmed: CdPr, Cd2Pr, Cd3Pr, Cd45Pr11, Cd58Pr13, Cd6Pr and Cd11Pr. The corresponding phase boundaries were determined at distinct temperatures. The homogeneity range of the high-temperature allotropic modification of Pr could be determined precisely and a limited solubility of 22.1 at.% Cd was derived. Additionally, single-crystal X-ray diffraction was employed to investigate structural details of Cd2Pr; it is isotypic to the AlB2-type structure with a z value of the Cd site of 0.5. DTA results of alloys located in the adjacent two-phase fields of Cd2Pr suggested a phase transformation between 893 and 930°C. For the phase Cd3Pr it was found that the lattice parameter a changes linearly with increasing Cd content, following Vegard’s rule. The corresponding defect mechanism could be evaluated from structural data collected with single-crystal XRD. Introduction of a significant amount of vacancies on the Pr site and the reduction in symmetry of one Cd position (8c to 32f) resulted in a noticeable decrease of all R-values. PMID:24718502

Active FOXO1 is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming

PubMed Central

Diep, Caroline H.; Knutson, Todd P.; Lange, Carol A.

2015-01-01

Progesterone promotes differentiation coupled to proliferation and pro-survival in the breast, but inhibits estrogen-driven growth in the reproductive tract and ovaries. Herein, it is demonstrated, using progesterone receptor (PR) isoform-specific ovarian cancer model systems, that PR-A and PR-B promote distinct gene expression profiles that differ from PR-driven genes in breast cancer cells. In ovarian cancer models, PR-A primarily regulates genes independently of progestin, while PR-B is the dominant ligand-dependent isoform. Notably, FOXO1 and the PR/FOXO1 target-gene p21 (CDKN1A) are repressed by PR-A, but induced by PR-B. In the presence of progestin, PR-B, but not PR-A, robustly induced cellular senescence via FOXO1-dependent induction of p21 and p15 (CDKN2B). Chromatin immunoprecipitation (ChIP) assays performed on PR-isoform specific cells demonstrated that while each isoform is recruited to the same PRE-containing region of the p21 promoter in response to progestin, only PR-B elicits active chromatin marks. Overexpression of constitutively active FOXO1 in PR-A-expressing cells conferred robust ligand-dependent upregulation of the PR-B target genes GZMA, IGFBP1, and p21, and induced cellular senescence. In the presence of endogenous active FOXO1, PR-A was phosphorylated on Ser294 and transactivated PR-B at PR-B target genes; these events were blocked by the FOXO1 inhibitor (AS1842856). PR isoform-specific regulation of the FOXO1/p21 axis recapitulated in human primary ovarian tumor explants treated with progestin; loss of progestin sensitivity correlated with high AKT activity. PMID:26577046

Preparing for PrEP: Perceptions and Readiness of Canadian Physicians for the Implementation of HIV Pre-Exposure Prophylaxis

PubMed Central

Sharma, Malika; Wilton, James; Senn, Heather; Fowler, Shawn; Tan, Darrell H. S.

2014-01-01

Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, but concerns persist around its use. Little is known about Canadian physicians' knowledge of and willingness to prescribe PrEP. We disseminated an online survey to Canadian family, infectious disease, internal medicine, and public health physicians between September 2012–June 2013 to determine willingness to prescribe PrEP. Criteria for analysis were met by 86 surveys. 45.9% of participants felt “very familiar” with PrEP, 49.4% felt that PrEP should be approved by Health Canada, and 45.4% of respondents were willing to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95% confidence interval, CI = 1.6–10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3–19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5–10.5) were positively associated with willingness to prescribe PrEP on univariable analysis. The latter two were the strongest predictors on multivariate analysis. Participants cited cost and efficacy as major concerns. 75.3% did not feel that information had been adequately disseminated among physicians. In summary, Canadian physicians demonstrate varying levels of support for PrEP and express concerns about its implementation. Further research on real-world effectiveness, continuing medical education, and clinical support is needed to prepare physicians for this prevention strategy. PMID:25133648

Knowledge, Practices, and Barriers to HIV Pre-Exposure Prophylaxis (PrEP) Prescribing Among Washington State Medical Providers.

PubMed

Wood, Brian R; McMahan, Vanessa M; Naismith, Kelly; Stockton, Jonathan B; Delaney, Lori A; Stekler, Joanne D

2018-01-04

We aimed to assess HIV pre-exposure prophylaxis (PrEP) awareness and prescribing practices among Washington State medical providers from diverse professional disciplines and practice types. In May 2016, we administered an anonymous online survey to licensed medical practitioners who provide primary, longitudinal, walk-in, emergency, obstetric, gynecologic, sexually transmitted infection (STI), or family planning care. Of 735 eligible providers, 64.8% had heard of PrEP. Younger providers and providers with a Doctor of Medicine (MD) degree were more likely to be aware of PrEP compared to older providers (p=0.0001) and providers of other training backgrounds (Advanced Registered Nurse Practitioner [ARNP], Doctor of Osteopathic Medicine [DO], or Physician Assistant [PA]) (p=0.04). Among providers aware of PrEP, most frequent reported concerns about prescribing were adherence (46.0%) and costs (42.9%). Providers felt very (20.1%) or somewhat (33.8%) comfortable discussing PrEP overall, but very (26.8%) or somewhat (44.7%) uncomfortable discussing cost and insurance issues. The 124 PrEP prescribers reported a median of 2 (range 1-175, total 1,142) patients prescribed PrEP. Prior authorizations and insurance denials had prevented prescriptions for 28.7% and 12.1% of prescribers, respectively. Interventions to improve PrEP access should include education to inform medical providers about PrEP, with particular attention to provider types less likely to be aware. Continued efforts to eliminate cost and insurance barriers and educate providers regarding financial resources would help improve PrEP access.

COPD: Health Care Utilisation Patterns with Different Disease Management Interventions.

PubMed

Luk, Edwin K; Hutchinson, Anastasia F; Tacey, Mark; Irving, Louis; Khan, Fary

2017-08-01

The management of COPD is a significant and costly issue worldwide, with acute healthcare utilisation consisting of admissions and outpatient attendances being a major contributor to the cost. Pulmonary rehabilitation (PR) and integrated disease management (IDM) are often offered. Whilst there is strong evidence of physical and quality of life outcomes following IDM and PR, few studies have looked into healthcare utilisation. The aims of this study were to confirm whether IDM and PR reduce acute healthcare utilisation and to identify factors which contribute to acute health care utilisation or increased mortality. This was a retrospective cohort study of patients with COPD who were referred to IDM over a 10-year period. Patients were also offered an 8-week PR program. Data collected were matched with the hospital dataset to obtain information on inpatient, ED and outpatient attendances. 517 patients were enrolled to IDM. 315 (61%) also commenced PR and 220 (43%) completed PR. Patients who were referred to PR were younger and had less comorbidities (p < 0.001). Both groups (IDM only and IDM + PR referred) had reductions in healthcare utilisation but the IDM-only group had greater reductions. A survival benefit (HR 0.68, 95% CI 0.50-0.92) was seen in those who were PR completers compared to patients who received IDM only. Patients with COPD who successfully complete PR in addition to participating in IDM have improved survival. IDM alone was effective in the reduction of healthcare utilisation; however, the addition of PR did not reduce healthcare usage further.

Potential Link between the Sphingosine-1-Phosphate (S1P) System and Defective Alveolar Macrophage Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

PubMed Central

Barnawi, Jameel; Tran, Hai; Jersmann, Hubertus; Pitson, Stuart; Roscioli, Eugene; Hodge, Greg; Meech, Robyn; Haberberger, Rainer; Hodge, Sandra

2015-01-01

Introduction We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke. The exact mechanisms for this defect are unknown. Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function. Methods We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR. Phagocytosis of apoptotic cells was investigated using flow cytometry. Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD. To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5. The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model. Results We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls. S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD “disease effect” rather than smoke effect per se. Significant associations were noted between S1PR5 and both lung function and phagocytosis. Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages. Antagonising SIPR5 significantly improved phagocytosis. Conclusion Our results suggest a potential link between the S1P signalling system and defective macrophage phagocytic function in COPD and advise therapeutic targets. PMID:26485657

Altered Gag Polyprotein Cleavage Specificity of Feline Immunodeficiency Virus/Human Immunodeficiency Virus Mutant Proteases as Demonstrated in a Cell-Based Expression System

PubMed Central

Lin, Ying-Chuan; Brik, Ashraf; de Parseval, Aymeric; Tam, Karen; Torbett, Bruce E.; Wong, Chi-Huey; Elder, John H.

2006-01-01

We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with a focus on human immunodeficiency virus type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in the active site of FIV PR with structurally equivalent residues of HIV-1 PR dramatically altered the specificity of the mutant PRs in in vitro analyses. Here, we have expanded these studies to analyze the specificity changes in each mutant FIV PR expressed in the context of the natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared in which 4 to 12 HIV-1-equivalent substitutions were made in FIV PR, and cleavage of each Gag-Pol polyprotein was then assessed in pseudovirions from transduced cells. The findings demonstrated that, as with in vitro analyses, inhibitor specificities of the mutants showed increased HIV-1 PR character when analyzed against the natural substrate. In addition, all of the mutant PRs still processed the FIV polyprotein but the apparent order of processing was altered relative to that observed with wild-type FIV PR. Given the importance of the order in which Gag-Pol is processed, these findings likely explain the failure to produce infectious FIVs bearing these mutations. PMID:16873240

Functional analysis of a pathogenesis-related thaumatin-like protein gene TaLr35PR5 from wheat induced by leaf rust fungus.

PubMed

Zhang, Jiarui; Wang, Fei; Liang, Fang; Zhang, Yanjun; Ma, Lisong; Wang, Haiyan; Liu, Daqun

2018-05-04

Plants have evolved multifaceted defence mechanisms to resist pathogen infection. Production of the pathogenesis-related (PR) proteins in response to pathogen attack has been implicated in plant disease resistance specialized in systemic-acquired resistance (SAR). Our earlier studies have reported that a full length TaLr35PR5 gene, encoding a protein exhibiting amino acid and structural similarity to a sweet protein thaumatin, was isolated from wheat near-isogenic line TcLr35. The present study aims to understand the function of TaLr35PR5 gene in Lr35-mediated adult resistance to Puccinia triticina. We determined that the TaLr35PR5 protein contained a functional secretion peptide by utilizing the yeast signal sequence trap system. Using a heterologous expression assay on onion epidermal cells we found that TaLr35PR5 protein was secreted into the apoplast of onion cell. Expression of TaLr35PR5 was significantly reduced in BSMV-induced gene silenced wheat plants, and pathology test on these silenced plants revealed that Lr35-mediated resistance phenotype was obviously altered, indicating that Lr35-mediated resistance was compromised. All these findings strongly suggest that TaLr35PR5 is involved in Lr35-mediated adult wheat defense in response to leaf rust attack.

HIV-negative male couples' attitudes about pre-exposure prophylaxis (PrEP) and using PrEP with a sexual agreement.

PubMed

Mitchell, Jason W; Lee, Ji-Young; Woodyatt, Cory; Bauermeister, José; Sullivan, Patrick; Stephenson, Rob

2016-08-01

One efficacious strategy to help prevent HIV is oral pre-exposure prophylaxis (PrEP), a daily regimen of antiretroviral treatment taken by HIV-negative individuals. Two of the recommendations of Centers for Disease Control and Prevention (CDC) guidelines for PrEP pertain to being in a relationship (i.e., male couples). Despite the recognition of how primary partners in male couples' relationships shape HIV risk and CDC's PrEP guidelines, there is a paucity of data that examine HIV-negative male couples' attitudes toward PrEP use and using PrEP with a sexual agreement. A sexual agreement is an explicit agreement made between two individuals about what sex and other related behaviors may occur within and outside of their relationship. In this qualitative study, we examine HIV-negative male couples' attitudes toward PrEP use and whether they thought PrEP could be integrated into a sexual agreement. Data for this study are drawn from couple-level interviews conducted in 2014 with 29 HIV-negative male couples who had a sexual agreement and were from Atlanta or Detroit. Both passive (e.g., flyers) and active (e.g., targeted Facebook advertisements) recruitment methods were used; the sample was stratified by agreement type. Thematic analysis was applied to identify the following themes regarding HIV-negative male couples' attitudes toward PrEP use: (1) PrEP and condom use; (2) concerns about PrEP (e.g., effectiveness, side effects, and promoting sexually risky behavior); and (3) accessibility of PrEP. Some thought PrEP could be a part of couples' agreement because it could help reduce sexual anxiety and sexual risk, and would help keep the couple safe. Others described PrEP use with an agreement as something for "others". Some were also concerned that incorporating PrEP could usurp the need for a sexual agreement in a couples' relationship. These themes highlight the need to improve informational messaging and promotion efforts about PrEP among HIV-negative male couples who may benefit from using it.

Methodical thermolysis of [Ba2Ti2(thd)4(OnPr)8(nPrOH)2] under autogenous pressure followed by combustion for the synthesis of dielectric tetragonal BaTiO3 nanopowder.

PubMed

Pol, Vilas G; Thiyagarajan, P; Moreno, Jose M Calderon; Popa, Monica; Kessler, Vadim G; Gohil, Suresh; Seisenbaeva, Gulaim A

2009-07-06

The tetragonal BaTiO(3) nanopowder is synthesized in a solvent-less, efficient process by the thermolysis of a single [Ba(2)Ti(2)(thd)(4)(OnPr)(8)(nPrOH)(2)] precursor in a closed reactor at 700 degrees C under autogenous pressure, followed by combustion. This paper compiles the synthesis of the [Ba(2)Ti(2)(thd)(4)(OnPr)(8)(nPrOH)(2)] precursor, its analysis by mass spectrometry, and implementation for the fabrication of dielectric tetragonal BaTiO(3) nanopowder by controlled efficient thermal decomposition. The as-prepared, intermediate, and final forms of the obtained nanomaterials are systematically analysed by XRD, Raman, and EDS measurements to gain structural and compositional information. Employing HR-SEM, TEM, and HR-TEM techniques, the morphological changes during the structural evolution of all the phases are pursued. The mechanistic elucidation for the fabrication of BaTiO(3) nanopowder is developed on the basis of TGA and DTA data obtained for the initial [Ba(2)Ti(2)(thd)(4)(OnPr)(8)(nPrOH)(2)] reactant as well as the as-prepared BaCO(3) with amorphous Ti phase.

Using Intervention Mapping to Develop Health Education Components to Increase Colorectal Cancer Screening in Puerto Rico.

PubMed

Serra, Yolanda A; Colón-López, Vivian; Savas, Lara S; Vernon, Sally W; Fernández-Espada, Natalie; Vélez, Camille; Ayala, Alelí; Fernández, María E

2017-01-01

Colorectal cancer (CRC) is a leading cause of cancer-related mortality in Puerto Rico (PR). Although largely preventable through screening and treatment of precancerous polyps, CRC screening rates in PR remain low while CRC incidence and mortality continue to increase. We used intervention mapping (IM), a systematic framework using theory and evidence to plan a health promotion intervention to increase colorectal cancer screening (CRCS) among Puerto Rican adults 50 years and older who are patients of Federally Qualified Health Centers (FQHCs) in PR. To inform the development of a logic model of the problem during the needs assessment phase, we determined the CRC incidence and mortality rates in PR using recent data from the PR Cancer Registry, conducted a literature review to better understand behavioral and environmental factors influencing CRC among Hispanics in general and in Puerto Ricans, and collected new data. We conducted seven focus groups to identify community needs and resources, specific sub-behaviors related to CRCS (performance objectives) and the determinants of CRCS. We then developed matrices of change objectives that would guide the content, behavioral change method selection, and the practical applications that would be included in the program. We selected two overarching methods: entertainment education and behavioral journalism and developed practical applications, materials, and messages containing several other methods including modeling, persuasion, information, and tailoring. We developed and pretested a Tailored Interactive Multimedia Intervention, newsletter, an action plan, and supplemental print materials for patients. We also developed a patient mediated provider prompt to increase provider recommendation and improve patient provider communication. The use of IM for systematic planning produced a detailed coherent plan for the CRCS educational intervention. Guided by IM processes, steps, and tasks, we used community level information, existing literature, theory, and new data to develop health education materials that were well received by the priority population and will likely increase CRCS among FQHC patients in PR.

Biochemical Characterization of Prions.

PubMed

Fiorini, Michele; Bongianni, Matilde; Monaco, Salvatore; Zanusso, Gianluigi

2017-01-01

Prion disease or transmissible spongiform encephalopathies are characterized by the presence of the abnormal form of the prion protein (PrP Sc ). The pathological and transmissible properties of PrP Sc are enciphered in its secondary and tertiary structures. Since it's well established that different strains of prions are linked to different conformations of PrP Sc , biochemical characterization of prions seems a preliminary but reliable approach to detect, analyze, and compare prion strains. Experimental biochemical procedures might be helpful in distinguishing PrP Sc physicochemical properties and include resistance to proteinase K (PK) digestion, insolubility in nonionic detergents, PK-resistance under denaturing conditions and sedimentation properties in sucrose gradients. This biochemical approach has been extensively applied in human prion disorders and subsequently expanded for PrP Sc characterization in animals. In particular, in sporadic Creutzfedlt-Jakob disease (sCJD) PrP Sc is characterized by two main glycotypes conventionally named Type 1 and Type 2, based on the apparent gel migration at 21 and 19kDa of the PrP Sc PK-resistant fragment. An additional PrP Sc type was identified in sCJD characterized by an unglycosylated dominant glycoform pattern and in 2010 a variably protease-sensitive prionopathy (VPSPr) was reported showing a PrP Sc with an electrophoretic ladder like pattern. Additionally, the presence of PrP Sc truncated fragments completes the electrophoretic characterization of different prion strains. By two-dimensional (2D) electrophoretic analysis additional PrP Sc pattern was identified, since this procedure provides information about the isoelectric point and the different peptides length related to PK cleavage, as well as to glycosylation extent or GPI anchor presence. We here provide and extensive review on PrP Sc biochemical analysis in human and animal prion disorders. Further, we show that PrP Sc glycotypes observed in CJD share similarities with PrP Sc in bovine spongiform encephalopathy forms (BSE). © 2017 Elsevier Inc. All rights reserved.

Induction of SA-signaling pathway and ethylene biosynthesis in Trichoderma harzianum-treated tomato plants after infection of the root-knot nematode Meloidogyne incognita.

PubMed

Leonetti, Paola; Zonno, Maria Chiara; Molinari, Sergio; Altomare, Claudio

2017-04-01

Salicylic acid-signaling pathway and ethylene biosynthesis were induced in tomato treated with Trichoderma harzianum when infected by root-knot nematodes and limited the infection by activation of SAR and ethylene production. Soil pre-treatment with Trichoderma harzianum (Th) strains ITEM 908 (T908) and T908-5 decreased susceptibility of tomato to Meloidogyne incognita, as assessed by restriction in nematode reproduction and development. The effect of T. harzianum treatments on plant defense was detected by monitoring the expression of the genes PR-1/PR-5 and JERF3/ACO, markers of the SA- and JA/ET-dependent signaling pathways, respectively. The compatible nematode-plant interaction in absence of fungi caused a marked suppression of PR-1, PR-5, and ACO gene expressions, either locally or systemically, whilst expression of JERF3 gene resulted unaffected. Conversely, when plants were pre-treated with Th-strains, over-expression of PR-1, PR-5, and ACO genes was observed in roots 5 days after nematode inoculation. JERF3 gene expression did not change in Th-colonized plants challenged with nematodes. In the absence of nematodes, Trichoderma-root interaction was characterized by the inhibition of both SA-dependent signaling pathway and ET biosynthesis, and, in the case of PR-1 and ACO genes, this inhibition was systemic. JERF3 gene expression was systemically restricted only at the very early stages of plant-fungi interaction. Data presented indicate that Th-colonization primed roots for Systemic Acquired Resistance (SAR) against root-knot nematodes and reacted to nematode infection more efficiently than untreated plants. Such a response probably involves also activation of ET production, through an augmented transcription of the ACO gene, which encodes for the enzyme catalyzing the last step of ET biosynthesis. JA signaling and Induced Systemic Resistance (ISR) do not seem to be involved in the biocontrol action of the tested Th-strains against RKNs.

Brief Report: PrEP Uptake, Adherence, and Discontinuation Among California YMSM Using Geosocial Networking Applications.

PubMed

Holloway, Ian W; Dougherty, Ryan; Gildner, Jennifer; Beougher, Sean C; Pulsipher, Craig; Montoya, Jorge A; Plant, Aaron; Leibowitz, Arleen

2017-01-01

We investigated pre-exposure prophylaxis (PrEP) uptake, adherence, and discontinuation among young app-using men who have sex with men in California (N = 761). Approximately, 9.7% of participants had ever used PrEP; 87% of those deemed good candidates for screening (indicated by a Centers for Disease Control and Prevention risk index score ≥10) were not current or past users. PrEP use was associated with higher income [adjusted odds ratio (aOR): 4.13; confidence interval (CI): 1.87 to 9.12], receptive condomless anal sex (aOR: 3.41; CI: 1.71 to 6.78), HIV-positive sex partners (aOR: 2.87; CI: 1.53 to 5.38), popper use (aOR: 3.47; CI: 1.96 to 6.13), and recent sexually transmitted infection diagnosis (aOR: 2.90; CI: 1.64 to 5.13). Some users (41.5%) wanted help remembering to take PrEP. The top reason for discontinuation was concern about long-term side effects (33.0%). Young men who have sex with men app users are prime candidates for PrEP, despite low uptake. Apps may be useful tools for PrEP information dissemination, adherence monitoring, and support.

WebPrInSeS: automated full-length clone sequence identification and verification using high-throughput sequencing data.

PubMed

Massouras, Andreas; Decouttere, Frederik; Hens, Korneel; Deplancke, Bart

2010-07-01

High-throughput sequencing (HTS) is revolutionizing our ability to obtain cheap, fast and reliable sequence information. Many experimental approaches are expected to benefit from the incorporation of such sequencing features in their pipeline. Consequently, software tools that facilitate such an incorporation should be of great interest. In this context, we developed WebPrInSeS, a web server tool allowing automated full-length clone sequence identification and verification using HTS data. WebPrInSeS encompasses two separate software applications. The first is WebPrInSeS-C which performs automated sequence verification of user-defined open-reading frame (ORF) clone libraries. The second is WebPrInSeS-E, which identifies positive hits in cDNA or ORF-based library screening experiments such as yeast one- or two-hybrid assays. Both tools perform de novo assembly using HTS data from any of the three major sequencing platforms. Thus, WebPrInSeS provides a highly integrated, cost-effective and efficient way to sequence-verify or identify clones of interest. WebPrInSeS is available at http://webprinses.epfl.ch/ and is open to all users.

WebPrInSeS: automated full-length clone sequence identification and verification using high-throughput sequencing data

PubMed Central

Massouras, Andreas; Decouttere, Frederik; Hens, Korneel; Deplancke, Bart

2010-01-01

High-throughput sequencing (HTS) is revolutionizing our ability to obtain cheap, fast and reliable sequence information. Many experimental approaches are expected to benefit from the incorporation of such sequencing features in their pipeline. Consequently, software tools that facilitate such an incorporation should be of great interest. In this context, we developed WebPrInSeS, a web server tool allowing automated full-length clone sequence identification and verification using HTS data. WebPrInSeS encompasses two separate software applications. The first is WebPrInSeS-C which performs automated sequence verification of user-defined open-reading frame (ORF) clone libraries. The second is WebPrInSeS-E, which identifies positive hits in cDNA or ORF-based library screening experiments such as yeast one- or two-hybrid assays. Both tools perform de novo assembly using HTS data from any of the three major sequencing platforms. Thus, WebPrInSeS provides a highly integrated, cost-effective and efficient way to sequence-verify or identify clones of interest. WebPrInSeS is available at http://webprinses.epfl.ch/ and is open to all users. PMID:20501601

An Evaluation of a New Format for Presenting Ejection Information in a NATOPS Manual.

DTIC Science & Technology

1979-11-01

Assessment-the subject’s awareness of ejection system limits and knowledge of the specific principles and relationships involved in the ejection decision...percti & le pilot ejecting cannern tintiong onfigursesan at~ 71 knete arrtaeei.l From" th front cockpit. c. Normal aircraft pitc For conditions shown it...40) Arlington, VA 22209 700 Robbins Avenue * 1 CDR P.R. Chatelier Philadelphia, PA 19111 Office of the Undersecretary of Defense for Research

Bayesian Inference for Source Term Estimation: Application to the International Monitoring System Radionuclide Network

DTIC Science & Technology

2014-10-01

de l’exactitude et de la précision), comparativement au modèle de mesure plus simple qui n’utilise pas de multiplicateurs. Importance pour la défense...3) Bayesian experimental design for receptor placement in order to maximize the expected information in the measured concen- tration data for...applications of the Bayesian inferential methodology for source recon- struction have used high-quality concentration data from well- designed atmospheric

14. Photocopy of drawing (this photograph is an 8''x 10'' ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. Photocopy of drawing (this photograph is an 8''x 10'' contact print; November 1, 1993 revision of a May, 1982 as built drawing by M. Villafane, in possession of the Highway System Administration Office of the Puerto Rico Highway and Transportation Authority) Bridge over Perdomo Channel, Road no. P.R.2, Km. 75.60, Arecibo, P.R. no. 2 of 3. - Puente del Cano Perdomo, Route PR-2 spanning Cano Perdomo Channel, Arecibo, Arecibo Municipio, PR

15. Photocopy of drawing (this photograph is an 8''x 10'' ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. Photocopy of drawing (this photograph is an 8''x 10'' contact print; November 1, 1993 revision of a May, 1982 as built drawing by M. Villafane, in possession of the Highway System Administration Office of the Puerto Rico Highway and Transportation Authority) Bridge over Perdomo Channel, Road no. P.R.2, Km. 75.60, Arecibo, P.R. no. 3 of 3. - Puente del Cano Perdomo, Route PR-2 spanning Cano Perdomo Channel, Arecibo, Arecibo Municipio, PR

13. Photocopy of drawing (this photograph is an 8''x 10'' ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. Photocopy of drawing (this photograph is an 8''x 10'' contact print; November 1, 1993 revision of a May, 1982 as built drawing by M. Villafane, in possession of the Highway System Administration Office of the Puerto Rico Highway and Transportation Authority) Bridge over Perdomo Channel, Road no. P.R.2, Km. 75.60, Arecibo, P.R. no. 1 of 3. - Puente del Cano Perdomo, Route PR-2 spanning Cano Perdomo Channel, Arecibo, Arecibo Municipio, PR

Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project.

PubMed

Vaccher, Stefanie J; Gianacas, Christopher; Templeton, David J; Poynten, Isobel M; Haire, Bridget G; Ooi, Catriona; Foster, Rosalind; McNulty, Anna; Grulich, Andrew E; Zablotska, Iryna B

2017-01-01

The effectiveness of daily pre-exposure prophylaxis (PrEP) is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM). This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project. Individuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day), event-driven (pills taken only around specific risk events), or periodic (daily dosing during periods of increased risk). Overall, 315 GBM (98% of study sample) provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95% confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76)]. Individuals' preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to study participants. Further research investigating how behaviours and PrEP preferences change correspondingly over time is needed. ClinicalTrials.gov NCT02206555. Registered 28 July 2014.

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages.

PubMed

Liang, Jiuxing; Zhang, Xiangmin; He, Xiaomin; Ling, Li; Zeng, Chunyao; Luo, Yuxi

2018-05-10

During sleep, respiratory events readily modulate the autonomic nervous system (ANS). Whether such modulation is caused by the respiratory event itself or the cortical arousal that follows and whether these influences differ across sleep stages are not clear. Thus, we aimed to study the independent and combined effects of respiratory events and cortical arousals on the ANS across sleep stages. We recruited 22 male patients with sleep apnea-hypopnea syndrome (SAHS) and analyzed the differences in the indices of heart rate variability among normal respiration (NR), pathological respiratory events without cortical arousals (PR), cortical arousals without respiratory events (CA), and the coexistence of PR and CA (PR&CA), by sleep stage. Compared with NR, four indices of variation of the beat-to-beat interval demonstrated consistent results in all sleep stages generally: PR&CA showed the biggest difference, followed by PR and followed by CA, which exhibited the least difference. Thus, the respiratory event itself affects ANS modulation, but the cortical arousal that follows generally enhances this effect. For low-frequency power and low-frequency/high-frequency power ratio (LF/HF), PR&CA had the greatest impact. For mean beat-to-beat interval and high-frequency power (HFP), the influence of PR, CA, and PR&CA depended on sleep depth. However, PR&CA had a different influence on HFP in N2 stage vs. REM stage. Sleep stage also has an effect on this neuromodulatory mechanism. These findings may help clarify the relationship between SAHS and cardiovascular disease.

Relationships between PrPSc stability and incubation time for United States scrapie strains in a natural host system

USDA-ARS?s Scientific Manuscript database

Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP**C) into a beta-rich conformer (PrP**Sc) that accumulates into higher-order structures in the brain and other ti...

Review and Synthesis of Evidence Regarding Environmental Risks Posed by Munitions Constituents (MC) in Aquatic Systems

DTIC Science & Technology

2017-10-31

default. Cover Image: Munitions response diver approaching an unexploded 1,000 pound General Purpose Bomb at Bahia Salina del Sur (Island of Vieques, PR...30 4.4 Isla de Vieques bombing range (PR, USA...Isla de Vieques Bombing Range site (PR)................................................................ 46 5.2.2 Halifax Harbor (Halifax, Canada

Hardware requirements: A new generation partial reflection radar for studies of the equatorial mesosphere

NASA Technical Reports Server (NTRS)

Vincent, R. A.

1986-01-01

A new partial reflection (PR) radar is being developed for operation at the proposed Equatorial Observatory. The system is being designed to make maximum use of recent advances in solid-state technology in order to minimize the power requirements. In particular, it is planned to use a solid-state transmitter in place of the tube transmitters previously used in PR systems. Solid-state transmitters have the advantages that they do not need high voltage supplies, they do not require cathode heaters with a corresponding saving in power consumption and parts are readily available and inexpensive. It should be possible to achieve 15 kW peak powers with recently announced fast switching transistors. Since high mean powers are desirable for obtaining good signal-to-noise ratios, it is also planned to phase code the transmitted pulses and decode after coherent integration. All decoding and signal processing will be carried out in dedicated microprocessors before the signals are passed to a microcomputer for on-line analysis. Recent tests have shown that an Olivetti M24 micro (an IBM compatible) running an 8-MHz clock with a 8087 coprocessor can analyze data at least as fast as the minicomputers presently being used with the Adelaide PR rad ar and at a significantly lower cost. The processed winds data will be stored in nonvolatile CMOS RAM modules; about 0.5 to 1 Mbyte is required to store one week's information.

Persistence of pathogenic prion protein during simulated wastewater treatment processes

USGS Publications Warehouse

Hinckley, G.T.; Johnson, C.J.; Jacobson, K.H.; Bartholomay, C.; Mcmahon, K.D.; McKenzie, D.; Aiken, Judd M.; Pedersen, J.A.

2008-01-01

Transmissible spongiform encephalopathies (TSEs, prion diseases) are a class of fatal neurodegenerative diseases affecting a variety of mammalian species including humans. A misfolded form of the prion protein (PrP TSE) is the major, if not sole, component of the infectious agent. Prions are highly resistant to degradation and to many disinfection procedures suggesting that, if prions enter wastewater treatment systems through sewers and/or septic systems (e.g., from slaughterhouses, necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material, prions could survive conventional wastewater treatment Here, we report the results of experiments examining the partitioning and persistence of PrPTSE during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. Incubation with activated sludge did not result in significant PrPTSE degradation. PrPTSE and prion infectivity partitioned strongly to activated sludge solids and are expected to enter biosolids treatment processes. A large fraction of PrPTSE survived simulated mesophilic anaerobic sludge digestion. The small reduction in recoverable PrPTSE after 20-d anaerobic sludge digestion appeared attributable to a combination of declining extractability with time and microbial degradation. Our results suggest that if prions were to enter municipal wastewater treatment systems, most would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. ?? 2008 American Chemical Society.

[Public relations in institutions and establishments of the health administration system].

PubMed

Martynenko, A V

2002-01-01

The article is dedicated to development of directions and specific functions of the health system bodies/institutions public relations (PR) activities. Priorities are set forth depending on the form of property thereof. A complex use of approaches toward carrying out of PR activities permits optimizing work both within the system itself and relations with the society as a whole.

Knowledge of Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Men Who Have Sex with Men in Denver, Colorado

PubMed Central

Al-Tayyib, Alia A.; Thrun, Mark W.; Haukoos, Jason S.; Walls, N. Eugene

2014-01-01

As part of the National HIV Behavioral Surveillance System among men who have sex with men (MSM) in Denver, Colorado, we assessed knowledge of pre-exposure prophylaxis (PrEP); willingness to use PrEP; and potential changes in risk behaviors among HIV-negative participants reporting sexual activity with a male partner in the preceding 12 months. We examined knowledge of PrEP before (2008) and after (2011) results of the iPrEx trial were available. Of the 425 participants in the 2008 sample, 91 (21 %) were aware of PrEP compared to 131 (28 %) of the 461 participants in the 2011 sample (adjusted prevalence ratio: 1.43, 95 % confidence interval: 1.18, 1.72). Despite the increase in 2011, few MSM in Denver were aware of PrEP. Educating high-risk MSM about the potential utility of PrEP as an adjunct to other effective prevention methods is needed when considering the addition of PrEP to the HIV prevention arsenal. PMID:23824227

Differing Experiences with Pre-Exposure Prophylaxis in Boston Among Lesbian, Gay, Bisexual, and Transgender Specialists and Generalists in Primary Care: Implications for Scale-Up.

PubMed

Krakower, Douglas S; Ware, Norma C; Maloney, Kevin M; Wilson, Ira B; Wong, John B; Mayer, Kenneth H

2017-07-01

The Centers for Disease Control and Prevention estimates that one in four sexually active men who have sex with men (MSM) could decrease their HIV risk by using HIV pre-exposure prophylaxis (PrEP). Because many MSM access healthcare from primary care providers (PCPs), these clinicians could play an important role in providing access to PrEP. Semistructured qualitative interviews were conducted with 31 PCPs in Boston, MA, to explore how they approach decisions about prescribing PrEP to MSM and their experiences with PrEP provision. Purposive sampling included 12 PCPs from an urban community health center specializing in the care of lesbian, gay, bisexual, and transgender persons ("LGBT specialists") and 19 PCPs from a general academic medical center ("generalists"). Analyses utilized an inductive approach to identify emergent themes. Both groups of PCPs approached prescribing decisions about PrEP as a process of informed decision-making with patients. Providers would defer to patients' preferences if they were unsure about the appropriateness of PrEP. LGBT specialists and generalists were at vastly different stages of adopting PrEP into practice. For LGBT specialists, PrEP was a disruptive innovation that rapidly became normative in practice. Generalists had limited experience with PrEP; however, they desired succinct decision-support tools to help them achieve proficiency, because they considered preventive medicine to be central to their professional role. As generalists vastly outnumber LGBT specialists in the United States, interventions to support PrEP provision by generalists could accelerate the scale-up of PrEP for MSM nationally, which could in turn decrease HIV incidence for this priority population.

Production of cattle lacking prion protein

PubMed Central

Richt, Jürgen A; Kasinathan, Poothappillai; Hamir, Amir N; Castilla, Joaquin; Sathiyaseelan, Thillai; Vargas, Francisco; Sathiyaseelan, Janaki; Wu, Hua; Matsushita, Hiroaki; Koster, Julie; Kato, Shinichiro; Ishida, Isao; Soto, Claudio; Robl, James M; Kuroiwa, Yoshimi

2010-01-01

Prion diseases are caused by propagation of misfolded forms of the normal cellular prion protein PrPC, such as PrPBSE in bovine spongiform encephalopathy (BSE) in cattle and PrPCJD in Creutzfeldt-Jakob disease (CJD) in humans1. Disruption of PrPC expression in mice, a species that does not naturally contract prion diseases, results in no apparent developmental abnormalities2–5. However, the impact of ablating PrPC function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrPC-deficient cattle produced by a sequential gene-targeting system6. At over 20 months of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively normal. Brain tissue homogenates are resistant to prion propagation in vitro as assessed by protein misfolding cyclic amplification7. PrPC-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins. PMID:17195841

Introducing a Rigid Loop Structure from Deer into Mouse Prion Protein Increases Its Propensity for Misfolding In Vitro

PubMed Central

Kyle, Leah M.; John, Theodore R.; Schätzl, Hermann M.; Lewis, Randolph V.

2013-01-01

Prion diseases are fatal neurodegenerative disorders characterized by misfolding of the cellular prion protein (PrPc) into the disease-associated isoform (PrPSc) that has increased β-sheet content and partial resistance to proteolytic digestion. Prion diseases from different mammalian species have varying propensities for transmission upon exposure of an uninfected host to the infectious agent. Chronic Wasting Disease (CWD) is a highly transmissible prion disease that affects free ranging and farmed populations of cervids including deer, elk and moose, as well as other mammals in experimental settings. The molecular mechanisms allowing CWD to maintain comparatively high transmission rates have not been determined. Previous work has identified a unique structural feature in cervid PrP, a rigid loop between β-sheet 2 and α-helix 2 on the surface of the protein. This study was designed to test the hypothesis that the rigid loop has a direct influence on the misfolding process. The rigid loop was introduced into murine PrP as the result of two amino acid substitutions: S170N and N174T. Wild-type and rigid loop murine PrP were expressed in E. coli and purified. Misfolding propensity was compared for the two proteins using biochemical techniques and cell free misfolding and conversion systems. Murine PrP with a rigid loop misfolded in cell free systems with greater propensity than wild type murine PrP. In a lipid-based conversion assay, rigid loop PrP converted to a PK resistant, aggregated isoform at lower concentrations than wild-type PrP. Using both proteins as substrates in real time quaking-induced conversion, rigid loop PrP adopted a misfolded isoform more readily than wild type PrP. Taken together, these findings may help explain the high transmission rates observed for CWD within cervids. PMID:23825561

Binding of Single Walled Carbon Nanotube to WT and Mutant HIV-1 Proteases: Analysis of Flap Dynamics and Binding Mechanism

PubMed Central

Meher, Biswa Ranjan; Wang, Yixuan

2012-01-01

Most of the currently treated HIV-1 protease (HIV-PR) inhibitors have been prone to suffer from the mutations associated drug resistance. Therefore, it is necessary to search for potent alternatives against the drug resistance. In the current study we have tested the single-walled carbon nanotube (SWCNT) as an inhibitor in wild type (WT) as well as in three primary mutants (I50VPR, V82APR and I84VPR) of the HIV-1-PR through docking the SWCNT in the active site region, and then performed all-atom MD simulations for the complexes. The conformational dynamics of HIV-PR with a 20 ns trajectory reveals that the SWCNT can effectively bind to the HIV-1-PR active site and regulate the flap dynamics such as maintaining the flap-flap closed. To gain an insight into the binding affinity, we also performed the MM-PBSA based binding free energy calculations for the four HIV-PR/SWCNT complexes. It was observed that, although the binding between the SWCNT and the HIV-PR decreases due to the mutations, the SWCNTs bind to the HIV-PRs 3–5 folds stronger than the most potent HIV-1-PR inhibitor, TMC114. Remarkably, the significant interactions with binding energy higher than 1 kcal/mol focus on the flap and active regions, which favors closing flap-flap and deactivating the active residues of the HIV-PR. The flap dynamics and binding strength information for HIV-PR and SWCNTs can help design SWCNT-based HIV-1-PR inhibitors. PMID:23142620

Transgender Women in Clinical Trials of Pre-Exposure Prophylaxis

PubMed Central

Sevelius, Jae M.; Guanira, Juan V.; Aguilar, Jana Villayzan; Chariyalertsak, Suwat; Deutsch, Madeline B.

2016-01-01

Abstract: Lessons were learned with trans women who participated (as volunteers and investigators) in trials of HIV pre-exposure prophylaxis (PrEP). Trans women are not men. Compared with men who have sex with men, trans women trial participants were more likely to be involved with transactional sex, had more sexual partners, and were less likely to have PrEP medications detected in blood. Trans women define themselves differently in different cultures. One best practice is to ask at least 2 gender questions: sex assigned at birth and current gender. More information is needed to fully situate PrEP efficacy for trans women, including analysis of drug–drug interactions between PrEP medications and feminizing hormones and PrEP drug penetration into neovaginal tissues. Including trans women in studies is helpful only if their participation is specifically reported, as could occur in a table of baseline characteristics of the enrolled cohort. Gender-affirming care is important to foster appropriate uptake and use of PrEP. Such care includes use of preferred pronouns and names, safety to use the bathroom of choice, and access to gender-affirming hormone therapy and surgery. The consistent finding that PrEP works when taken across diverse populations having diverse practices related to gender, sexual intercourse, and hormone use provides a basis for offering PrEP to people at substantial risk of acquiring HIV although some subgroups may not have been fully represented in trials. Nonetheless, specific PrEP implementation science for trans women (and men) is essential to develop best practices for PrEP delivery and use. PMID:27429187

Transgender Women in Clinical Trials of Pre-Exposure Prophylaxis.

PubMed

Grant, Robert M; Sevelius, Jae M; Guanira, Juan V; Aguilar, Jana Villayzan; Chariyalertsak, Suwat; Deutsch, Madeline B

2016-08-15

Lessons were learned with trans women who participated (as volunteers and investigators) in trials of HIV pre-exposure prophylaxis (PrEP). Trans women are not men. Compared with men who have sex with men, trans women trial participants were more likely to be involved with transactional sex, had more sexual partners, and were less likely to have PrEP medications detected in blood. Trans women define themselves differently in different cultures. One best practice is to ask at least 2 gender questions: sex assigned at birth and current gender. More information is needed to fully situate PrEP efficacy for trans women, including analysis of drug-drug interactions between PrEP medications and feminizing hormones and PrEP drug penetration into neovaginal tissues. Including trans women in studies is helpful only if their participation is specifically reported, as could occur in a table of baseline characteristics of the enrolled cohort. Gender-affirming care is important to foster appropriate uptake and use of PrEP. Such care includes use of preferred pronouns and names, safety to use the bathroom of choice, and access to gender-affirming hormone therapy and surgery. The consistent finding that PrEP works when taken across diverse populations having diverse practices related to gender, sexual intercourse, and hormone use provides a basis for offering PrEP to people at substantial risk of acquiring HIV although some subgroups may not have been fully represented in trials. Nonetheless, specific PrEP implementation science for trans women (and men) is essential to develop best practices for PrEP delivery and use.

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice

PubMed Central

Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1–4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain. PMID:29220360

Rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of the novel anticancer agent PR-104 and its major metabolites in human plasma: Application to a pharmacokinetic study.

PubMed

Gu, Yongchuan; Wilson, William R

2009-10-01

PR-104 is a dinitrobenzamide mustard currently in clinical trial as a hypoxia-activated prodrug. It is converted systemically to the corresponding alcohol, PR-104A, which is activated by nitroreduction to the hydroxylamine (PR-104H) and amine (PR-104M). PR-104A is also metabolised to the O-glucuronide (PR-104G), and by oxidative debromoethylation to the semi-mustard PR-104S. We now report a validated ultra-high-pressure liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) method for the determination of these metabolites in human plasma. Plasma proteins were precipitated with acidified methanol and the supernatant diluted into water. Aliquots were analysed by UHPLC-MS/MS using a Zorbax Eclipse XDB-C18 Rapid Resolution HT (50mmx2.1mm, 1.8microm) column and gradient of acetonitrile and 0.01% formic acid with a 6min run time. The method had a linear range of 0.1-50microM for PR-104, PR-104A and PR-104G, 0.05-5microM for PR-104H, 0.025-2.5microM for PR-104M and 0.01-1microM for PR-104S. The intra-day and inter-day precision and accuracy were within 14%. The extraction recovery of all analytes was over 87%. The validated method was illustrated by using it to study the pharmacokinetics of PR-104 and its metabolites in a human patient.

Community-Based Surveillance to Monitor Mortality in a Malaria-Endemic and Ebola-Epidemic Setting in Rural Guinea.

PubMed

Tiffany, Amanda; Moundekeno, Faya Pascal; Traoré, Alexis; Haile, Melat; Sterk, Esther; Guilavogui, Timothé; Serafini, Micaela; Genton, Blaise; Grais, Rebecca F

2016-12-07

Multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. Community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. We retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (Koundou) in Guinea. Deaths were recorded by key informants and classified as due to malaria or another cause. Malaria deaths were those reported as due to malaria or fever in the 3 days before death with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those due to select symptoms in the EVD case definition. Deaths were aggregated by sous-préfecture and analyzed by a 6-month period. A total of 43,000 individuals were monitored by the surveillance system; 1,242 deaths were reported from July 2011-June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria-attributable proportional mortality decreased by 26.5% (95% confidence interval [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3-30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were reported from November 2013 to March 2014 including the first two laboratory-confirmed EVD deaths. Community surveillance can capture information on mortality in areas where data collection is weak, but determining causes of death remains challenging. It can also be useful for outbreak detection if timeliness of data collection and reporting facilitate real-time data analysis. © The American Society of Tropical Medicine and Hygiene.

Preparation and physical properties of the GdPr-123 system

NASA Astrophysics Data System (ADS)

Yamani, Z.; Akhavan, M.

1997-06-01

The Gd - Pr solid solution of the `123' crystal structure, 0953-2048/10/6/008/img1 (GdPr-123) with 0953-2048/10/6/008/img2 has been prepared by the standard solid-state reaction technique. Details of sample preparation and results of XRD, SEM, TGA, DT, 0953-2048/10/6/008/img3, and 0953-2048/10/6/008/img4 measurements are reported. For 0953-2048/10/6/008/img5, GdPr-123 is non-superconducting down to 10 K and does not show `metallic' conduction. Samples have a predominantly single-phase orthorhombic structure with Pmmm symmetry and a small percentage (0953-2048/10/6/008/img6) of the Ba sites are occupied by Pr ions in some Pr-rich samples. The lower critical field value measured lies in the range of 10 mT. The nominal valence of the Cu ion in the whole range of x is determined; at the metal - semiconductor boundary 0953-2048/10/6/008/img7, which is smaller by only 0.18 than the value 2.33 of the fully oxygenated 0953-2048/10/6/008/img8 (Gd-123) system. However, the valence of Pr is 3.86+. We suggest that the increasing band filling and localization of states due to the disorder effects together with Pr doping could cause the observed metal - semiconducting transition; qualitatively this is the same as the oxygen depletion case.

Non-local boxes and their implementation in Minecraft

NASA Astrophysics Data System (ADS)

Simnacher, Timo Yannick

PR-boxes are binary devices connecting two remote parties satisfying x AND y = a + b mod 2, where x and y denote the binary inputs and a and b are the respective outcomes without signaling. These devices are named after their inventors Sandu Popescu and Daniel Rohrlich and saturate the Clauser-Horne-Shimony-Holt (CHSH) inequality. This Bell-like inequality bounds the correlation that can exist between two remote, non-signaling, classical systems described by local hidden variable theories. Experiments have now convincingly shown that quantum entanglement cannot be explained by local hidden variable theories. Furthermore, the CHSH inequality provides a method to distinguish quantum systems from super-quantum correlations. The correlation between the outputs of the PR-box goes beyond any quantum entanglement. Though PR-boxes would have impressive consequences, as far as we know they are not physically realizable. However, by introducing PR-boxes to Minecraft as part of the redstone system, which simulates the electrical components for binary computing, we can experience the consequences of super-quantum correlations. For instance, Wim van Dam proved that two parties can use a sufficient number of PR-boxes to compute any Boolean function f(x,y) with only one bit of communication.

Multiple drug resistant mechanisms against darunavir, amprenavir, and nelfinavir of HIV-1 PR

NASA Astrophysics Data System (ADS)

Liu, Xiaoqing; Dai, Qi; Xiu, Zhilong

2013-02-01

Acquired immune deficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV), which is infecting more humans and is expanding faster in the world. The illness interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people with working immune systems. HIV-1 PR is one of the major targets of anti-AIDS drug discovery. It is, therefore, necessary to develop some inhibitors against HIV-1 PR. In this work, we executed molecular dynamics (MDs) simulation of HIV-1 PR with drugs darunavir (DRV), amprenavir (APV), nelfinavir (NFV), and examined the resistant mechanism of L10I, G48V, I54V, and L90M mutations of this PR, aiming at designing promising drugs. The comparative analysis suggests that the existences of dodecahydroisoquinoline ring at P1' subsite, 4-aminophenylsulfonamide at P2' subsite, and bis-tetrahydrofuranylurethane at P2 subsite are helpful for maintaining the high affinity of the inhibitor for the protease and exhibiting high potency against multiple drug resistance (MDR) mutant protease.

Amphoteric doping of praseodymium Pr 3+ in SrTiO 3 grain boundaries

DOE PAGES

Yang, H.; Lee, H. S.; Kotula, P. G.; ...

2015-03-26

Charge Compensation in rare-earth Praseodymium (Pr 3+) doped SrTiO 3 plays an important role in determining the overall photoluminescence properties of the system. Here, the Pr 3+ doping behavior in SrTiO 3 grain boundaries (GBs) is analyzed using aberration corrected scanning transmission electron microscopy (STEM). The presence of Pr 3+ induces structure variations and changes the statistical prevalence of GB structures. In contrast to the assumption that Pr 3+ substitutes for A site as expected in the bulk, Pr 3+ is found to substitute both Sr and Ti sites inside GBs with the highest concentration in the Ti sites. Asmore » a result, this amphoteric doping behavior in the boundary plane is further confirmed by first principles theoretical calculations.« less

Amphoteric Doping of Praseodymium Pr3+ in SrTiO3 Grain Boundaries

DOE PAGES

Yang, Hao; Lee, H. S.; Kotula, Paul G.; ...

2015-03-23

Charge Compensation in rare-earth Praseodymium (Pr 3+) doped SrTiO 3 plays an important role in determining the overall photoluminescence properties of the system. Here, the Pr 3+ doping behavior in SrTiO 3 grain boundaries (GBs) is analyzed using aberration corrected scanning transmission electron microscopy (STEM). The presence of Pr 3+ induces structure variations and changes the statistical prevalence of GB structures. In contrast to the assumption that Pr 3+ substitutes for A site as expected in the bulk, Pr 3+ is found to substitute both Sr and Ti sites inside GBs with the highest concentration in the Ti sites. Asmore » a result, this amphoteric doping behavior in the boundary plane is further confirmed by first principles theoretical calculations.« less

Who Will Use Pre-Exposure Prophylaxis (PrEP) and Why?: Understanding PrEP Awareness and Acceptability amongst Men Who Have Sex with Men in the UK--A Mixed Methods Study.

PubMed

Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa

2016-01-01

Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18-25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities.

Who Will Use Pre-Exposure Prophylaxis (PrEP) and Why?: Understanding PrEP Awareness and Acceptability amongst Men Who Have Sex with Men in the UK – A Mixed Methods Study

PubMed Central

Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa

2016-01-01

Background Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Methods Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Results Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18–25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. Conclusion These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities. PMID:27093430

Generating Bona Fide Mammalian Prions with Internal Deletions.

PubMed

Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel

2016-08-01

Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative disorders. Other aggregation-prone proteins appear to have a prion-like mode of expansion in brains, such as in Alzheimer's or Parkinson's diseases. To date, the resolution of prion structure remains elusive. Thus, to genetically define the landscape of regions critical for prion conversion, we tested the effect of short deletions. We found that, surprisingly, removal of a portion of PrP, the C terminus of alpha-helix H2, did not hamper prion formation but generated infectious agents with an internal deletion that showed characteristics essentially similar to those of original infecting strains. Thus, we demonstrate that completeness of the residues inside prions is not necessary for maintaining infectivity and the main strain-specific information, while reporting one of the few if not the only bona fide prions with an internal deletion. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Generating Bona Fide Mammalian Prions with Internal Deletions

PubMed Central

Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human

2016-01-01

ABSTRACT Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. IMPORTANCE Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative disorders. Other aggregation-prone proteins appear to have a prion-like mode of expansion in brains, such as in Alzheimer's or Parkinson's diseases. To date, the resolution of prion structure remains elusive. Thus, to genetically define the landscape of regions critical for prion conversion, we tested the effect of short deletions. We found that, surprisingly, removal of a portion of PrP, the C terminus of alpha-helix H2, did not hamper prion formation but generated infectious agents with an internal deletion that showed characteristics essentially similar to those of original infecting strains. Thus, we demonstrate that completeness of the residues inside prions is not necessary for maintaining infectivity and the main strain-specific information, while reporting one of the few if not the only bona fide prions with an internal deletion. PMID:27226369

Benefits of Pulmonary Rehabilitation in Idiopathic Pulmonary Fibrosis

PubMed Central

Swigris, Jeffrey J.; Fairclough, Diane L.; Morrison, Marianne; Make, Barry; Kozora, Elizabeth; Brown, Kevin K.; Wamboldt, Frederick S.

2013-01-01

BACKGROUND Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR’s effects on certain important outcomes is lacking. METHODS We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. RESULTS Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. CONCLUSIONS PR improves functional capacity and fatigue in patients with IPF. (ClinicalTrials.gov registration NCT00692796.) PMID:21333082

Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation.

PubMed

Ross, Ian; Mejia, Carlos; Melendez, Johanna; Chan, Philip A; Nunn, Amy C; Powderly, William; Goodenberger, Katherine; Liu, Jingxia; Mayer, Kenneth H; Patel, Rupa R

2017-01-01

HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

From modeling to morals: imagining the future of HIV PREP in Lesotho.

PubMed

Kenworthy, Nora J; Bulled, Nicola

2013-08-01

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV-based pre-exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at-risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother-to-child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive measures. In this sense, it represents a new bio-technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries' struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource-poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections. © 2013 John Wiley & Sons Ltd.

New insights into flavivirus biology: the influence of pH over interactions between prM and E proteins

NASA Astrophysics Data System (ADS)

Oliveira, Edson R. A.; de Alencastro, Ricardo B.; Horta, Bruno A. C.

2017-11-01

Diseases caused by flaviviruses, such as dengue and zika, are globally recognized as major threats. During infection, a critical point in their replicative cycle is the maturation step, which occurs throughout the cellular exocytic pathway. This step is a pH-dependent process that involves the modification of the viral envelope by converting prM (pre-membrane) into M (membrane) proteins with the release of a "pr peptide". After this reaction, the pr peptides remain bound to the viral envelope while the virions cross the acidic trans-Golgi network, and are released only at neutral pH after secretion of the virus particles. Despite this current knowledge, the molecular basis of the flavivirus maturation step is largely unknown. Here, based on the crystal structure of the dengue pr-E complex ("pr peptide" bound to virus envelope protein) and using molecular dynamics simulations, we found that the pH shift from acidic to neutral yields considerable structural changes in the system. Dynamic cross correlation maps and root mean square deviation analyses revealed that the pr-E junction is clearly unstable under neutral pH. Secondary structure analysis also revealed that the fusion loop region, present in the E protein, is sensitive to pH and tends to unstructure at a neutral environment. Moreover, we found that five residues present in the E protein, Gly102, His244, Thr70, Thr68 and Asn67 are critical to confer stability to the pr-E complex while inside the Golgi apparatus. This work brings details about the dynamical behavior of the pr-E system, helps to better understand the flavivirus biology and may also be of use in the development of novel antiviral strategies.

76 FR 25618 - Proposed Processed Raspberry Promotion, Research, and Information Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

...; FV-07-705-PR-2B] RIN 0581-AC79 Proposed Processed Raspberry Promotion, Research, and Information... industry-funded promotion, research, and information program for processed raspberries. The proposed program, Processed Raspberry Promotion, Research, and Information Order (Proposed Order), was submitted to...

Comparative adoption of cone beam computed tomography and panoramic radiography machines across Australia.

PubMed

Zhang, A; Critchley, S; Monsour, P A

2016-12-01

The aim of the present study was to assess the current adoption of cone beam computed tomography (CBCT) and panoramic radiography (PR) machines across Australia. Information regarding registered CBCT and PR machines was obtained from radiation regulators across Australia. The number of X-ray machines was correlated with the population size, the number of dentists, and the gross state product (GSP) per capita, to determine the best fitting regression model(s). In 2014, there were 232 CBCT and 1681 PR machines registered in Australia. Based on absolute counts, Queensland had the largest number of CBCT and PR machines whereas the Northern Territory had the smallest number. However, when based on accessibility in terms of the population size and the number of dentists, the Australian Capital Territory had the most CBCT machines and Western Australia had the most PR machines. The number of X-ray machines correlated strongly with both the population size and the number of dentists, but not with the GSP per capita. In 2014, the ratio of PR to CBCT machines was approximately 7:1. Projected increases in either the population size or the number of dentists could positively impact on the adoption of PR and CBCT machines in Australia. © 2016 Australian Dental Association.

Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles for active targeting of breast cancer cells.

PubMed

Kouchakzadeh, Hasan; Shojaosadati, Seyed Abbas; Mohammadnejad, Javad; Paknejad, Malihe; Rasaee, Mohammad Javad

2012-01-01

With PR81 as a murine monoclonal antibody (mAb) that was prepared against the human breast cancer, the MUC1 receptor specific targeting is possible. In this study, PR81-conjugated bovine serum albumin (BSA) nanoparticles loaded with anticancer drug 5-fluorouracil (5-FU) were developed. Enzyme linked immunosorbant assay (ELISA) results showed high immunoreactivity of PR81 mAb conjugated to nanoparticles towards MUC1 related peptide or native cancerous MUC1 and almost no cross-reaction to non-specific proteins. In vitro experiments were performed to determine the ability of this new drug delivery system on overcoming MCF-7 breast cancer cells in comparison with four other systems. The results revealed that these cell-type specific drug loaded nanoparticles could achieve more cell death as compared to when the 5-FU was used with no carriers. Stability studies of produced drug delivery system proved high immunoreactivity of conjugated PR81 even after 11 days of storage in room temperature.

The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies

PubMed Central

Gomez, Gabriela B.; Borquez, Annick; Case, Kelsey K.; Wheelock, Ana; Vassall, Anna; Hankins, Catherine

2013-01-01

Background Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions. Methods and Findings We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP. Conclusions Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary PMID:23554579

Understanding influences on the uptake of pulmonary rehabilitation in the East of England: an Inclusive Design/mixed-methods study protocol.

PubMed

Liu, Yuanyuan; Dickerson, Terry; Early, Frances; Fuld, Jonathan; Clarkson, P John

2018-04-24

1.2 million people in the UK have chronic obstructive pulmonary disease (COPD) that causes breathlessness, difficulty with daily activities, infections and hospitalisation. Pulmonary rehabilitation (PR), a programme of supervised exercise and education, is recommended for patients with COPD. However, only 1 in 10 of those who need it receive PR. Also, the UK National COPD Audit Programme concluded that the COPD treatment might not be accessible to people with disabilities. This paper applies an Inclusive Design approach to community-based PR service provisions. It aims to inform improvements to the PR service by identifying barriers to the uptake of PR in the COPD care journey in relation to patients' capabilities that can affect their access to PR. The protocol includes four steps. Step 1 will involve interviews with healthcare professionals and patients to gather insight into their experiences and produce a hierarchical task analysis of the COPD care journeys. Step 2 will estimate the service exclusion: the demand of every task on patients' capabilities will be rated by predefined scales, and the proportion of the population excluded from the service will be estimated by an exclusion calculator. Step 3 will identify the challenges of the PR service; a framework analysis will guide the data analysis of the interviews and care journey. Step 4 will propose recommendations to help patients manage their COPD care informed by the challenges identified in step 3 and refine recommendations through interviews and focus groups. The Cambridge Central Research Ethics Committee gave the study protocol a positive ethical opinion (17/EE/0136). Study results will be disseminated through peer-reviewed journals, conferences and the British Lung Foundation networks. They will also be fed into a Research for Patient Benefit project on increasing the referral and uptake of PR. © 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.

Bayesian geostatistical modelling of soil-transmitted helminth survey data in the People's Republic of China.

PubMed

Lai, Ying-Si; Zhou, Xiao-Nong; Utzinger, Jürg; Vounatsou, Penelope

2013-12-18

Soil-transmitted helminth infections affect tens of millions of individuals in the People's Republic of China (P.R. China). There is a need for high-resolution estimates of at-risk areas and number of people infected to enhance spatial targeting of control interventions. However, such information is not yet available for P.R. China. A geo-referenced database compiling surveys pertaining to soil-transmitted helminthiasis, carried out from 2000 onwards in P.R. China, was established. Bayesian geostatistical models relating the observed survey data with potential climatic, environmental and socioeconomic predictors were developed and used to predict at-risk areas at high spatial resolution. Predictors were extracted from remote sensing and other readily accessible open-source databases. Advanced Bayesian variable selection methods were employed to develop a parsimonious model. Our results indicate that the prevalence of soil-transmitted helminth infections in P.R. China considerably decreased from 2005 onwards. Yet, some 144 million people were estimated to be infected in 2010. High prevalence (>20%) of the roundworm Ascaris lumbricoides infection was predicted for large areas of Guizhou province, the southern part of Hubei and Sichuan provinces, while the northern part and the south-eastern coastal-line areas of P.R. China had low prevalence (<5%). High infection prevalence (>20%) with hookworm was found in Hainan, the eastern part of Sichuan and the southern part of Yunnan provinces. High infection prevalence (>20%) with the whipworm Trichuris trichiura was found in a few small areas of south P.R. China. Very low prevalence (<0.1%) of hookworm and whipworm infections were predicted for the northern parts of P.R. China. We present the first model-based estimates for soil-transmitted helminth infections throughout P.R. China at high spatial resolution. Our prediction maps provide useful information for the spatial targeting of soil-transmitted helminthiasis control interventions and for long-term monitoring and surveillance in the frame of enhanced efforts to control and eliminate the public health burden of these parasitic worm infections.

Bayesian geostatistical modelling of soil-transmitted helminth survey data in the People’s Republic of China

PubMed Central

2013-01-01

Background Soil-transmitted helminth infections affect tens of millions of individuals in the People’s Republic of China (P.R. China). There is a need for high-resolution estimates of at-risk areas and number of people infected to enhance spatial targeting of control interventions. However, such information is not yet available for P.R. China. Methods A geo-referenced database compiling surveys pertaining to soil-transmitted helminthiasis, carried out from 2000 onwards in P.R. China, was established. Bayesian geostatistical models relating the observed survey data with potential climatic, environmental and socioeconomic predictors were developed and used to predict at-risk areas at high spatial resolution. Predictors were extracted from remote sensing and other readily accessible open-source databases. Advanced Bayesian variable selection methods were employed to develop a parsimonious model. Results Our results indicate that the prevalence of soil-transmitted helminth infections in P.R. China considerably decreased from 2005 onwards. Yet, some 144 million people were estimated to be infected in 2010. High prevalence (>20%) of the roundworm Ascaris lumbricoides infection was predicted for large areas of Guizhou province, the southern part of Hubei and Sichuan provinces, while the northern part and the south-eastern coastal-line areas of P.R. China had low prevalence (<5%). High infection prevalence (>20%) with hookworm was found in Hainan, the eastern part of Sichuan and the southern part of Yunnan provinces. High infection prevalence (>20%) with the whipworm Trichuris trichiura was found in a few small areas of south P.R. China. Very low prevalence (<0.1%) of hookworm and whipworm infections were predicted for the northern parts of P.R. China. Conclusions We present the first model-based estimates for soil-transmitted helminth infections throughout P.R. China at high spatial resolution. Our prediction maps provide useful information for the spatial targeting of soil-transmitted helminthiasis control interventions and for long-term monitoring and surveillance in the frame of enhanced efforts to control and eliminate the public health burden of these parasitic worm infections. PMID:24350825

The cost and impact of scaling up pre-exposure prophylaxis for HIV prevention: a systematic review of cost-effectiveness modelling studies.

PubMed

Gomez, Gabriela B; Borquez, Annick; Case, Kelsey K; Wheelock, Ana; Vassall, Anna; Hankins, Catherine

2013-01-01

Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions. We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP. Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention--cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary.

Perceived HIV risk, actual sexual HIV risk and willingness to take pre-exposure prophylaxis among men who have sex with men in Toronto, Canada.

PubMed

Kesler, Maya A; Kaul, Rupert; Myers, Ted; Liu, Juan; Loutfy, Mona; Remis, Robert S; Gesink, Dionne

2016-11-01

Pre-exposure prophylaxis (PrEP) reduces HIV acquisition. Our goal was to determine the willingness of men who have sex with men (MSM) to take PrEP given perceived and actual HIV risk. HIV-negative MSM were recruited from September 2010 to June 2012 and asked about PrEP willingness and perceived HIV risk. Actual sexual HIV risk was measured by three condom-use components generated through principal components analysis. General HIV risk was measured using the HIV Incidence Risk Index for MSM (HIRI-MSM). Model 1 measured PrEP willingness given perceived and actual sexual HIV risk. Model 2 included actual HIV sexual risk, perceived HIV risk and general HIV risk. Model 3 removed actual sexual HIV risk. We recruited 150 HIV-negative MSM. About 55% were willing to take PrEP. Reasons for PrEP unwillingness were: low perceived risk (64%), side-effect concerns (44%), daily pill burden (16%) and efficacy concerns (4%). Model 1: MSM with high compared to low actual sexual HIV risk were more willing to use PrEP (OR 27.11, 95% CI 1.33-554.43) after adjusting for perceived risk, which was not significantly associated with PrEP willingness (OR 4.79, 95% CI 0.72-31.96). Model 2: MSM with high compared to low actual sexual HIV risk were more willing to use PrEP (OR 29.85, 95% CI 1.39-640.53) after adjusting for perceived and general HIV risk, neither of which was significantly associated with PrEP willingness (OR 5.07, 95% CI 0.73-35.09) and (OR 1.58, 95% CI 0.37-6.79), respectively. Model 3: After removing actual sexual HIV risk, MSM with high compared to low perceived risk were more willing to use PrEP (OR 6.85, 95% CI 1.23-38.05), and the HIRI-MSM general risk index was not associated with PrEP willingness (OR 1.87, 95% CI 0.54-6.54). Therefore, actual sexual HIV risk was the best predictor of PrEP willingness and general HIV risk did not inform PrEP willingness.

African American men's understanding and perceptions about prostate cancer: why multiple dimensions of health literacy are important in cancer communication.

PubMed

Friedman, Daniela B; Corwin, Sara J; Dominick, Gregory M; Rose, India D

2009-10-01

Prostate cancer (PrCA) is the most diagnosed cancer among men in the United States, especially among African American (AA) men. The purpose of this formative study was to explore the implications of applying Nutbeam's multidimensional health literacy framework to AA men's understanding of PrCA information. Participants were 25 AA men aged 45 and older in South Carolina. Their functional health literacy was assessed using two modified Cloze tests and the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA). Men also participated in interviews or focus groups during which they were asked questions about PrCA risk, prevention, and screening. Transcripts were reviewed for recurrent themes and analyzed qualitatively using NVivo7. Mean S-TOFHLA was 28.28 (+/-1.98), implying "adequate" comprehension. Mean Cloze was .71 (+/-.05) for a Grade 8 document and .66 (+/-.04) for a Grade 13 document, also showing "adequate" comprehension. Cloze scores for the Grade 8 resource were lower for participants with less education (P = .047). Despite having satisfactory literacy test scores, results from interviews and focus groups revealed participants' limited understanding and misconceptions about PrCA risk. Many wanted information about screening and family history delivered word-of-mouth by AA women and church pastors as few of them had ever received or actively sought out PrCA resources. Using Nutbeam's framework, gaps in health literacy which were not adequately captured by the validated tools emerged during the interviews and focus groups. Study findings provide important implications for PrCA communication with AA men to correct misperceptions about cancer risk and motivate preventive behaviors.

[Mass media influence and risk of developing eating disorders in female students from Lima, Peru].

PubMed

Lazo Montoya, Yessenia; Quenaya, Alejandra; Mayta-Tristán, Percy

2015-12-01

Eating disorders (EDs) are a public health problem, and their relationship to mass media is still controversial. To assess whether there is an association between models of body image shown in mass media and the risk of developing EDs among female adolescent students from Lima, Peru. Cross-sectional study conducted in three schools located in the district of La Victoria, Lima, Peru. The risk of developing EDs was measured using the Eating Attitudes Test-26 (EAT-26), while mass media influence was measured using the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3), which was categorized into tertiles both in the overall score and its subscales (information, pressure, general internalization, and athletic internalization). Adjusted prevalence ratios (aPR) for EDs were estimated. Four hundred and eighty-three students were included, their median age was 14 ? 3 years old. A risk of developing an ED was observed in 13.9% of them. Students who are more influenced by mass media (upper tertile of the SATAQ-3) have a higher probability of having a risk of developing an ED (aPR: 4.24; 95% confidence interval |-CI-|: 2.10-8.56), as well as those who have a greater access to information (PR: 1.89; 95% CI: 1.09-3.25), suffer more pressure (PR: 4.97; 95% CI: 2.31-10.69), show a greater general internalization (PR: 5.00; 95% CI: 2.39-10.43), and show a greater level of athletic internalization (PR: 4.35; 95% CI: 2.19-8-66). The greater the influence of mass media, the greater the probability of having a risk of developing an ED among female students from Lima, Peru.

Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets

PubMed Central

Ganley, Robert P.; Iwagaki, Noboru; del Rio, Patricia; Baseer, Najma; Dickie, Allen C.; Boyle, Kieran A.; Polgár, Erika; Watanabe, Masahiko; Abraira, Victoria E; Zimmerman, Amanda

2015-01-01

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to “unclassified” cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn. PMID:25972186

Anatomy, taphonomy, and phylogenetic implications of a new specimen of Eolambia caroljonesa (Dinosauria: Ornithopoda) from the Cedar Mountain Formation, Utah, USA

PubMed Central

McDonald, Andrew T.; Gates, Terry A.; Zanno, Lindsay E.; Makovicky, Peter J.

2017-01-01

Background Eolambia caroljonesa is the most abundant dinosaur in the lower Cenomanian Mussentuchit Member of the Cedar Mountain Formation of Utah, and one of the most completely known non-hadrosaurid iguanodontians from North America. In addition to the large holotype and paratype partial skulls, copious remains of skeletally immature individuals, including three bonebeds, have been referred to E. caroljonesa. Nevertheless, aspects of the postcranial anatomy of this taxon, particularly the pelvic girdle, have remained ambiguous due to the lack of associated postcranial material of larger, more mature individuals. Methodology/Principal findings Here we describe a recently discovered associated partial postcranial skeleton of a large Eolambia caroljonesa. This specimen, FMNH PR 3847, provides new anatomical data regarding the vertebral column and pelvic girdle, supplementing previous diagnoses and descriptions of E. caroljonesa. A new phylogenetic analysis incorporating information from FMNH PR 3847 places E. caroljonesa as a basal hadrosauromorph closely related to Protohadros byrdi from the Cenomanian Woodbine Formation of Texas. Histological analysis of FMNH PR 3847 reveals that it represents a subadult individual eight to nine years of age. Taphonomic analysis indicates that FMNH PR 3847 was preserved in a crevasse splay deposit, along with an unusual abundance of small crocodylomorph material. Conclusions/Significance FMNH PR 3847 provides a wealth of new morphological data, adding to the anatomical and systematic characterization of Eolambia caroljonesa, and histological data, revealing new information on growth history in a basal hadrosauromorph. Taphonomic characterization of FMNH PR 3847 and associated vertebrate material will allow comparison with other vertebrate localities in the Mussentuchit Member of the Cedar Mountain Formation. PMID:28489871

LuAG:Pr3+-porphyrin based nanohybrid system for singlet oxygen production: Toward the next generation of PDTX drugs.

PubMed

Popovich, Kseniya; Tomanová, Kateřina; Čuba, Václav; Procházková, Lenka; Pelikánová, Iveta Terezie; Jakubec, Ivo; Mihóková, Eva; Nikl, Martin

2018-02-01

A highly prospective drug for the X-ray induced photodynamic therapy (PDTX), LuAG:Pr 3+ @SiO 2 -PpIX nanocomposite, was successfully prepared by a three step process: photo-induced precipitation of the Lu 3 Al 5 O 12 :Pr 3+ (LuAG:Pr 3+ ) core, sol-gel technique for amorphous silica coating, and a biofunctionalization by attaching the protoporphyrin IX (PpIX) molecules. The synthesis procedure provides three-layer nanocomposite with uniform shells covering an intensely luminescent core. Room temperature radioluminescence (RT RL) spectra as well as photoluminescence (RT PL) steady-state and time resolved spectra of the material confirm the non-radiative energy transfer from the core Pr 3+ ions to the PpIX outer layer. First, excitation of Pr 3+ ions results in the red luminescence of PpIX. Second, the decay measurements exhibit clear evidence of mentioned non-radiative energy transfer (ET). The singlet oxygen generation in the system was demonstrated by the 3'-(p-aminophenyl) fluorescein (APF) chemical probe sensitive to the singlet oxygen presence. The RT PL spectra of an X-ray irradiated material with the APF probe manifest the formation of singlet oxygen due to which enhanced luminescence around 530 nm is observed. Quenching studies, using NaN 3 as an 1 O 2 inhibitor, also confirm the presence of 1 O 2 in the system and rule out the parasitic reaction with OH radicals. To summarize, presented features of LuAG:Pr 3+ @SiO 2 -PpIX nanocomposite indicate its considerable potential for PDTX application. Copyright © 2018 Elsevier B.V. All rights reserved.

Mid-infrared emissions of Pr{sup 3+}-doped GeS{sub 2}–Ga{sub 2}S{sub 3}–CdI{sub 2} chalcohalide glasses

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

Lu, Chunfeng; Guo, Haitao, E-mail: guoht_001@opt.ac.cn; Xu, Yantao

2014-12-15

Graphical abstract: ∼4.6 μm mid-infrared fluorescence emission from Pr{sup 3+} in the sulfide glass is successfully observed at room temperature excited by a 2.01 μm Tm{sup 3+}:YAG ceramic laser system. - Highlights: • Serial Pr{sup 3+}-doped GeS{sub 2}–Ga{sub 2}S{sub 3}–CdI{sub 2} chalcohalide glasses were synthesized. • ∼4.6 μm mid-infrared fluorescence from Pr{sup 3+} was observed at room temperature. • The compositional dependence of luminescence properties was studied. • Radiative properties have been determined using the Judd–Ofelt theory. - Abstract: For elucidation of the glass composition’s influence on the spectroscopic properties in the chalcohalide system and the discovery of a newmore » material for applications in mid-infrared fiber-lasers, a serial Pr{sup 3+}-doped (100 − x)(0.8GeS{sub 2}·0.2Ga{sub 2}S{sub 3})xCdI{sub 2} (x = 5, 10, 15 and 20) chalcohalide glasses were prepared. ∼4.6 μm mid-infrared fluorescence emission from Pr{sup 3+} in the sulfide glass is successfully observed at room temperature excited by a 2.01 μm Tm{sup 3+}:YAG ceramic laser system, and the effective line-width of fluorescence band is 106–227 nm. Intense compositional dependence of mid-infrared emissions is found. The radiative rates of Pr{sup 3+} ions in these glasses were calculated by using the Judd–Ofelt theory.« less

Quantitative estimation of Tropical Rainfall Mapping Mission precipitation radar signals from ground-based polarimetric radar observations

NASA Astrophysics Data System (ADS)

Bolen, Steven M.; Chandrasekar, V.

2003-06-01

The Tropical Rainfall Mapping Mission (TRMM) is the first mission dedicated to measuring rainfall from space using radar. The precipitation radar (PR) is one of several instruments aboard the TRMM satellite that is operating in a nearly circular orbit with nominal altitude of 350 km, inclination of 35°, and period of 91.5 min. The PR is a single-frequency Ku-band instrument that is designed to yield information about the vertical storm structure so as to gain insight into the intensity and distribution of rainfall. Attenuation effects on PR measurements, however, can be significant and as high as 10-15 dB. This can seriously impair the accuracy of rain rate retrieval algorithms derived from PR signal returns. Quantitative estimation of PR attenuation is made along the PR beam via ground-based polarimetric observations to validate attenuation correction procedures used by the PR. The reflectivity (Zh) at horizontal polarization and specific differential phase (Kdp) are found along the beam from S-band ground radar measurements, and theoretical modeling is used to determine the expected specific attenuation (k) along the space-Earth path at Ku-band frequency from these measurements. A theoretical k-Kdp relationship is determined for rain when Kdp ≥ 0.5°/km, and a power law relationship, k = a Zhb, is determined for light rain and other types of hydrometers encountered along the path. After alignment and resolution volume matching is made between ground and PR measurements, the two-way path-integrated attenuation (PIA) is calculated along the PR propagation path by integrating the specific attenuation along the path. The PR reflectivity derived after removing the PIA is also compared against ground radar observations.

Healthcare Provider Contact and Pre-exposure Prophylaxis in Baltimore Men Who Have Sex With Men

PubMed Central

Raifman, Julia R.G.; Flynn, Colin; German, Danielle

2018-01-01

Introduction Pre-exposure prophylaxis (PrEP) safely and effectively prevents HIV in populations at high risk, including men who have sex with men (MSM). PrEP scale-up depends upon primary care providers and community-based organizations (CBOs) sharing PrEP information. This study aimed to determine whether healthcare provider or CBO contact was associated with PrEP awareness among Baltimore MSM. Methods This study used 2014 Baltimore MSM National HIV Behavioral Surveillance data, which included data on health care, HIV and sexually transmitted infection testing, and receipt of condoms from CBOs. In 2015, associations were estimated between healthcare contacts and PrEP awareness through logistic regression models controlling for age, race, and education and clustering by venue. Comparative analyses were conducted with HIV testing as outcome. Results There were 401 HIV-negative participants, of whom 168 (42%) were aware of PrEP. Visiting a healthcare provider in the past 12 months, receiving an HIV test from a provider, and having a sexually transmitted infection test in the past 12 months were not significantly associated with PrEP awareness. PrEP awareness was associated with being out to a healthcare provider (OR = 2.97, 95% CI=1.78, 4.96, p<0.001); being tested for HIV (OR=1.50, 95% CI = 1.06, 2.13, p = 0.023); and receiving condoms from an HIV/AIDS CBO (OR = 2.59, 95% CI = 1.43, 4.64, p = 0.001). By contrast, HIV testing was significantly associated with most forms of healthcare contact. Conclusions PrEP awareness is not associated with most forms of healthcare contact, highlighting the need for guidelines and trainings to support provider discussion of PrEP with MSM. PMID:27662698

Effects of Pre-exposure Prophylaxis for the Prevention of HIV Infection on Sexual Risk Behavior in Men Who Have Sex with Men: A Systematic Review and Meta-analysis.

PubMed

Traeger, Michael W; Schroeder, Sophia E; Wright, Edwina J; Hellard, Margaret E; Cornelisse, Vincent J; Doyle, Joseph S; Stoové, Mark A

2018-03-02

HIV pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM. We conducted a systematic review of open-label trials and observational studies published to August 2017 reporting sexual risk outcomes (STI diagnoses, condom use, number of sexual partners) in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis and a qualitative review and risk of bias assessment were performed. Sixteen observational studies and one open-label trial met selection criteria. Eight studies with 4388 participants reported STI prevalence and 13 studies with 5008 participants reported change in condom use. PrEP use was associated with a significant increase in rectal chlamydia (odds ratio [OR]=1.59; 95%CI 1.19-2.13; p=0.002; heterogeneity I 2=23%) and an increase in any STI diagnosis (OR=1.24; 95%CI 0.99-1.54; p=0.059; I 2=50%). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users. Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies.

Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

PubMed

van Zeller, Mafalda; Mota, Patrícia Caetano; Amorim, Adelina; Viana, Paulo; Martins, Paula; Gaspar, Luís; Hespanhol, Venceslau; Gomes, Isabel

2012-01-01

Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

A multimedia electronic patient record (ePR) system for image-assisted minimally invasive spinal surgery.

PubMed

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, H K

2010-05-01

This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on image-assisted minimally invasive spinal surgery as a clinical application. Three clinical phases of minimally invasive spinal surgery workflow in Pre-Op, Intra-Op, and Post-Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a minimally invasive spinal surgery clinical site with user training and support for daily use. A step-by-step approach was introduced to develop a multimedia ePR system for imaging-assisted minimally invasive spinal surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed.

Précis of Simple heuristics that make us smart.

PubMed

Todd, P M; Gigerenzer, G

2000-10-01

How can anyone be rational in a world where knowledge is limited, time is pressing, and deep thought is often an unattainable luxury? Traditional models of unbounded rationality and optimization in cognitive science, economics, and animal behavior have tended to view decision-makers as possessing supernatural powers of reason, limitless knowledge, and endless time. But understanding decisions in the real world requires a more psychologically plausible notion of bounded rationality. In Simple heuristics that make us smart (Gigerenzer et al. 1999), we explore fast and frugal heuristics--simple rules in the mind's adaptive toolbox for making decisions with realistic mental resources. These heuristics can enable both living organisms and artificial systems to make smart choices quickly and with a minimum of information by exploiting the way that information is structured in particular environments. In this précis, we show how simple building blocks that control information search, stop search, and make decisions can be put together to form classes of heuristics, including: ignorance-based and one-reason decision making for choice, elimination models for categorization, and satisficing heuristics for sequential search. These simple heuristics perform comparably to more complex algorithms, particularly when generalizing to new data--that is, simplicity leads to robustness. We present evidence regarding when people use simple heuristics and describe the challenges to be addressed by this research program.

Activation of Pathogenesis-related Genes by the Rhizobacterium, Bacillus sp. JS, Which Induces Systemic Resistance in Tobacco Plants.

PubMed

Kim, Ji-Seong; Lee, Jeongeun; Lee, Chan-Hui; Woo, Su Young; Kang, Hoduck; Seo, Sang-Gyu; Kim, Sun-Hyung

2015-06-01

Plant growth promoting rhizobacteria (PGPR) are known to confer disease resistance to plants. Bacillus sp. JS demonstrated antifungal activities against five fungal pathogens in in vitro assays. To verify whether the volatiles of Bacillus sp. JS confer disease resistance, tobacco leaves pre-treated with the volatiles were damaged by the fungal pathogen, Rhizoctonia solani and oomycete Phytophthora nicotianae. Pre-treated tobacco leaves had smaller lesion than the control plant leaves. In pathogenesis-related (PR) gene expression analysis, volatiles of Bacillus sp. JS caused the up-regulation of PR-2 encoding β-1,3-glucanase and acidic PR-3 encoding chitinase. Expression of acidic PR-4 encoding chitinase and acidic PR-9 encoding peroxidase increased gradually after exposure of the volatiles to Bacillus sp. JS. Basic PR-14 encoding lipid transfer protein was also increased. However, PR-1 genes, as markers of salicylic acid (SA) induced resistance, were not expressed. These results suggested that the volatiles of Bacillus sp. JS confer disease resistance against fungal and oomycete pathogens through PR genes expression.

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

PubMed

Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

2018-05-21

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an • OH pulse reduced to background the • OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

Binding characteristics of the ovine membrane progesterone receptor alpha and expression of the receptor during the estrous cycle

PubMed Central

Ashley, Ryan L; Arreguin-Arevalo, J Alejandro; Nett, Terry M

2009-01-01

Background Classically, progesterone has been thought to act only through the well-known genomic pathway involving hormone binding to nuclear receptors and subsequent modulation of gene expression. However, there is increasing evidence for rapid, non-genomic effects of progesterone in a variety of mammalian tissues and it is possible that a membrane PR (mPR) is causing these events. We recently isolated and characterized an ovine mPR referred to as mPR-alpha, distinct from the nuclear PR. Based on predicted structural analysis, the ovine mPR-alpha possesses seven transmembrane domains typical of G protein-coupled receptors. Despite the homology to other reported mPRs, information pertaining to the steroid binding characteristics of the ovine mPR-alpha was lacking. Additionally, the ovine mPR-alpha transcript has been identified in the hypothalamus, pituitary, uterus, ovary and corpus luteum, yet changes in expression of the ovine mPR-alpha in these tissues were not known. Consequently, the purpose of this work was to determine the steroid binding characteristics of the ovine mPR-alpha and to investigate possible changes in expression of the ovine mPR-alpha in reproductive tissues throughout the estrous cycle. Methods Binding studies were performed using crude membrane fractions from CHO cells expressing the mPR-alpha. Using quantitative Real-time PCR we determined the expression pattern of mRNA for the ovine mPR-alpha during the ovine estrous cycle in tissues known to express the mPR-alpha. Jugular blood samples were also collected and analyzed for serum concentrations of P4 to ensure ewes were at the appropriate stage of their cycle. Results Only progesterone, 20alpha-hydroxyprogesterone and 17alpha-hydroxyprogesterone were able to displace binding of 3H-P4 (P < 0.001) to membrane fractions from CHO cells expressing ovine mPR-alpha. The average B-max and Kd values for three separate experiments were 624 +/- 119 fmol/micro gram protein and 122 +/- 50 nM, respectively. Significant changes in expression of mRNA for the mPR-alpha during the estrous cycle were noted in the corpus luteum and uterus. Conclusion The mPR-alpha specifically binds progestins and its expression was correlated to progesterone secretion during the ovine estrous cycle. Results from the present studies suggest that mPR-alpha may have an important physiological role during the ovine estrous cycle. PMID:19432978

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

PubMed Central

Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

Chronic wasting disease prion infection of differentiated neurospheres.

PubMed

Iwamaru, Yoshifumi; Mathiason, Candace K; Telling, Glenn C; Hoover, Edward A

2017-07-04

A possible strategy to develop more diverse cell culture systems permissive to infection with naturally occurring prions is to exploit culture of neurospheres from transgenic mice expressing the normal prion protein (PrP) of the native host species. Accordingly, we developed differentiated neurosphere cultures from the cervid PrP-expressing mice to investigate whether this in vitro system would support replication of non-adapted cervid-origin chronic wasting disease (CWD) prions. Here we report the successful amplification of disease-associated PrP in differentiated neurosphere cultures within 3 weeks after exposure to CWD prions from both white-tailed deer or elk. This neurosphere culture system provides a new in vitro tool that can be used to assess non-adapted CWD prion propagation and transmission.

Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis

PubMed Central

Baeten, Jared; Celum, Connie

2013-01-01

Pre-exposure prophylaxis (PrEP), in which HIV uninfected persons use oral or topical antiretroviral medications to protect against HIV acquisition, is a promising new HIV prevention strategy. The biologic rationale for evaluation of PrEP for sexual HIV prevention included non-human primate models and antiretroviral prophylaxis for HIV-exposed infants. Proof-of-concept that PrEP protects against sexual HIV acquisition has been demonstrated in four clinical trials, which used the antiretroviral medication tenofovir, either as a vaginal gel or as daily oral tenofovir disoproxil fumarate, alone or co-formulated with emtricitabine. Importantly, however, two trials failed to demonstrate HIV protection with PrEP, with low adherence to daily use of PrEP the leading hypothesis for lack of efficacy. Next steps in the field include rigorous evaluation of uptake and adherence to PrEP in implementation settings and research into ‘next-generation’ PrEP agents with longer half-life and less user-dependence. PMID:23020883

Chemical partitioning for the Co--Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase

DOE PAGES

Zhou, S. H.; Kramer, M. J.; Meng, F. Q.; ...

2015-11-14

Co 5Pr-D2 d is promising permanent magnet. Due to its peritectic formation feature, there is a synthetic challenge to produce single Co 5Pr-D2 d phase. The object of our study is to assess thermodynamic pathways for crystalline phases under far-from-equilibrium conditions by combining first-principles calculations and experimental measurements into a robust description of the thermodynamic behavior. The energetic calculations, temperature and time dependent phase selections are predicted under varying degrees of chemical partitioning. Our calculation to assess the chemical partitioning-temperatures indicates that the major magnetic compounds: Co 17Pr 2-α, Co 5Pr-D2 d, Co 19Pr 5-β, and Co 7Pr 2-χ formmore » from a congruent manner to eutectic reactions with decreasing cooling rate. The compositions of the compounds from these highly driven liquids can be far from equilibrium.« less

Speech Understanding in Noise in the Bison Command, Control, Communications and Intelligence (C3I) Mobile Command Post (MCP)

DTIC Science & Technology

2010-12-01

messages étaient présentés au moyen des haut-parleurs en présence de bruit dans le véhicule. Même si des notes relativement faibles ont été obtenues...Research Ethics Committee. Each subject read the protocol and provided informed consent before participating. The terms and conditions of remuneration

Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora

PubMed Central

Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

2016-01-01

This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana.

PubMed

Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M

2015-03-01

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Forecasting Global Rainfall for Points Using ECMWF's Global Ensemble and Its Applications in Flood Forecasting

NASA Astrophysics Data System (ADS)

Pillosu, F. M.; Hewson, T.; Mazzetti, C.

2017-12-01

Prediction of local extreme rainfall has historically been the remit of nowcasting and high resolution limited area modelling, which represent only limited areas, may not be spatially accurate, give reasonable results only for limited lead times (<2 days) and become prohibitively expensive at global scale. ECMWF/EFAS/GLOFAS have developed a novel, cost-effective and physically-based statistical post-processing software ("ecPoint-Rainfall, ecPR", operational in 2017) that uses ECMWF Ensemble (ENS) output to deliver global probabilistic rainfall forecasts for points up to day 10. Firstly, ecPR applies a new notion of "remote calibration", which 1) allows us to replicate a multi-centennial training period using only one year of data, and 2) provides forecasts for anywhere in the world. Secondly, the software applies an understanding of how different rainfall generation mechanisms lead to different degrees of sub-grid variability in rainfall totals, and of where biases in the model can be improved upon. A long-term verification has shown that the post-processed rainfall has better reliability and resolution at every lead time if compared with ENS, and for large totals, ecPR outputs have the same skill at day 5 that the raw ENS has at day 1 (ROC area metric). ecPR could be used as input for hydrological models if its probabilistic output is modified accordingly to the inputs requirements for hydrological models. Indeed, ecPR does not provide information on where the highest total is likely to occur inside the gridbox, nor on the spatial distribution of rainfall values nearby. "Scenario forecasts" could be a solution. They are derived from locating the rainfall peak in sensitive positions (e.g. urban areas), and then redistributing the remaining quantities in the gridbox modifying traditional spatial correlation characterization methodologies (e.g. variogram analysis) in order to take account, for instance, of the type of rainfall forecast (stratiform, convective). Such an approach could be a turning point in the field of medium-range global real-time riverine flood forecasts. This presentation will illustrate for ecPR 1) system calibration, 2) operational implementation, 3) long-term verification, 4) future developments, and 5) early ideas for the application of ecPR outputs in hydrological models.

Commentary: the value of PrEP for people who inject drugs.

PubMed

Coleman, Rosalind L; McLean, Susie

2016-01-01

The offer of pre-exposure prophylaxis (PrEP) is recommended as an additional option for HIV prevention for people at substantial risk of HIV infection as part of combination HIV prevention approaches. Implementing this depends on integrating PrEP in public health programmes that address risky practices with evidence-based interventions, and that operate in an enabling legal and policy environment for the delivery of health services to those at higher risk of HIV infection. What does this recommendation mean in terms of the diverse range of HIV prevention needs of key populations, some of whom are so discriminated against that they exist essentially outside formal systems such as national public health services, and for whom a substantial risk of HIV is part of a larger adverse and hostile situation? We discuss this question with reference to people who inject drugs, informed by concerns and comments that emerged from a series of consultations. HIV prevention is part of a spectrum of injecting drug users' priorities, and their access and uptake of HIV prevention services is contingent on their wider "risk environment." The need to address structural barriers to services and human rights violations, and to improve access to comprehensive harm reduction programmes are of prime importance and would have higher value than a mono-focus on HIV prevention. Where existing harm reduction activities are inadequate, fragile or dependent on external donors, shifts in funding priorities, including, for example, towards PrEP, could threaten investment in the broader programmes. For these reasons, it cannot be assumed that PrEP promotion will always be supported by people who inject drugs.The sexual partners of people who inject drugs, non-opioid users who also inject and for whom there is no established substitution treatment, as well as drug users who are unable to negotiate safe sex may value PrEP. As for all key populations, the involvement of people who inject drugs in shaping services for their consumption is vital and too often ignored. For people who inject drugs and who experience discrimination, violence or harassment, implementation of PrEP should be guided by understanding and engaging with their interconnected range of needs, risk practices, priorities and options. The differentiated needs of sub-populations that inject a range of drugs, and their sexual partners, require further exploration.

New Paranal Views

NASA Astrophysics Data System (ADS)

2001-01-01

Last year saw very good progress at ESO's Paranal Observatory , the site of the Very Large Telescope (VLT). The third and fourth 8.2-m Unit Telescopes, MELIPAL and YEPUN had "First Light" (cf. PR 01/00 and PR 18/00 ), while the first two, ANTU and KUEYEN , were busy collecting first-class data for hundreds of astronomers. Meanwhile, work continued towards the next phase of the VLT project, the combination of the telescopes into the VLT Interferometer. The test instrument, VINCI (cf. PR 22/00 ) is now being installed in the VLTI Laboratory at the centre of the observing platform on the top of Paranal. Below is a new collection of video sequences and photos that illustrate the latest developments at the Paranal Observatory. The were obtained by the EPR Video Team in December 2000. The photos are available in different formats, including "high-resolution" that is suitable for reproduction purposes. A related ESO Video News Reel for professional broadcasters will soon become available and will be announced via the usual channels. Overview Paranal Observatory (Dec. 2000) Video Clip 02a/01 [MPEG - 4.5Mb] ESO PR Video Clip 02a/01 "Paranal Observatory (December 2000)" (4875 frames/3:15 min) [MPEG Video+Audio; 160x120 pix; 4.5Mb] [MPEG Video+Audio; 320x240 pix; 13.5 Mb] [RealMedia; streaming; 34kps] [RealMedia; streaming; 200kps] ESO Video Clip 02a/01 shows some of the construction activities at the Paranal Observatory in December 2000, beginning with a general view of the site. Then follow views of the Residencia , a building that has been designed by Architects Auer and Weber in Munich - it integrates very well into the desert, creating a welcome recreational site for staff and visitors in this harsh environment. The next scenes focus on the "stations" for the auxiliary telescopes for the VLTI and the installation of two delay lines in the 140-m long underground tunnel. The following part of the video clip shows the start-up of the excavation work for the 2.6-m VLT Survey Telescope (VST) as well as the location known as the "NTT Peak", now under consideration for the installation of the 4-m VISTA telescope. The last images are from to the second 8.2-m Unit Telescope, KUEYEN, that has been in full use by the astronomers with the UVES and FORS2 instruments since April 2000. ESO PR Photo 04a/01 ESO PR Photo 04a/01 [Preview - JPEG: 466 x 400 pix - 58k] [Normal - JPEG: 931 x 800 pix - 688k] [Hires - JPEG: 3000 x 2577 pix - 7.6M] Caption : PR Photo 04a/01 shows an afternoon view from the Paranal summit towards East, with the Base Camp and the new Residencia on the slope to the right, above the valley in the shadow of the mountain. ESO PR Photo 04b/01 ESO PR Photo 04b/01 [Preview - JPEG: 791 x 400 pix - 89k] [Normal - JPEG: 1582 x 800 pix - 1.1Mk] [Hires - JPEG: 3000 x 1517 pix - 3.6M] PR Photo 04b/01 shows the ramp leading to the main entrance to the partly subterranean Residencia , with the steel skeleton for the dome over the central area in place. ESO PR Photo 04c/01 ESO PR Photo 04c/01 [Preview - JPEG: 498 x 400 pix - 65k] [Normal - JPEG: 995 x 800 pix - 640k] [Hires - JPEG: 3000 x 2411 pix - 6.6M] PR Photo 04c/01 is an indoor view of the reception hall under the dome, looking towards the main entrance. ESO PR Photo 04d/01 ESO PR Photo 04d/01 [Preview - JPEG: 472 x 400 pix - 61k] [Normal - JPEG: 944 x 800 pix - 632k] [Hires - JPEG: 3000 x 2543 pix - 5.8M] PR Photo 04d/01 shows the ramps from the reception area towards the rooms. The VLT Interferometer The Delay Lines consitute a most important element of the VLT Interferometer , cf. PR Photos 26a-e/00. At this moment, two Delay Lines are operational on site. A third system will be integrated early this year. The VLTI Delay Line is located in an underground tunnel that is 168 metres long and 8 metres wide. This configuration has been designed to accommodate up to eight Delay Lines, including their transfer optics in an ideal environment: stable temperature, high degree of cleanliness, low levels of straylight, low air turbulence. The positions of the Delay Line carriages are computed to adjust the Optical Path Lengths requested for the fringe pattern observation. The positions are controlled in real time by a laser metrology system, specially developed for this purpose. The position precision is about 20 nm (1 nm = 10 -9 m, or 1 millionth of a millimetre) over a distance of 120 metres. The maximum velocity is 0.50 m/s in position mode and maximum 0.05 m/s in operation. The system is designed for 25 year of operation and to survive earthquake up to 8.6 magnitude on the Richter scale. The VLTI Delay Line is a three-year project, carried out by ESO in collaboration with Dutch Space Holdings (formerly Fokker Space) and TPD-TNO . VLTI Delay Lines (December 2000) - ESO PR Video Clip 02b/01 [MPEG - 3.6Mb] ESO PR Video Clip 02b/01 "VLTI Delay Lines (December 2000)" (2000 frames/1:20 min) [MPEG Video+Audio; 160x120 pix; 3.6Mb] [MPEG Video+Audio; 320x240 pix; 13.7 Mb] [RealMedia; streaming; 34kps] [RealMedia; streaming; 200kps] ESO Video Clip 02b/00 shows the Delay Lines of the VLT Interferometer facility at Paranal during tests. One of the carriages is moving on 66-metre long rectified rails, driven by a linear motor. The carriage is equipped with three wheels in order to preserve high guidance accuracy. Another important element is the Cat's Eye that reflects the light from the telescope to the VLT instrumentation. This optical system is made of aluminium (including the mirrors) to avoid thermo-mechanical problems. ESO PR Photo 04e/01 ESO PR Photo 04e/01 [Preview - JPEG: 400 x 402 pix - 62k] [Normal - JPEG: 800 x 804 pix - 544k] [Hires - JPEG: 3000 x 3016 pix - 6.2M] Caption : PR Photo 04e/01 shows one of the 30 "stations" for the movable 1.8-m Auxiliary Telescopes. When one of these telescopes is positioned ("parked") on top of it, The light will be guided through the hole towards the Interferometric Tunnel and the Delay Lines. ESO PR Photo 04f/01 ESO PR Photo 04f/01 [Preview - JPEG: 568 x 400 pix - 96k] [Normal - JPEG: 1136 x 800 pix - 840k] [Hires - JPEG: 3000 x 2112 pix - 4.6M] PR Photo 04f/01 shows a general view of the Interferometric Tunnel and the Delay Lines. ESO PR Photo 04g/01 ESO PR Photo 04g/01 [Preview - JPEG: 406 x 400 pix - 62k] [Normal - JPEG: 812 x 800 pix - 448k] [Hires - JPEG: 3000 x 2956 pix - 5.5M] PR Photo 04g/01 shows one of the Delay Line carriages in parking position. The "NTT Peak" The "NTT Peak" is a mountain top located about 2 km to the north of Paranal. It received this name when ESO considered to move the 3.58-m New Technology Telescope from La Silla to this peak. The possibility of installing the 4-m VISTA telescope (cf. PR 03/00 ) on this peak is now being discussed. ESO PR Photo 04h/01 ESO PR Photo 04h/01 [Preview - JPEG: 630 x 400 pix - 89k] [Normal - JPEG: 1259 x 800 pix - 1.1M] [Hires - JPEG: 3000 x 1907 pix - 5.2M] PR Photo 04h/01 shows the view from the "NTT Peak" towards south, vith the Paranal mountain and the VLT enclosures in the background. ESO PR Photo 04i/01 ESO PR Photo 04i/01 [Preview - JPEG: 516 x 400 pix - 50k] [Normal - JPEG: 1031 x 800 pix - 664k] [Hires - JPEG: 3000 x 2328 pix - 6.0M] PR Photo 04i/01 is a view towards the "NTT Peak" from the top of the Paranal mountain. The access road and the concrete pillar that was used to support a site testing telescope at the top of this peak are seen This is the caption to ESO PR Photos 04a-1/01 and PR Video Clips 02a-b/01 . They may be reproduced, if credit is given to the European Southern Observatory. The ESO PR Video Clips service to visitors to the ESO website provides "animated" illustrations of the ongoing work and events at the European Southern Observatory. The most recent clip was: ESO PR Video Clip 01/01 about the Physics On Stage Festival (11 January 2001) . Information is also available on the web about other ESO videos.

The use of technology to find sexual health information online among men who have sex with men in Hanoi, Vietnam, 2016.

PubMed

Nguyen, Minh X; Krishnan, Aparna; Le, Giang M; Nguyen, Quynh T; Bhadra, Nia M; Nguyen, Sang M; Miller, William C; Go, Vivian F

2018-04-01

In an era where mobile phones and computers are ubiquitous, technology-based interventions to reduce HIV and other sexually transmitted infections (STIs) have great potential to reach high-risk groups, including men who have sex with men (MSM). This study aimed to examine technology usage to find sexual health information online among MSM in Hanoi, Vietnam. A cross-sectional study of 205 MSM in Hanoi was conducted from February to May 2016. Overall, 50.7% of participants reported having used a smartphone, computer, or tablet to find HIV/STI testing locations in the past year, and 75.1% reported having used such devices to find other HIV/STI information online. Unemployment (adjusted prevalence ratio [aPR]: 1.13, 95%CI: 1.00-1.28) and having been tested for HIV (aPR: 1.27, 95%CI: 1.07-1.51) were significantly associated with using technology to find online sexual health information. MSM who had ever exchanged sex for money or drugs (aPR: 0.80; 95%CI: 0.68-0.94) were less likely to use technology to find sexual health information online. Technology is a promising platform for HIV/STI prevention programs among MSM, with the potential to reach different subgroups. Further efforts to develop technology-based interventions tailored to the needs of the MSM communities in Hanoi and to encourage MSM who were not currently seeking sexual health information and testing services online to do so are necessary.

Comprehensive programs for preventing pressure ulcers: a review of the literature.

PubMed

Niederhauser, Andrea; VanDeusen Lukas, Carol; Parker, Victoria; Ayello, Elizabeth A; Zulkowski, Karen; Berlowitz, Dan

2012-04-01

The objective of this study was to examine the evidence supporting the combined use of interventions to prevent pressure ulcers (PrUs) in acute care and long-term-care facilities. A systematic review of the literature describing multifaceted PrU prevention programs was performed. Articles were included if they described an intervention implemented in acute care settings or long-term-care facilities, incorporated more than 1 intervention component, involved a multidisciplinary team, and included information about outcomes related to the intervention. Twenty-four studies were identified. Recurring components used in the development and implementation of PrU prevention programs included preparations prior to the start of a program, PrU prevention best practices, staff education, clinical monitoring and feedback, skin care champions, and cues to action. Ten studies reported PrU prevalence rates; 9 of them reported decreased prevalence rates at the end of their programs. Of the 6 studies reporting PrU incidence rates, 5 reported a decrease in incidence rates. Four studies measured care processes: 1 study reported an overall improvement; 2 studies reported improvement on some, but not all, measures; and 1 study reported no change. There is a growing literature describing multipronged, multidisciplinary interventions to prevent PrUs in acute care settings and long-term-care facilities. Outcomes reported in these studies suggest that such programs can be successful in reducing PrU prevalence or incidence rates. However, to strengthen the level of evidence, sites should be encouraged to rigorously evaluate their programs and to publish their results.

Health Information Brokers in the General Population: An Analysis of the Health Information National Trends Survey 2013-2014.

PubMed

Cutrona, Sarah L; Mazor, Kathleen M; Agunwamba, Amenah A; Valluri, Sruthi; Wilson, Patrick M; Sadasivam, Rajani S; Finney Rutten, Lila J

2016-06-03

Health information exchanged between friends or family members can influence decision making, both for routine health questions and for serious health issues. A health information broker is a person to whom friends and family turn for advice or information on health-related topics. Characteristics and online behaviors of health information brokers have not previously been studied in a national population. The objective of this study was to examine sociodemographic characteristics, health information seeking behaviors, and other online behaviors among health information brokers. Data from the Health Information National Trends Survey (2013-2014; n=3142) were used to compare brokers with nonbrokers. Modified Poisson regression was used to examine the relationship between broker status and sociodemographics and online information seeking. Over half (54.8%) of the respondents were consulted by family or friends for advice or information on health topics (ie, they acted as health information brokers). Brokers represented 54.1% of respondents earning <$20,000 yearly and 56.5% of respondents born outside the United States. Women were more likely to be brokers (PR 1.34, 95% CI 1.23-1.47) as were those with education past high school (PR 1.42, CI 1.22-1.65). People aged ≥75 were less likely to be brokers as compared to respondents aged 35-49 (PR 0.81, CI 0.67-0.99). Brokers used the Internet more frequently for a variety of online behaviors such as seeking health information, creating and sharing online content, and downloading health information onto a mobile device; and also reported greater confidence in obtaining health information online. More than 50% of adults who responded to this national survey, including those with low income and those born abroad, were providing health information or advice to friends and family. These individuals may prove to be effective targets for initiatives supporting patient engagement and disease management, and may also be well-positioned within their respective social networks to propagate health messages.

75 FR 68512 - Proposed Christmas Tree Promotion, Research, and Information Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-08

...-0008-PR-1A] RIN 0581-AD00 Proposed Christmas Tree Promotion, Research, and Information Order AGENCY... rule invites comments on the establishment of an industry-funded promotion, research, and information program for fresh cut Christmas trees. The proposed Christmas Tree Promotion, Research, and Information...

[Accidents on Iceland's most dangerous roads].

PubMed

Bjarnason, Thóroddur; Arnarsson, Sveinn

2012-02-01

The objective of this paper was to identify the most dangerous segments of the Icelandic road system in terms of the number of accidents pr km and the rate of accidents pr million km travelled. First to identify the segments where the number of accidents is highest and where the risk of the individual traveller is the greatest. Second to evaluate if the association between the number and the rate of accidents is positive or negative. Third to identify the road segments that are the most dangerous in the sense of many accidents and great risk to individual travellers. Main roads outside urban centers were divided into 45 segments that were on average 78 km in length. Infrequently travelled roads and roads within urban centers were omitted. Information on the length of roads, traffic density and number of accidents was used to calculate the number of accidents per km and the rate of accidents per million km travelled. The correlation between the number and rate of accidents was calculated and the most dangerous road segments were identified by the average rank order on both dimensions. Most accidents pr km occurred on the main roads to and from the capital region, but also east towards Hvolsvöllur, north towards Akureyri and in the Mideast region of the country. The rate of accidents pr million km travelled was highest in the northeast region, in northern Snæfellsnes and in the Westfjords. The most dangerous roads on both dimensions were in Mideast, northern Westfjords, in the north between Blönduós and Akureyri and in northern Snæfellsnes. Most accidents pr km occurred on roads with a low accident rate pr million km travelled. It is therefore possible to reduce accidents the most by increasing road safety where it is already the greatest but that would however increase inequalities in road safety. Policy development in transportation is therefore in part a question of priorities in healthcare. Individual equality in safety and health are not always fully compatible with economic concerns and the interests of the majority.

NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

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

Furukawa, Ayako; Okamura, Hideyasu; Morishita, Ryo

2012-08-24

Highlights: Black-Right-Pointing-Pointer Protease (PR) of XMR virus (XMRV) was successfully synthesized with cell-free system. Black-Right-Pointing-Pointer Interface of XMRV PR with an inhibitor, amprenavir (APV), was identified with NMR. Black-Right-Pointing-Pointer Structural heterogeneity is induced for two PR protomers in the APV:PR = 1:2 complex. Black-Right-Pointing-Pointer Structural heterogeneity is transmitted even to distant regions from the interface. Black-Right-Pointing-Pointer Long-range transmission of structural change may be utilized for drug discovery. -- Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a virus created through recombination of two murine leukemia proviruses under artificial conditions during the passage of human prostate cancer cells in athymic nudemore » mice. The homodimeric protease (PR) of XMRV plays a critical role in the production of functional viral proteins and is a prerequisite for viral replication. We synthesized XMRV PR using the wheat germ cell-free expression system and carried out structural analysis of XMRV PR in a complex with an inhibitor, amprenavir (APV), by means of NMR. Five different combinatorially {sup 15}N-labeled samples were prepared and backbone resonance assignments were made by applying Otting's method, with which the amino acid types of the [{sup 1}H, {sup 15}N] HSQC resonances were automatically identified using the five samples (Wu et al., 2006) . A titration experiment involving APV revealed that one APV molecule binds to one XMRV PR dimer. For many residues, two distinct resonances were observed, which is thought to be due to the structural heterogeneity between the two protomers in the APV:XMRV PR = 1:2 complex. PR residues at the interface with APV have been identified on the basis of chemical shift perturbation and identification of the intermolecular NOEs by means of filtered NOE experiments. Interestingly, chemical shift heterogeneity between the two protomers of XMRV PR has been observed not only at the interface with APV but also in regions apart from the interface. This indicates that the structural heterogeneity induced by the asymmetry of the binding of APV to the XMRV PR dimer is transmitted to distant regions. This is in contrast to the case of the APV:HIV-1 PR complex, in which the structural heterogeneity is only localized at the interface. Long-range transmission of the structural change identified for the XMRV PR complex might be utilized for the discovery of a new type of drug.« less

Pre-exposure Prophylaxis (PrEP) Use, Seroadaptation, and Sexual Behavior Among Men Who Have Sex with Men, San Francisco, 2004-2014.

PubMed

Chen, Yea-Hung; Snowden, Jonathan M; McFarland, Willi; Raymond, H Fisher

2016-12-01

The Food and Drug Administration approved pre-exposure prophylaxis (PrEP) to prevent HIV infection, and the Centers for Disease Control and Prevention has presented PrEP as a prevention option for groups at high risk such as men who have sex with men (MSM). Intervention data provide some information on how PrEP affects sexual behavior of MSM in trials, open label extensions, or clinics. However, it is unclear whether sexual risk and preventive behavioral patterns are changing in the population as a whole as PrEP becomes more widely available, whether due to PrEP use or other factors. We examined trends in PrEP use, numbers of condomless anal sex partners, consistent condom use, and seroadaptive strategies in San Francisco-a city which has actively promoted PrEP-using data from National HIV Behavioral Surveillance (NHBS). NHBS recruited 1211, 383, 373, and 268 HIV-negative MSM in 2004, 2008, 2011, and 2014, respectively. PrEP use increased from zero in 2004, 2008, and 2011 to 9.6 % in 2014. The proportion of men with no condomless anal sex partners dropped from 60.6 % in 2004, to 58.2 % in 2008, to 54.2 % in 2011, to 40.2 % in 2014. Consistent condom use decreased from 36.8 % in 2004, and 30.5 % in 2008 and 2011, to 18.3 % in 2014. PrEP's introduction and scale-up enters in a pre-existing trend of decreasing condom use and increasing sexually transmitted infections among MSM which may be accelerating in recent years. While PrEP use should be scaled up as a prevention option among those who would benefit most, we believe that public health officials need to be realistic about the possibility that condom use could very well continue to decline as PrEP use increases, and to an extent that may not be directly or indirectly offset by PrEP.

Search for new phases in the Praseodymium-Silicon system

NASA Astrophysics Data System (ADS)

de La Venta, Jose; Basaran, Ali C.; Grant, Ted; Gallardo-Amores, J.; Ramirez, J. G.; Suchomel, M. R.; Alario-Franco, M. A.; Fisk, Zachary; Schuller, Ivan K.

2013-03-01

We searched for new superconducting and magnetic phases in the Pr-Si system using high-pressure high-temperature and conventional arc melting syntheses. High pressure synthesis is a unique technique which allows incorporation of elements into compounds which otherwise cannot be synthesized at ambient pressure Both high and low Si concentration areas of the phase diagram were explored. To investigate the high Si concentration compounds, PrSi2 with an excess of Si was subjected to HP-HT synthesis. To explore the high Pr concentration binary compound Pr5Si3, we have synthesized undoped Pr5Si3 as well as different samples doped with C or B. High resolution X-ray powder diffraction, Magnetic Field Modulated Microwave Spectroscopy and magnetic characterization found that the addition of C gave rise to multiple previously-unknown ferromagnetic phases. Furthermore, X-ray refinement of the undoped samples confirmed the existence of the so far unconfirmed Pr3Si2 phase. Work supported by AFOSR MURI #F49550-09-1-0577 dedicated to Search for New Superconductors for Energy and Power A. Use of the Advanced Photon Source at ANL was supported by the U. S. DoE, Office of Basic Energy Sciences, Contract No. DE-AC02-06CH11357.

Evaluation of a metering, mixing, and dispensing system for mixing polysulfide adhesive

NASA Technical Reports Server (NTRS)

Evans, Kurt B.

1989-01-01

Tests were performed to evaluate whether a metered mixing system can mix PR-1221 polysulfide adhesive as well as or better than batch-mixed adhesive; also, to evaluate the quality of meter-mixed PR-1860 and PS-875 polysulfide adhesives. These adhesives are candidate replacements for PR-1221 which will not be manufactured in the future. The following material properties were evaluated: peel strength, specific gravity and adhesive components of mixed adhesives, Shore A hardness, tensile adhesion strength, and flow rate. Finally, a visual test called the butterfly test was performed to observe for bubbles and unmixed adhesive. The results of these tests are reported and discussed.

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices.

PubMed

Sevelius, Jae M; Deutsch, Madeline B; Grant, Robert

2016-01-01

Globally, transgender ("trans") women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population. Available information, including but not limited to existing scientific literature, about trans women and PrEP was reviewed and critiqued based on author expertise, including PrEP clinical trials and rollout. To date, PrEP demonstration projects and clinical trials have largely excluded trans women, or have not included them in a meaningful way. Data collection strategies that fail to identify trans women in clinical trials and research further limit the ability to draw conclusions about trans women's unique needs and devise strategies to meet them. Gender-affirming providers and clinic environments are essential components of any sexual health programme that aims to serve trans women, as they will largely avoid settings that may result in stigmatizing encounters and threats to their identities. While there is currently no evidence to suggest drug-drug interactions between PrEP and commonly used feminizing hormone regimens, community concerns about potential interactions may limit interest in and uptake of PrEP among trans women. In scaling up PrEP for trans women, it is essential to engage trans communities, utilize trans-inclusive research and marketing strategies and identify and/or train healthcare providers to provide gender-affirming healthcare to trans women, including transition-related care such as hormone provision. PrEP implementation guidelines must consider and address trans women's unique barriers and facilitators to uptake and adherence.

Event-level analysis of alcohol consumption and condom use in partnership contexts among men who have sex with men and transgender women in Lima, Peru.

PubMed

Delgado, Jeanne R; Segura, Eddy R; Lake, Jordan E; Sanchez, Jorge; Lama, Javier R; Clark, Jesse L

2017-01-01

We explored the association between alcohol use and condomless receptive (CRAI) and insertive (CIAI) anal intercourse within partnership contexts of men who have sex with men (MSM) and transgender women (TGW) in Lima, Peru. From 2012-2014, we surveyed men and TGW (n=1607) who reported anal intercourse with ≥1 male or TGW. Alcohol use with up to 3 sexual partners during the prior 90days was evaluated. Bivariate and multivariate analyses used generalized estimating equations to assess event-level associations between alcohol use, CRAI, CIAI, and partnership characteristics while adjusting for participant clustering from multiple partners. Of 4774 sexual partnerships reported, 48% were casual, 34% primary, 10% anonymous, and 8% commercial. Alcohol use preceding sex was significantly (p<0.05) associated with CRAI (PR=1.26) and CIAI (PR=1.37). Partnership characteristics significantly associated with alcohol use included commercial sex work (PR=2.21) and trended (p<0.10) towards alcohol use with casual (PR=1.16), transgender (PR=1.48), and moderno ("versatile"; PR=1.17) partners. CRAI and CIAI were more common among participants who reported knowing they (PR=1.52; PR=1.41, respectively) or their partner (PR=1.47; PR=1.44, respectively) was HIV-uninfected. Yet, only CIAI (PR=1.42) was more commonly reported with known HIV-infected partners. Participants who drank alcohol prior to sex were less likely to know their partner's HIV serostatus. Alcohol use prior to intercourse was associated with CRAI and CIAI, varied by partnership type, and may impair knowledge of partner HIV serostatus. Detailed knowledge of alcohol use within partner-specific contexts is essential for informing condom-based and alternative HIV prevention strategies for MSM and TGW in Peru. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices

PubMed Central

Sevelius, Jae M; Deutsch, Madeline B; Grant, Robert

2016-01-01

Introduction Globally, transgender (“trans”) women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population. Methods Available information, including but not limited to existing scientific literature, about trans women and PrEP was reviewed and critiqued based on author expertise, including PrEP clinical trials and rollout. Results To date, PrEP demonstration projects and clinical trials have largely excluded trans women, or have not included them in a meaningful way. Data collection strategies that fail to identify trans women in clinical trials and research further limit the ability to draw conclusions about trans women's unique needs and devise strategies to meet them. Gender-affirming providers and clinic environments are essential components of any sexual health programme that aims to serve trans women, as they will largely avoid settings that may result in stigmatizing encounters and threats to their identities. While there is currently no evidence to suggest drug-drug interactions between PrEP and commonly used feminizing hormone regimens, community concerns about potential interactions may limit interest in and uptake of PrEP among trans women. Conclusions In scaling up PrEP for trans women, it is essential to engage trans communities, utilize trans-inclusive research and marketing strategies and identify and/or train healthcare providers to provide gender-affirming healthcare to trans women, including transition-related care such as hormone provision. PrEP implementation guidelines must consider and address trans women's unique barriers and facilitators to uptake and adherence. PMID:27760683

Metallic Fuels Handbook

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

Janney, Dawn E.; Papesch, Cynthia A.; Burkes, Douglas E.

This is not a typical External Report--It is a Handbook. No Abstract is involved. This includes both Parts 1 and 2. The Metallic Fuels Handbook summarizes currently available information about phases and phase diagrams, heat capacity, thermal expansion, and thermal conductivity of elements and alloys in the U-Pu-Zr-Np-Am-La-Ce-Pr-Nd system. Although many sections are reviews and updates of material in previous versions of the Handbook [1, 2], this revision is the first to include alloys with four or more elements. In addition to presenting information about materials properties, the handbook attempts to provide information about how well each property is knownmore » and how much variation exists between measurements. Although it includes some results from models, its primary focus is experimental data.« less

Overcoming Etch Challenges on a 6″ Hg1- x Cd x Te MBE on Si Wafer

NASA Astrophysics Data System (ADS)

Apte, Palash; Norton, Elyse; Robinson, Solomon

2017-10-01

The effect of increasing photoresist (PR) thickness on the inductively coupled plasma (ICP) dry etched characteristics of a 6″ (c.15 cm) molecular beam epitaxy Hg1- x Cd x Te/Si wafer is investigated. It is determined that the Hg1- x Cd x Te etch rate (ER) does not vary significantly with a change in the PR thickness. Also, the vertical ER of the PR is seen to be independent of the PR thickness, but the lateral ER is seen to reduce significantly with increased PR thickness. Indeed, very little reduction in the pixel mesa area post-dry etch is seen for the thicker PR. Consequently, the trench sidewall angle is also seen to vary as a function of the PR thickness. Since ICP is the more attractive choice for dry etching Hg1- x Cd x Te, this simple, cost-effective way to extend the capabilities of dry etching (larger mesa top area post-dry etch, ability to create tailor-made trench sidewall angles for optimal conformal passivation deposition, and potential for reduced dry etch damage) described here would allow for the fabrication of next generation infrared detectors with increased yield and reduced cost. Although similar results have been presented using the electron cyclotron resonance system to dry etch Hg1- x Cd x Te, to the best of our knowledge, this is the first time that such results have been presented using an ICP system.

Willingness to use HIV pre-exposure prophylaxis among gay men, other men who have sex with men and transgender women in Myanmar.

PubMed

Draper, Bridget L; Fowkes, Freya J I; Oo, Zaw Min; Thein, Zaw Win; Aung, Poe Poe; Veronese, Vanessa; Ryan, Claire; Thant, Myo; Hughes, Chad; Stoové, Mark

2017-07-26

HIV pre-exposure prophylaxis (PrEP) has emerged as a key component of contemporary HIV combination prevention strategies. To explore the local suitability of PrEP, country-specific acceptability studies are needed to inform potential PrEP implementation. In the context of Myanmar, in addition to resource constraints, HIV service access by gay men, other men who have sex with men, and transgender women (GMT) continues to be constrained by legislative and community stigma and marginalization. We aimed to determine PrEP acceptability among GMT in Myanmar and explore the factors associated with willingness to use PrEP. GMT were recruited in Yangon and Mandalay through local HIV prevention outreach programmes in November and December 2014. Quantitative surveys were administered by trained peer educators and collected data on demographics, sexual risk, testing history and PrEP acceptability. A modified six-item PrEP acceptability scale classified self-reported HIV undiagnosed GMT as willing to use PrEP. Multivariable logistic regression identified factors associated with willingness to use PrEP. Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%). PrEP acceptability was high, with 270 (62%) GMT classified as willing to use PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05-3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82; 95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94; 95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The association between never or only occasionally using condoms with casual partners and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00-4.10). GMT who reported concern about side effects and long-term use of PrEP were less likely (aOR = 0.35; 95%CI = 0.21-0.59) to be willing to use PrEP. This is the first study to assess PrEP acceptability in Myanmar. Findings suggest PrEP is an acceptable prevention option among GMT in Myanmar, providing they are not required to pay for it. Implementation/demonstration projects are needed to explore the feasibility and cost-effectiveness of PrEP as a prevention option for GMT in Myanmar.

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis.

PubMed

Millet, Arnaud; Martin, Katherine R; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

2015-11-02

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

PubMed Central

Millet, Arnaud; Martin, Katherine R.; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A.; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

2015-01-01

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology. PMID:26436651

Knowledge, attitudes, and beliefs about HIV pre-exposure prophylaxis among US Air Force Health Care Providers

PubMed Central

Hakre, Shilpa; Blaylock, Jason M; Dawson, Peter; Beckett, Charmagne; Garges, Eric C; Michael, Nelson L; Danaher, Patrick J; Scott, Paul T; Okulicz, Jason F

2016-01-01

Abstract Providers are central to effective implementation of HIV pre-exposure prophylaxis (PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in the US Air Force (USAF) participated in a cross-sectional survey regarding knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated with PrEP knowledge were assessed in univariate and multivariate analyses. Among 403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed PrEP. In univariate analysis, years in practice, number of HIV-infected patients treated in the past 12 months, past prescription of antiretrovirals for HIV prevention, frequency of prescribing PrEP in the past 12 months, and ever being questioned by a patient about PrEP were associated with PrEP knowledge (P < 0.05). In multivariate analysis, providers who had ever prescribed antiretrovirals to prevent HIV (AOR: 2.37, 95% CI: 1.27–4.42) had greater odds of high PrEP knowledge. Despite concerns about medication side effects (overall 67%: PCP 68%, ID 85%) and prescribing PrEP without clear evidence (overall 60%: PCP 65%, ID 62%), 64% (PCP 65%, ID 85%) of participants indicated PrEP should be offered in the Military Health System and 68% (PCP 70%, ID 100%) disagreed with the statement that their patient population was not at risk for HIV infection. Successful PrEP implementation in the USAF will require continued education and training of primary care providers to improve knowledge and mitigate concerns about PrEP. PMID:27512869

Polar Intermetallics Pr 5Co 2Ge 3 and Pr 7Co 2Ge 4 With Planar Hydrocarbon-Like Metal Clusters

DOE PAGES

Lin, Qisheng; Aguirre, Kaiser; Saunders, Scott M.; ...

2017-06-19

Planar hydrocarbon-like metal clusters may foster new insights linking organic molecules with conjugated π-π bonding interactions and inorganic structures in terms of their bonding characteristics. However, such clusters are uncommon in polar intermetallics. Herein, we report two polar intermetallic phases, Pr 5Co 2Ge 3 and Pr 7Co 2Ge 4, both of which feature such planar metal clusters, viz., ethylene-like [Co 2Ge 4] clusters plus the concatenated forms and polyacene-like [Co 2Ge 2] n ribbons in Pr 5Co 2Ge 3, and 1,2,4,5-tetramethylbenzene-like [Co4Ge6] cluster in Pr 7Co 2Ge 4. Just as in the related planar organic structures, these metal-metalloid species aremore » dominated by covalent bonding interactions. Both compounds magnetically order at low temperature with net ferromagnetic components: Pr 5Co 2Ge 3 via a series of transitions below 150 K; and Pr 7Co 2Ge 4 via a single ferromagnetic transition at 19 K. Spin-polarized electronic structure calculations for Pr 7Co 2Ge 4 reveal strong spin-orbit coupling within Pr and considerable magnetic contributions from Co atoms. This work suggests that similar structural chemistry can emerge for other rare earth-late transition metal-main group systems.« less

Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep

PubMed Central

Chianini, Francesca; Cosseddu, Gian Mario; Steele, Philip; Hamilton, Scott; Hawthorn, Jeremy; Síso, Sílvia; Pang, Yvonne; Finlayson, Jeanie; Eaton, Samantha L.; Reid, Hugh W.; Dagleish, Mark P.; Di Bari, Michele Angelo; D’Agostino, Claudia; Agrimi, Umberto; Terry, Linda; Nonno, Romolo

2015-01-01

The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools. The data may help to optimise strategies to prevent exposure of humans to small ruminant TSE material via the food chain. Abnormal PrP distribution/accumulation was assessed by immunohistochemistry (IHC), Western blot (WB) and ELISA in samples from four animals. In addition, infectivity was detected using a sensitive bank vole bioassay with selected samples from two of the four sheep and protein misfolding cyclic amplification using bank vole brain as substrate (vPMCA) was also carried out in selected samples from one animal. Lymph nodes, oculomotor muscles, sciatic nerve and kidney were positive by IHC, WB and ELISA, although at levels 100–1000 fold lower than the brain, and contained detectable infectivity by bioassay. Tissues not infectious by bioassay were also negative by all laboratory tests including PMCA. Although discrepancies were observed in tissues with very low levels of abnormal PrP, there was an overall good correlation between IHC, WB, ELISA and bioassay results. Most importantly, there was a good correlation between the detection of abnormal PrP in tissues using laboratory tests and the levels of infectivity even when the titre was low. These findings provide useful information for risk modellers and represent a first step toward the validation of laboratory tests used to quantify prion infectivity, which would greatly aid TSE risk assessment policies. PMID:25807559

Parental Communication, Engagement, and Support During the Adolescent Voluntary Medical Male Circumcision Experience.

PubMed

Dam, Kim H; Kaufman, Michelle R; Patel, Eshan U; Van Lith, Lynn M; Hatzold, Karin; Marcell, Arik V; Mavhu, Webster; Kahabuka, Catherine; Mahlasela, Lusanda; Njeuhmeli, Emmanuel; Seifert Ahanda, Kim; Ncube, Getrude; Lija, Gissenge; Bonnecwe, Collen; Tobian, Aaron A R

2018-04-03

Voluntary medical male circumcision (VMMC) is one of few opportunities in sub-Saharan Africa to engage male adolescents in the healthcare system. Limited data are available on the level of parental communication, engagement, and support adolescents receive during the VMMC experience. We conducted 24 focus group discussions with parents/guardians of adolescents (N = 192) who agreed to be circumcised or were recently circumcised in South Africa, Tanzania, and Zimbabwe. In addition, male adolescents (N = 1293) in South Africa (n = 299), Tanzania (n = 498), and Zimbabwe (n = 496) were interviewed about their VMMC experience within 7-10 days postprocedure. We estimated adjusted prevalence ratios (aPRs) using multivariable Poisson regression with generalized estimating equations and robust standard errors. Parents/guardians noted challenges and gaps in communicating with their sons about VMMC, especially when they did not accompany them to the clinic. Adolescents aged 10-14 years were significantly more likely than 15- to 19-year-olds to report that their parent accompanied them to a preprocedure counseling session (56.5% vs 12.5%; P < .001). Among adolescents, younger age (aPR, 0.86; 95% confidence interval [CI], .76-.99) and rural setting (aPR, 0.34; 95% CI, .13-.89) were less likely to be associated with parental-adolescent communication barriers, while lower socioeconomic status (aPR, 1.37; 95% CI, 1.00-1.87), being agnostic (or of a nondominant religion; aPR, 2.87; 95% CI, 2.21-3.72), and living in South Africa (aPR, 2.63; 95% CI, 1.29-4.73) were associated with greater perceived barriers to parental-adolescent communication about VMMC. Parents/guardians found it more difficult to be involved in wound care for older adolescents than for adolescents <15 years of age. Parents play a vital role in the VMMC experience, especially for younger male adolescents. Strategies are needed to inform parents completely throughout the VMMC adolescent experience, whether or not they accompany their sons to clinics.

Improving Pulse Rate Measurements during Random Motion Using a Wearable Multichannel Reflectance Photoplethysmograph.

PubMed

Warren, Kristen M; Harvey, Joshua R; Chon, Ki H; Mendelson, Yitzhak

2016-03-07

Photoplethysmographic (PPG) waveforms are used to acquire pulse rate (PR) measurements from pulsatile arterial blood volume. PPG waveforms are highly susceptible to motion artifacts (MA), limiting the implementation of PR measurements in mobile physiological monitoring devices. Previous studies have shown that multichannel photoplethysmograms can successfully acquire diverse signal information during simple, repetitive motion, leading to differences in motion tolerance across channels. In this paper, we investigate the performance of a custom-built multichannel forehead-mounted photoplethysmographic sensor under a variety of intense motion artifacts. We introduce an advanced multichannel template-matching algorithm that chooses the channel with the least motion artifact to calculate PR for each time instant. We show that for a wide variety of random motion, channels respond differently to motion artifacts, and the multichannel estimate outperforms single-channel estimates in terms of motion tolerance, signal quality, and PR errors. We have acquired 31 data sets consisting of PPG waveforms corrupted by random motion and show that the accuracy of PR measurements achieved was increased by up to 2.7 bpm when the multichannel-switching algorithm was compared to individual channels. The percentage of PR measurements with error ≤ 5 bpm during motion increased by 18.9% when the multichannel switching algorithm was compared to the mean PR from all channels. Moreover, our algorithm enables automatic selection of the best signal fidelity channel at each time point among the multichannel PPG data.

Unraveling HIV protease flaps dynamics by Constant pH Molecular Dynamics simulations.

PubMed

Soares, Rosemberg O; Torres, Pedro H M; da Silva, Manuela L; Pascutti, Pedro G

2016-08-01

The active site of HIV protease (HIV-PR) is covered by two flaps. These flaps are known to be essential for the catalytic activity of the HIV-PR, but their exact conformations at the different stages of the enzymatic pathway remain subject to debate. Understanding the correct functional dynamics of the flaps might aid the development of new HIV-PR inhibitors. It is known that, the HIV-PR catalytic efficiency is pH-dependent, likely due to the influence of processes such as charge transfer and protonation/deprotonation of ionizable residues. Several Molecular Dynamics (MD) simulations have reported information about the HIV-PR flaps. However, in MD simulations the protonation of a residue is fixed and thus it is not possible to study the correlation between conformation and protonation state. To address this shortcoming, this work attempts to capture, through Constant pH Molecular Dynamics (CpHMD), the conformations of the apo, substrate-bound and inhibitor-bound HIV-PR, which differ drastically in their flap arrangements. The results show that the HIV-PR flaps conformations are defined by the protonation of the catalytic residues Asp25/Asp25' and that these residues are sensitive to pH changes. This study suggests that the catalytic aspartates can modulate the opening of the active site and substrate binding. Copyright © 2016 Elsevier Inc. All rights reserved.

Prion propagation in cells expressing PrP glycosylation mutants.

PubMed

Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Crystal Structure and Properties of Imidazo-Pyridine Ionic Liquids.

PubMed

Farren-Dai, Marco; Cameron, Stanley; Johnson, Michel B; Ghandi, Khashayar

2018-07-05

Computational studies were performed on novel protic ionic liquids imidazolium-[1,2-a]-pyridine trifluoroacetate [ImPr][TFA] synthesized by the reaction of imidazo-[1,2a]-pyridine (ImPr) with trifluoroacetic acid (TFA), and on fused salt imidazolium-[1,2-a]-pyridine maleamic carbonate [ImPr][Mal] synthesized by reaction of ImPr with maleamic acid (Mal). Synthesis was performed as one-pot reactions, which applies green chemistry tenets. Both these compounds begin to decompose at 180°C. Our computational studies suggest another thermal reaction channel, in which [ImPr][Mal] can also thermally polymerizes to polyacrylamide which then cyclizes. This is thermal product remains stable up to 700 degrees, consistent with our thermogravimetric studies. [ImPr][TFA] exhibited good conductivity and ideal ionic behavior, as evaluated by a Walden plot. X-ray crystallography of [ImPr][TFA] revealed a tightly packed system for the crystals as a result of strong ionic interaction, pi-stacking, and fluorine-CH interactions. Both synthesized compounds exhibited some CO 2 absorptivity, with [ImPr][Mal] outperforming [ImPr][TFA] in this regard. The quantum chemistry based computational methods can shed light on many properties of these ionic liquids, but they are challenged in fully describing their ionic nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Self-Consent for HIV Prevention Research Involving Sexual and Gender Minority Youth: Reducing Barriers Through Evidence-Based Ethics.

PubMed

Fisher, Celia B; Arbeit, Miriam R; Dumont, Melissa S; Macapagal, Kathryn; Mustanski, Brian

2016-02-01

This project examined the attitudes of sexual and gender minority youth (SGMY) toward guardian permission for a pre-exposure prophylaxis (PrEP) adherence trial and their preparedness to provide informed, rational, and voluntary self-consent. Sixty sexually active SGMY (ages 14-17) participated in online survey and asynchronous focus group questions after watching a video describing a PrEP adherence study. Youth responses highlighted guardian permission as a significant barrier to research participation, especially for those not "out" to families. Youth demonstrated understanding of research benefits, medical side effects, confidentiality risks, and random assignment and felt comfortable asking questions and declining participation. Reasoning about participation indicated consideration of health risks and benefits, personal sexual behavior, ability to take pills every day, logistics, and post-trial access to PrEP. Results demonstrate youth's ability to self-consent to age- and population-appropriate procedures, and underscore the value of empirical studies for informing institutional review board (IRB) protections of SGMY research participants. © The Author(s) 2016.

Self-Consent for HIV Prevention Research Involving Sexual and Gender Minority Youth: Reducing Barriers through Evidence-based Ethics

PubMed Central

Fisher, Celia B.; Arbeit, Miriam R.; Dumont, Melissa S.; Macapagal, Kathryn; Mustanski, Brian

2016-01-01

This project examined the attitudes of sexual and gender minority youth (SGMY) toward guardian permission for a pre-exposure prophylaxis (PrEP) adherence trial and their preparedness to provide informed, rational and voluntary self-consent. Sixty sexually active SGMY (ages 14–17) participated in online survey and asynchronous focus group questions after watching a video describing a PrEP adherence study. Youth responses highlighted guardian permission as a significant barrier to research participation, especially for those not “out” to families. Youth demonstrated understanding of research benefits, medical side effects, confidentiality risks, and random assignment and felt comfortable asking questions and declining participation. Reasoning about participation indicated consideration of health risks and benefits, personal sexual behavior, ability to take pills everyday, logistics, and post-trial access to PrEP. Results demonstrate youth’s ability to self-consent to age- and population- appropriate procedures, and underscore the value of empirical studies for informing IRB protections of SGMY research participants. PMID:26956988

TRMM Observations of Polarization Difference in 85 GHz: Information About Hydrometeors and Rain Rate

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.; Einaudi, Franco (Technical Monitor)

2000-01-01

Observations made by the Precipitation Radar (PR) and the Microwave Imager (TMI) radiometer on board the Tropical Rainfall Measuring Mission (TRMM) satellite help us to show the significance of the 85 GHz polarization difference, PD85, measured by TMI. Rain type, convective or stratiform, deduced from the PR allows us to infer that PD85 is generally positive in stratiform rain clouds, while PD85 can be markedly negative in deep convective rain clouds. Furthermore, PD85 increases in a gross manner as stratiform rain rate increases. On the contrary, in a crude fashion PD85 decreases as convective rain rate increases. From the observations of TMI and PR, we find that PD85 is a weak indicator of rain rate. Utilizing information from existing polarimetric radar studies, we infer that negative values of PD85 are likely associated with vertically-oriented small oblate or wet hail that are found in deep convective updrafts.

A multimedia Electronic Patient Record (ePR) system for Image-Assisted Minimally Invasive Spinal Surgery

PubMed Central

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, HK

2009-01-01

Purpose This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on Image-Assisted Minimally Invasive Spinal Surgery as a clinical application. Methods Three clinical Phases of Minimally Invasive Spinal Surgery workflow in Pre-Op, Intra-Op, and Post Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a Minimally Invasive Spinal Surgery clinical site with user training and support for daily use. Summary A step-by step approach was introduced to develop a multi-media ePR system for Imaging-Assisted Minimally Invasive Spinal Surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed. PMID:20033507

Development of an Instrument for Assessing the Effectiveness of Chemistry Classroom Teaching

NASA Astrophysics Data System (ADS)

Zheng, Changlong; Fu, Lihai; He, Peng

2014-04-01

Classroom teaching is a main frontier of the implementation of new curricular ideas in China. The study reported in this article is concerned with the effectiveness of system of classroom teaching (SCT) in chemistry lessons. According to the Systems Science theory, we took a macroscopic view on the SCT, arguing that SCT is a hierarchy of system, which includes class system, plate system, unit system, and primitive system. In this study, we focused on primitive system of classroom teaching (PrS)—the lowest level in a SCT. Using focus group interviews, this study investigated the variables related to the effectiveness of PrS. We found a total of 21 such variables. To identify the main factors underlying the effectiveness of PrS, we further used exploratory factor analysis and confirmatory factor analysis. We found five main factors: rational use of time, quality of teaching behavior chain, match degree, quality of using resource and technology, and rationality of primitive content. Based on these findings, we constructed an evaluation scale for assessing the effectiveness of primitive system of chemistry classroom teaching.

ESO PR Highlights in 2006

NASA Astrophysics Data System (ADS)

2007-01-01

Last year proved to be another exceptional year for the European organisation for ground-based astronomy. ESO should begin the New Year with two new member states: Spain (PR 05/06) and the Czech Republic (PR 52/06). ESO PR Highlights 2006 2006 was a year of renovation and revolution in the world of planets. A new Earth-like exoplanet has been discovered (PR 03/06) using a network of telescopes from all over the world (including the Danish 1.54-m one at ESO La Silla). It is not the only child of this fruitful year: thanks to the combined use of ESO's Very Large Telescope (VLT) and La Silla instruments, a surprising system of twin giant exoplanets was found (PR 29/06), and a trio of Neptune-like planets hosted by a nearby star were identified (PR 18/06). These results open new perspectives on the search for habitable zones and on the understanding of the mechanism of planet formation. The VISIR instrument on the VLT has been providing unique information to answer this last question, by supplying a high resolution view of a planet-forming disc (PR 36/06). There are not only new members in the planets' register: during the General Assembly of the International Astronomical Union held in Prague (Czech Republic), it was decided that Pluto is not a planet anymore but a 'dwarf planet'. Whatever its status, Pluto still has a satellite, Charon, whose radius and density have been measured more accurately by observing a rare occultation from different sites, including Cerro Paranal (PR 02/06). The scientific community dedicated 2006 to the great physicist James Clerk Maxwell (it was the 175th anniversary of the birth): without his electromagnetic theory of light, none of the astonishing discoveries of modern physics could have been achieved. Nowadays we can look at distant galaxies in great detail: the GIRAFFE spectrograph on the VLT revealed that galaxies 6 billion years ago had the same amount of dark matter relative to stars than nowadays (PR 10/06), while SINFONI gave an unprecedented detailed map of a proto-disc galaxy, showing how galaxies looked like 10 billion years ago (PR 31/06). The VLT also helped to discover a large primordial (more than 10 billion years away) 'blob', explained as the early stage formation of a galaxy (PR 23/06). Not only far away galaxies are rich of surprises: also our own Galaxy was the object of investigations during 2006 and its history is now less obscure (PR 34/06 and 41/06). ESO's Very Large Telescope unveiled that the stellar cluster Messier 12 must have lost to our Milky Way galaxy close to one million low-mass stars (PR 04/06). Stealing is not uncommon in astronomy: evidence of stellar vampires - star sucking off material from another - was unearthed in the globular cluster 47 Tucanae (PR 37/06). Still closer to home, the VLT observed Schwassmann-Wachmann 3, a comet that is breaking apart and revealed many mini-comets (PR 15/06). At Paranal, a fourth Auxiliary Telescope was installed for the Very Large Telescope Interferometer (PR 51/06), and since January 2006, not only do natural stars shine: the first artificial star twinkles in the Southern Hemisphere. It does not guide the sailors (it is too faint to be seen by the unaided eye), but it conducts the eye of the present and future telescopes (PR 07/06). And 2006 proved an important year for the future project of ESO, the Extremely Large Telescope. After approval from the ESO council, the European community can now start the final design of this telescope that will without doubt revolutionise astronomy (PR 25/06 and 46/06). ESO PR Photos 2006 2006 was without doubt an explosive year: the explosion of a supernovae of Type Ia in the enchanting Hooked Galaxy was followed from the middle of 2005 for more than a year (PR 22/06) and using observations of 17 supernovae Ia astronomers could make light on the nature of such explosions, that are likely to occur at supersonic speed (PR 44/06). Supernovae are proved to be linked to X-ray flashes (PR 33/06) and to the more energetic gamma-ray bursts. But not all the explosions are associated with supernovae, and a new kind of explosion is indeed suggested by the observation of a new mysterious category of gamma-ray bursts (PR 49/06). The Atacama Pathfinder Experiment (APEX) 12-m sub-millimetre telescope lived up to the ambitions of the scientists by providing access to the 'Cold Universe' with unprecedented sensitivity and image quality. As a demonstration, no less than 26 articles based on early science with APEX were published in a special issue of the research journal Astronomy & Astrophysics (PR 24/06). This year ESO and Chile celebrated ten years of collaboration: a cooperation that led not only to breakthrough discoveries, but also to a growth of astronomy and related sciences in the South American country (PR 21/06). ESO published many images last year as well, including two huge ones, made with the Wide Field Imager: one, made of about 300 million pixels, shows an 'empty field' (PR 14/06), while the other, a 256 million pixel mosaic, depicts in amazing detail the Tarantula Nebula (PR 50/06). These and other images can be accessed through the clickable map, including amazing images of galaxies and of a finally identified flying object (PR 48/06).

Community member perspectives from transgender women and men who have sex with men on pre-exposure prophylaxis as an HIV prevention strategy: implications for implementation

PubMed Central

2012-01-01

Background An international randomized clinical trial (RCT) on pre-exposure prophylaxis (PrEP) as an human immunodeficiency virus (HIV)-prevention intervention found that taken on a daily basis, PrEP was safe and effective among men who have sex with men (MSM) and male-to-female transgender women. Within the context of the HIV epidemic in the United States (US), MSM and transgender women are the most appropriate groups to target for PrEP implementation at the population level; however, their perspectives on evidenced-based biomedical research and the results of this large trial remain virtually unknown. In this study, we examined the acceptability of individual daily use of PrEP and assessed potential barriers to community uptake. Methods We conducted semi-structured interviews with an ethnoracially diverse sample of thirty HIV-negative and unknown status MSM (n = 24) and transgender women (n = 6) in three California metropolitan areas. Given the burden of disease among ethnoracial minorities in the US, we purposefully oversampled for these groups. Thematic coding and analysis of data was conducted utilizing an approach rooted in grounded theory. Results While participants expressed general interest in PrEP availability, results demonstrate: a lack of community awareness and confusion about PrEP; reservations about PrEP utilization, even when informed of efficacious RCT results; and concerns regarding equity and the manner in which a PrEP intervention could be packaged and marketed in their communities. Conclusions In order to effectively reduce HIV health disparities at the population level, PrEP implementation must take into account the uptake concerns of those groups who would actually access and use this biomedical intervention as a prevention strategy. Recommendations addressing these concerns are provided. PMID:23181780

Hypothalamic S1P/S1PR1 axis controls energy homeostasis.

PubMed

Silva, Vagner R R; Micheletti, Thayana O; Pimentel, Gustavo D; Katashima, Carlos K; Lenhare, Luciene; Morari, Joseane; Mendes, Maria Carolina S; Razolli, Daniela S; Rocha, Guilherme Z; de Souza, Claudio T; Ryu, Dongryeol; Prada, Patrícia O; Velloso, Lício A; Carvalheira, José B C; Pauli, José Rodrigo; Cintra, Dennys E; Ropelle, Eduardo R

2014-09-25

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

RadNet Air Data From San Juan, PR

EPA Pesticide Factsheets

This page presents radiation air monitoring and air filter analysis data for San Juan, PR from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

PrAS: Prediction of amidation sites using multiple feature extraction.

PubMed

Wang, Tong; Zheng, Wei; Wuyun, Qiqige; Wu, Zhenfeng; Ruan, Jishou; Hu, Gang; Gao, Jianzhao

2017-02-01

Amidation plays an important role in a variety of pathological processes and serious diseases like neural dysfunction and hypertension. However, identification of protein amidation sites through traditional experimental methods is time consuming and expensive. In this paper, we proposed a novel predictor for Prediction of Amidation Sites (PrAS), which is the first software package for academic users. The method incorporated four representative feature types, which are position-based features, physicochemical and biochemical properties features, predicted structure-based features and evolutionary information features. A novel feature selection method, positive contribution feature selection was proposed to optimize features. PrAS achieved AUC of 0.96, accuracy of 92.1%, sensitivity of 81.2%, specificity of 94.9% and MCC of 0.76 on the independent test set. PrAS is freely available at https://sourceforge.net/p/praspkg. Copyright © 2016 Elsevier Ltd. All rights reserved.

Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression.

PubMed

Pinto, Rita; Hansen, Lars; Hintze, John; Almeida, Raquel; Larsen, Sylvester; Coskun, Mehmet; Davidsen, Johanne; Mitchelmore, Cathy; David, Leonor; Troelsen, Jesper Thorvald; Bennett, Eric Paul

2017-07-27

Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide a strategy for characterization of dose-dependent effector functions of essential genes that require absence of endogenous gene expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pulmonary Rehabilitation in Ontario: A Cross-Sectional Survey

PubMed Central

Bowen, James M; Campbell, Kaitryn; Sutherland, Simone; Bartlett, Ann; Brooks, Dina; Qureshi, Riaz; Goldstein, Roger; Gershon, Andrea S; Prevost, Shelley; Samis, Lorelei; Kaplan, Alan G; Hopkins, Robert B; MacDougald, Craig; Nunes, Erica; O'Reilly, Daria J; Goeree, Ron

2015-01-01

Background Pulmonary rehabilitation (PR) is a comprehensive intervention of exercise training, education, and behaviour change to improve the physical and psychological condition of people with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and to promote long-term adherence to health-enhancing behaviours. Although PR is considered the standard of care for patients with COPD who remain symptomatic despite bronchodilator therapies, current evidence suggests that only 1.15% of COPD patients across Canada have access to PR facilities for care. Objectives The objectives of this study were to identify the number of health care facilities across Ontario providing PR services for patients with COPD, describe the scope of those services, and determine the province's current capacity to provide PR services relative to need, for the province as a whole and by local health integration network (LHIN). Methods The Pulmonary Rehabilitation Programs in Ontario (PRO) Survey was a province-wide, descriptive, cross-sectional survey of health care facilities (hospitals, family health teams, and community health centres). It was distributed to 409 facilities to collect information on various aspects of PR services in the province. Results Between April 2013 and February 2014, 187 facilities responded to the survey (46% response rate). Most responding centres (144) did not offer PR services, and only 43 were full PR sites providing a comprehensive program. Hospital-based programs made up the majority of sites offering full PR services (67%), followed by programs based at family health teams (19%) and community health centres (14%). More than 90% of PR programs are outpatient-based. The average wait time for outpatient PR was 6.9 weeks, and 58% of programs provide services 5 days per week. More than 80% of patients attending PR complete the full program. Across all program types, the total estimated provincial capacity for PR outpatient care is 4,524 patients per year, or 0.66% to 1.78% of patients with COPD, depending on the estimated prevalence of disease. Limitations These results are representative of 12 of the 14 LHINs in Ontario due to low response rates in facilities in 2 LHINs. Conclusions Although some increase in capacity has occurred since a similar survey in 2005, PR resources in Ontario are insufficient to support the delivery of care to people with COPD in accordance with clinical practice guideline recommendations. PMID:26366242

On the lower bound of monitor solutions of maximally permissive supervisors for a subclass α-S3PR of flexible manufacturing systems

NASA Astrophysics Data System (ADS)

Chao, Daniel Yuh

2015-01-01

Recently, a novel and computationally efficient method - based on a vector covering approach - to design optimal control places and an iteration approach that computes the reachability graph to obtain a maximally permissive liveness enforcing supervisor for FMS (flexible manufacturing systems) have been reported. However, it is unclear as to the relationship between the structure of the net and the minimal number of monitors required. This paper develops a theory to show that the minimal number of monitors required cannot be less than that of basic siphons in α-S3PR (systems of simple sequential processes with resources). This confirms that two of the three controlled systems by Chen et al. are of a minimal monitor configuration since they belong to α-S3PR and their number in each example equals that of basic siphons.

Explaining the Efficacy of Pre-exposure Prophylaxis (PrEP) for HIV Prevention: A Qualitative Study of Message Framing and Messaging Preferences Among US Men Who have Sex with Men.

PubMed

Underhill, Kristen; Morrow, Kathleen M; Colleran, Christopher; Calabrese, Sarah K; Operario, Don; Salovey, Peter; Mayer, Kenneth H

2016-07-01

We investigated message comprehension and message framing preferences for communicating about PrEP efficacy with US MSM. We conducted eight focus groups (n = 38) and n = 56 individual interviews with MSM in Providence, RI. Facilitators probed comprehension, credibility, and acceptability of efficacy messages, including percentages, non-numerical paraphrases, efficacy ranges versus point estimates, and success- versus failure-framed messages. Our findings indicated a range of comprehension and operational understandings of efficacy messages. Participants tended to prefer percentage-based and success-framed messages, although preferences varied for communicating about efficacy using a single percentage versus a range. Participants reported uncertainty about how to interpret numerical estimates, and many questioned whether trial results would predict personal effectiveness. These results suggest that providers and researchers implementing PrEP may face challenges in communicating with users about efficacy. Efforts to educate MSM about PrEP should incorporate percentage-based information, and message framing decisions may influence message credibility and overall PrEP acceptability.

[Determinants of maternal near miss in an obstetric intensive care unit].

PubMed

De Souza, Maria Aparecida Cardoso; De Souza, Tházio Henrique Soares Cardoso; Gonçalves, Ana Katherine Da Silveira

2015-11-01

To evaluate the risk factors for morbidity and mortality in an obstetric intensive care unit at a university hospital. Observational cross-sectional study with 492 pregnant/puerperal women. Patients were admitted to the obstetric intensive care unit over a period of one year, being informed about the proposals of the study and a questionnaire was applied. The analysis was performed using Microsoft Excel 2013 and GraphPad Prism 6. To evaluate risk factors, χ2 tests were used. The main risk factors to near miss were: non-white race (OR=2.5; PR=2.3); marital status (married women) (OR=7.9; PR=7.1), schooling (primary) (OR=3.1; PR=2.8), being from the countryside (OR=4.6; PR=4.0), low income (OR=70; PR=5.5), gestational hypertensive disorders (OR=16.3; PR=13.2), receiving prenatal care (OR=5.0; PR=4.254) and C-section before labor (OR=39.2; PR=31.2). The prevalence of near miss was associated with socioeconomic/clinical factors and care issues, revealing the importance of interventions to improve these indicators. Additionally, we suggest a better curriculum insertion of this subject in the discipline of the medical course due to the importance of avoiding the near miss using adequate medical education. The importance of correct prenatal care is emphasized in order to identify potential risks, to provide nutritional support to pregnant women, to treat potential diseases and to establish a maternal immunization program, as well as providing better care regarding the clinical features of the patients, in order to reduce obstetrical and neonatal risk.

West Nile virus infectious replicon particles generated using a packaging-restricted cell line is a safe reporter system.

PubMed

Li, Wei; Ma, Le; Guo, Li-Ping; Wang, Xiao-Lei; Zhang, Jing-Wei; Bu, Zhi-Gao; Hua, Rong-Hong

2017-06-12

West Nile virus (WNV) is a neurotropic pathogen which causes zoonotic disease in humans. Recently, there have been an increasing number of infected cases and there are no clinically approved vaccines or effective drugs to treat WNV infections in humans. The purpose of this study was to facilitate vaccine and antiviral drug discovery by developing a packaging cell line-restricted WNV infectious replicon particle system. We constructed a DNA-based WNV replicon lacking the C-prM-E coding region and replaced it with a GFP coding sequence. To produce WNV replicon particles, cell lines stably-expressing prM-E and C-prM-E were constructed. When the WNV replicon plasmid was co-transfected with a WNV C-expressing plasmid into the prM-E-expressing cell line or directly transfected the C-prM-E expressing cell line, the replicon particle was able to replicate, form green fluorescence foci, and exhibit cytopathic plaques similar to that induced by the wild type virus. The infectious capacity of the replicon particles was restricted to the packaging cell line as the replicons demonstrated only one round of infection in other permissive cells. Thus, this system provides a safe and convenient reporter WNV manipulating tool which can be used to study WNV viral invasion mechanisms, neutralizing antibodies and antiviral efficacy.

PageRank and rank-reversal dependence on the damping factor

NASA Astrophysics Data System (ADS)

Son, S.-W.; Christensen, C.; Grassberger, P.; Paczuski, M.

2012-12-01

PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d0=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d0.

Acceptance of lean redesigns in primary care: A contextual analysis.

PubMed

Hung, Dorothy; Gray, Caroline; Martinez, Meghan; Schmittdiel, Julie; Harrison, Michael I

Lean is a leading change strategy used in health care to achieve short-term efficiency and quality improvement while promising longer-term system transformation. Most research examines Lean intervention to address isolated problems, rather than to achieve broader systemic changes to care delivery. Moreover, no studies examine contextual influences on system-wide Lean implementation efforts in primary care. The aim of this study was to identify contextual factors most critical to implementing and scaling Lean redesigns across all primary care clinics in a large, ambulatory care delivery system. Over 100 interviews and focus groups were conducted with frontline physicians, clinical staff, and operational leaders. Data analysis was guided by a modified Consolidated Framework for Implementation Research (CFIR), a popular implementation science framework. On the basis of expert recommendations, the modified framework targets factors influencing the implementation of process redesigns. This modified framework, the CFIR-PR, informed our identification of contextual factors that most impacted Lean acceptance among frontline physicians and staff. Several domains identified by the CFIR-PR were critical to acceptance of Lean redesigns. Regarding the implementation process acceptance was influenced by time and intensity of exposure to changes, "top-down" versus "bottom-up" implementation styles, and degrees of employee engagement in developing new workflows. Important factors in the inner setting were the clinic's culture and style of leadership, along with availability of information about Lean's effectiveness. Last, implementation efforts were impacted by individual and team characteristics regarding changed work roles and related issues of professional identity, authority, and autonomy. This study underscores the need for change leaders to consider the contextual factors that surround efforts to implement Lean in primary care. As Lean redesigns are scaled across a system, special attention is warranted with respect to the implementation approach, internal clinic setting, and implications for professional roles and identities of physicians and staff.

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.

PubMed

Di Biagio, Antonio; Riccardi, Niccolò; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

PubMed

Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

2017-07-01

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface.

PubMed

Salvesen, Ø; Reiten, M R; Espenes, A; Bakkebø, M K; Tranulis, M A; Ersdal, C

2017-05-22

The cellular prion protein (PrP C ) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrP C (PRNP Ter/Ter ) provides a novel model for studying PrP C physiology. In order to explore putative roles for PrP C in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter ) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrP C . In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with the immune response, such as ISG15, CXCL12, CXCL14, and acute phase proteins, among others. Activation of cytokine-responsive genes was skewed towards a more profound type I interferon response, and a less obvious type II response, in PrP C -deficient goats. The magnitude of gene expression in response to LPS was smaller in the hippocampus than in the choroid plexus. Resting state expression profiles revealed a few differences between the PRNP genotypes. Our data suggest that PrP C acts as a modulator of certain pathways of innate immunity signaling, particularly downstream of interferons, and probably contributes to protection of vulnerable tissues against inflammatory damage.

Goats without Prion Protein Display Enhanced Proinflammatory Pulmonary Signaling and Extracellular Matrix Remodeling upon Systemic Lipopolysaccharide Challenge.

PubMed

Salvesen, Øyvind; Reiten, Malin R; Kamstra, Jorke H; Bakkebø, Maren K; Espenes, Arild; Tranulis, Michael A; Ersdal, Cecilie

2017-01-01

A naturally occurring mutation in the PRNP gene of Norwegian dairy goats terminates synthesis of the cellular prion protein (PrP C ), rendering homozygous goats ( PRNP Ter/Ter ) devoid of the protein. Although PrP C has been extensively studied, particularly in the central nervous system, the biological role of PrP C remains incompletely understood. Here, we examined whether loss of PrP C affects the initial stage of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Acute pulmonary inflammation was induced by intravenous injection of LPS ( Escherichia coli O26:B6) in 16 goats (8 PRNP Ter/Ter and 8 PRNP +/+ ). A control group of 10 goats (5 PRNP Ter/Ter and 5 PRNP +/+ ) received sterile saline. Systemic LPS challenge induced sepsis-like clinical signs including tachypnea and respiratory distress. Microscopic examination of lungs revealed multifocal areas with alveolar hemorrhages, edema, neutrophil infiltration, and higher numbers of alveolar macrophages, with no significant differences between PRNP genotypes. A total of 432 ( PRNP +/+ ) and 596 ( PRNP Ter/Ter ) genes were differentially expressed compared with the saline control of the matching genotype. When assigned to gene ontology categories, biological processes involved in remodeling of the extracellular matrix (ECM), were exclusively enriched in PrP C -deficient goats. These genes included a range of collagen-encoding genes, and proteases such as matrix metalloproteinases ( MMP1, MMP2, MMP14, ADAM15 ) and cathepsins. Several proinflammatory upstream regulators (TNF-α, interleukin-1β, IFN-γ) showed increased activation scores in goats devoid of PrP C . In conclusion, LPS challenge induced marked alterations in the lung tissue transcriptome that corresponded with histopathological and clinical findings in both genotypes. The increased activation of upstream inflammatory regulators and enrichment of ECM components could reflect increased inflammation in the absence of PrP C . Further studies are required to elucidate whether these alterations may affect the later reparative phase of ALI.

Multiple pre- and post-analytical lean approaches to the improvement of the laboratory turnaround time in a large core laboratory.

PubMed

Lou, Amy H; Elnenaei, Manal O; Sadek, Irene; Thompson, Shauna; Crocker, Bryan D; Nassar, Bassam A

2017-10-01

Core laboratory (CL), as a new business model, facilitates consolidation and integration of laboratory services to enhance efficiency and reduce costs. This study evaluates the impact of total laboratory automation system (TLA), electric track vehicle (ETV) system and auto-verification (AV) of results on overall turnaround time (TAT) (phlebotomy to reporting TAT: PR-TAT) within a CL setting. Mean, median and percentage of outlier (OP) for PR-TAT were compared for pre- and post-CL eras using five representative tests based on different request priorities. Comparison studies were also carried out on the intra-laboratory TAT (in-lab to reporting TAT: IR-TAT) and the delivery TAT (phlebotomy to in-lab TAT: PI-TAT) to reflect the efficiency of the TLA (both before and after introducing result AV) and ETV systems respectively. Median PR-TATs for the urgent samples were reduced on average by 16% across all representative analytes. Median PR-TATs for the routine samples were curtailed by 51%, 50%, 49%, 34% and 22% for urea, potassium, thyroid stimulating hormone (TSH), complete blood count (CBC) and prothrombin time (PT) respectively. The shorter PR-TAT was attributed to a significant reduction of IR-TAT through the TLA. However, the median PI-TAT was delayed when the ETV was used. Application of various AV rules shortened the median IR-TATs for potassium and urea. However, the OP of PR-TAT for the STAT requests exceeding 60min were all higher than those from the pre-CL era. TLA and auto-verification rules help to efficiently manage substantial volumes of urgent and routine samples. However, the ETV application as it stands shows a negative impact on the PR-TAT. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Pressure ulcer prevention in long-term-care facilities: a pilot study implementing standardized nurse aide documentation and feedback reports.

PubMed

Horn, Susan D; Sharkey, Siobhan S; Hudak, Sandra; Gassaway, Julie; James, Roberta; Spector, William

2010-03-01

To design and facilitate implementation of practice-based evidence changes associated with decreases in pressure ulcer (PrU) development in long-term-care (LTC) facilities and promote these practices as part of routine care. Pre/post observational study. Frail older adult residents in 11 US LTC facilities. Project facilitators assisted frontline multidisciplinary teams (certified nurse aides [CNAs], nurses, and dietitians/dietary aides) to develop streamlined standardized CNA documentation and weekly reports to identify high-risk residents and to integrate clinical reports into day-to-day practice and clinical decision making. The program was called "Real-Time Optimal Care Plans for Nursing Home QI" (Real-Time). Prevalence of PrUs using Centers for Medicare & Medicaid Services (CMS) quality measures (QMs), number of in-house-acquired PrUs, and number and completeness of CNA documentation forms. Seven study LTC facilities that reported data to CMS experienced a combined 33% (SD, 36.1%) reduction in the CMS high-risk PrU QM in 18 months and reduction in newly occurring PrUs (number of ulcers in the fourth quarter of 2003: range, 2-19; and in the third quarter of 2005: range, 1-6). Five of these LTC facilities that fully implemented Real-Time experienced a combined 48.1% (SD, 23.4%) reduction in the CMS high-risk PrU QM. Ten facilities reduced by an average of 2 to 5 their number of CNA documentation forms; CNA weekly documentation completeness reached a consistent level of 90% to 95%, and 8 facilities integrated the use of 2 to 4 weekly project reports in routine clinical decision making. Quality improvement efforts that provide access to focused and timely clinical information, facilitate change, and promote staff working together in multidisciplinary teams impacted clinical outcomes. Prevention of PrUs showed a trend of improvement in facilities that fully integrated tools to identify high-risk residents into day-to-day practice. CNA documentation facilitated better information for clinical decision making. More than 70 additional LTC facilities across the United States are implementing this QI program.

Pathogenesis-related proteins and peptides as promising tools for engineering plants with multiple stress tolerance.

PubMed

Ali, Sajad; Ganai, Bashir Ahmad; Kamili, Azra N; Bhat, Ajaz Ali; Mir, Zahoor Ahmad; Bhat, Javaid Akhter; Tyagi, Anshika; Islam, Sheikh Tajamul; Mushtaq, Muntazir; Yadav, Prashant; Rawat, Sandhya; Grover, Anita

Pathogenesis-related (PR) proteins and antimicrobial peptides (AMPs) are a group of diverse molecules that are induced by phytopathogens as well as defense related signaling molecules. They are the key components of plant innate immune system especially systemic acquired resistance (SAR), and are widely used as diagnostic molecular markers of defense signaling pathways. Although, PR proteins and peptides have been isolated much before but their biological function remains largely enigmatic despite the availability of new scientific tools. The earlier studies have demonstrated that PR genes provide enhanced resistance against both biotic and abiotic stresses, which make them one of the most promising candidates for developing multiple stress tolerant crop varieties. In this regard, plant genetic engineering technology is widely accepted as one of the most fascinating approach to develop the disease resistant transgenic crops using different antimicrobial genes like PR genes. Overexpression of PR genes (chitinase, glucanase, thaumatin, defensin and thionin) individually or in combination have greatly uplifted the level of defense response in plants against a wide range of pathogens. However, the detailed knowledge of signaling pathways that regulates the expression of these versatile proteins is critical for improving crop plants to multiple stresses, which is the future theme of plant stress biology. Hence, this review provides an overall overview on the PR proteins like their classification, role in multiple stresses (biotic and abiotic) as well as in various plant defense signaling cascades. We also highlight the success and snags of transgenic plants expressing PR proteins and peptides. Copyright © 2018 Elsevier GmbH. All rights reserved.

Cardiovascular risk factors among Russian, Somali and Kurdish migrants in comparison with the general Finnish population.

PubMed

Skogberg, Natalia; Laatikainen, Tiina; Koskinen, Seppo; Vartiainen, Erkki; Jula, Antti; Leiviskä, Jaana; Härkänen, Tommi; Koponen, Päivikki

2016-08-01

There is limited information on cardiovascular risk among migrants. We compared cardiovascular risk factors among three major migrant groups in Finland with the general population. Cross-sectional data from 30- to 64-year-old health examination participants (n = 921) of the Migrant Health and Wellbeing Study (2010-12) were used. Data for comparison with the general Finnish population were obtained from the Health 2011 Study (n = 892). Russian men had a similar risk profile to that of the reference group. Kurdish men had lower prevalence of hypertension [prevalence ratio (PR) 0.55, 95% confidence interval (CI) 0.39-0.79] but higher prevalence of dyslipidaemia (PR: 1.12, 95% CI: 1.02-1.24) and hyperglycaemia (PR: 2.61, 95% CI: 1.88-3.64) compared with the reference group. Somali men had lower prevalence of smoking (PR: 0.18, 95% CI: 0.08-0.44), hypertension (PR: 0.55, 95% CI: 0.32-0.97)) and obesity (PR: 0.35, 95% CI: 0.17-0.71) but higher prevalence of hyperglycaemia (PR: 2.59, 95% CI: 1.73-3.86) compared with the reference group. Similar patterns were observed for women, except for higher prevalence of hyperglycaemia among Russian women (PR: 1.95, 95% CI: 1.26-3.01) and obesity among Kurdish and Somali women (PR: 1.41, 95% CI: 1.15-1.72 and PR: 1.68, 95% CI: 1.40-2.03, respectively) compared with the reference group. All migrant women had significantly lower prevalence of smoking than the reference group. There were significant variations in cardiovascular risk profiles of Kurdish and Somali migrants compared with the general population. Differences in cardiovascular risk factors by migrant group need to be taken into account in planning and implementing health promotion strategies. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Little Brother Joins the Large Family

NASA Astrophysics Data System (ADS)

2006-12-01

On the night of 15 December 2006, the fourth and last-to-be-installed VLTI Auxiliary Telescope (AT4) obtained its 'First Light'. The first images demonstrate that AT4 will be able to deliver the excellent image quality already delivered by the first three ATs. It will soon join its siblings to perform routinely interferometric measurements. ESO PR Photo 51a/06 ESO PR Photo 51a/06 VLT Auxiliary Telescope The VLT is composed of four 8.2-m Unit Telescope (Antu, Kueyen, Melipal and Yepun). They have been progressively put into service together with a vast suite of the most advanced astronomical instruments and are operated every night in the year. Contrary to other large astronomical telescopes, the VLT was designed from the beginning with the use of interferometry as a major goal. The VLT Interferometer (VLTI) combines starlight captured by two or three 8.2- VLT Unit Telescopes, dramatically increasing the spatial resolution and showing fine details of a large variety of celestial objects. ESO PR Photo 51b/06 ESO PR Photo 51b/06 One AT Under the Sky However, most of the time the large telescopes are used for other research purposes. They are therefore only available for interferometric observations during a limited number of nights every year. Thus, in order to exploit the VLTI each night and to achieve the full potential of this unique setup, some other (smaller), dedicated telescopes were included into the overall VLT concept. These telescopes, known as the VLTI Auxiliary Telescopes (ATs), are mounted on tracks and can be placed at precisely defined "parking" observing positions on the observatory platform. From these positions, their light beams are fed into the same common focal point via a complex system of reflecting mirrors mounted in an underground system of tunnels. The Auxiliary Telescopes are real technological jewels. They are placed in ultra-compact enclosures, complete with all necessary electronics, an air conditioning system and cooling liquid for thermal control, compressed air for enclosure seals, a hydraulic plant for opening the dome shells, etc. Each AT is also fitted with a transporter that lifts the telescope and relocates it from one station to another. It moves around with its own housing on the top of Paranal, almost like a snail. The VLTI is arguably the world's most advanced optical device of this type. It has already demonstrated its powerful capabilities by addressing several key scientific issues, such as determining the size and the shape of a variety of stars (ESO PR 22/02, PR 14/03, PR 31/03, and PR 09/06), measuring distances to stars (ESO PR 25/04), probing the innermost regions of the proto-planetary discs around young stars (ESO PR 27/04 and PR 35/06) or making the first detection by infrared interferometry of an extragalactic object (ESO PR 17/03).

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

PubMed Central

Hoover, Clare E.; Davenport, Kristen A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.; Soto, Claudio; Zabel, Mark D.

2017-01-01

ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrPCWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state. PMID:28250130

Signal transduction in neurons: effects of cellular prion protein on fyn kinase and ERK1/2 kinase.

PubMed

Tomasi, Vittorio

2010-12-16

It has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. As PrPc is a secreted protein anchored to the outer surface membrane through a glycosylphosphatidylinositol (GPI) anchor (secPrP) and caveolin-1 is located in the inner leaflet of plasma membrane, there is a problem of how the two proteins can physically interact each other and transduce signals. By using the GST-fusion proteins system we observed that PrPc strongly interacts with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal region, but not with the caveolin-1 N-terminal region. In vitro binding experiments were also performed to define the site(s) of PrPc interacting with cav-1. The results are consistent with a participation of PrPc octapeptide repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar localization of PrPc was ascertained by co-immunoprecipitation, by co-localization after flotation in density gradients and by confocal microscopy analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11) expressing caveolin-1 at high levels. We observed that, after antibody-mediated cross-linking or copper treatment, PrPc was internalized probably into caveolae. We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events.

Algorithmes et architectures pour ordinateurs quantiques supraconducteurs

NASA Astrophysics Data System (ADS)

Blais, A.

2003-09-01

Algorithms and architectures for superconducting quantum computers Since its formulation, information theory was based, implicitly, on the laws of classical physics. Such a formulation is however incomplete because it does not take into account quantum reality. During the last twenty years, expansion of theory information to include quantum effects has known growing interest. The practical realization of a system for quantum data processing system, a quantum computer, presents however many challenges. In this book, we are interested in various aspects of these challenges. We start by presenting algorithmic concepts like optimization of quantum computations and geometric quantum computation. We then consider various designs and aspects of qubits based on Josephson junctions. In particular, an original approach to the interaction between superconducting qubits is presented. This approach is very general since it can be applied to various designs of qubits. Finally, we are interested in read-out of the superconductic flux qubits. The detector suggested here has the advantage that it is possible to uncouple it from the qubit when no measurement is in progress. Depuis sa formulation, la théorie de l'information a été basée, implicitement, sur les lois de la physique classique. Une telle formulation est toutefois incomplète puisqu'elle ne tient pas compte de la réalité quantique. Au cours des vingt dernières années, l'expansion de la théorie de l'information, de façon à englober les effets purement quantiques, a connu un intérêt grandissant. La réalisation d'un système de traitement de l'information quantique, un ordinateur quantique, présente toutefois de nombreux défis. Dans cet ouvrage, on s'intéresse à différents aspects concernant ces défis. On commence par présenter des concepts algorithmiques comme l'optimisation de calculs quantiques et le calcul quantique géométrique. Par la suite, on s'intéresse à différents designs et aspects de l'utilisation de qubits basés sur les jonctions Josephson. On présente entre autres une approche originale pour l'interaction entre qubits. Cette approche est très générale puisqu'elle peut être appliquée à différents designs de qubits. Finalement, on s'intéresse à la lecture des qubits supraconducteurs de flux. Le détecteur suggéré ici a l'avantage de pouvoir être découplé du qubit lorsqu'il n'y a pas de mesure en cours.

Press and Community Relations. School Board Library Series, Volume 4.

ERIC Educational Resources Information Center

Kanige, Jeffrey; Ritterbusch, Peg

In response to the public's demand for information, school boards are advised to develop a properly managed and executed public information and community relations program. Goals of such a public relations (PR) program are outlined as: honesty in the dissemination of information, an organization oriented toward community involvement, and…

Retrieving the polarization information for satellite-to-ground light communication

NASA Astrophysics Data System (ADS)

Tao, Qiangqiang; Guo, Zhongyi; Xu, Qiang; Jiao, Weiyan; Wang, Xinshun; Qu, Shiliang; Gao, Jun

2015-08-01

In this paper, we have investigated the reconstruction of the polarization states (degree of polarization (DoP) and angle of polarization (AoP)) of the incident light which passed through a 10 km atmospheric medium between the satellite and the Earth. Here, we proposed a more practical atmospheric model in which the 10 km atmospheric medium is divided into ten layers to be appropriate for the Monte Carlo simulation algorithm. Based on this model, the polarization retrieve (PR) method can be used for reconstructing the initial polarization information effectively, and the simulated results demonstrate that the mean errors of the retrieved DoP and AoP are very close to zero. Moreover, the results also show that although the atmospheric medium system is fixed, the Mueller matrices for the downlink and uplink are completely different, which shows that the light transmissions in the two links are irreversible in the layered atmospheric medium system.

NRMRL/TTSD CUSTOMER SATISFACTION FOCUS GROUP

EPA Science Inventory

TTB uses a variety of technology transfer products and tools to communicate risk and information about technologies and research. TTB has begun a project to use EPA's generic Customer Satisfaction Survey Information Collection Request (ICR) to determine satisfaction with their pr...

Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study.

PubMed

Ware, Norma C; Pisarski, Emily E; Haberer, Jessica E; Wyatt, Monique A; Tumwesigye, Elioda; Baeten, Jared M; Celum, Connie L; Bangsberg, David R

2015-05-01

Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.

Muscle Signaling in Exercise Intolerance: Insights from the McArdle Mouse Model.

PubMed

Fiuza-Luces, Carmen; Nogales-Gadea, Gisela; García-Consuegra, Inés; Pareja-Galeano, Helios; Rufián-Vázquez, Laura; Pérez, Laura M; Andreu, Antoni L; Arenas, Joaquín; Martín, Miguel Angel; Pinós, Tomàs; Lucia, Alejandro; Morán, María

2016-08-01

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of the McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of "exercise intolerance," is to compare the skeletal muscle tissue of McArdle, heterozygous, and healthy (wild-type [wt]) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n = 4), p.R50X/wt (n = 6), and wt/wt mice (n = 5) (all male, 8 wk old) molecular markers of energy-sensing pathways, oxidative phosphorylation and autophagy/proteasome systems, oxidative damage, and sarcoplasmic reticulum Ca handling. We found a significant group effect for total adenosine monophosphate-(AMP)-activated protein kinase (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P = 0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice versus the other two groups. The absence of a massive accumulation of ubiquitinated proteins, autophagosomes, or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice versus the other two groups (P = 0.036), but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P = 0.011). Sarco(endo)plasmic reticulum ATPase 1 levels detected at 110 kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P = 0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated sarco(endo)plasmic reticulum ATPase 1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in oxidative phosphorylation capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

Dynamic compressive behavior of Pr-Nd alloy at high strain rates and temperatures

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

Wang Huanran; Cai Canyuan; Chen Danian

2012-07-01

Based on compressive tests, static on 810 material test system and dynamic on the first compressive loading in split Hopkinson pressure bar (SHPB) tests for Pr-Nd alloy cylinder specimens at high strain rates and temperatures, this study determined a J-C type [G. R. Johnson and W. H. Cook, in Proceedings of Seventh International Symposium on Ballistics (The Hague, The Netherlands, 1983), pp. 541-547] compressive constitutive equation of Pr-Nd alloy. It was recorded by a high speed camera that the Pr-Nd alloy cylinder specimens fractured during the first compressive loading in SHPB tests at high strain rates and temperatures. From highmore » speed camera images, the critical strains of the dynamic shearing instability for Pr-Nd alloy in SHPB tests were determined, which were consistent with that estimated by using Batra and Wei's dynamic shearing instability criterion [R. C. Batra and Z. G. Wei, Int. J. Impact Eng. 34, 448 (2007)] and the determined compressive constitutive equation of Pr-Nd alloy. The transmitted and reflected pulses of SHPB tests for Pr-Nd alloy cylinder specimens computed with the determined compressive constitutive equation of Pr-Nd alloy and Batra and Wei's dynamic shearing instability criterion could be consistent with the experimental data. The fractured Pr-Nd alloy cylinder specimens of compressive tests were investigated by using 3D supper depth digital microscope and scanning electron microscope.« less

Towards a fair consideration of PrEP as part of combination HIV prevention in Latin America

PubMed Central

Ravasi, Giovanni; Grinsztejn, Beatriz; Baruch, Ricardo; Guanira, Juan Vicente; Luque, Ricardo; Cáceres, Carlos F; Ghidinelli, Massimo

2016-01-01

Introduction Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. Discussion Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. Conclusions PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost-effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full-scale PrEP programmes. PMID:27760687

Towards a fair consideration of PrEP as part of combination HIV prevention in Latin America.

PubMed

Ravasi, Giovanni; Grinsztejn, Beatriz; Baruch, Ricardo; Guanira, Juan Vicente; Luque, Ricardo; Cáceres, Carlos F; Ghidinelli, Massimo

2016-01-01

Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost-effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full-scale PrEP programmes.

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

PubMed

Hannaford, Alisse; Lipshie-Williams, Madeleine; Starrels, Joanna L; Arnsten, Julia H; Rizzuto, Jessica; Cohen, Phillip; Jacobs, Damon; Patel, Viraj V

2018-04-01

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

Engineering Human Immunodeficiency Virus 1 Protease Heterodimers as Macromolecular Inhibitors of Viral Maturation

NASA Astrophysics Data System (ADS)

McPhee, Fiona; Good, Andrew C.; Kuntz, Irwin D.; Craik, Charles S.

1996-10-01

Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection.

Effects of pulmonary rehabilitation in bronchiectasis: A retrospective study.

PubMed

Ong, H K; Lee, A L; Hill, C J; Holland, A E; Denehy, L

2011-01-01

There is limited information about the benefits of pulmonary rehabilitation (PR) in patients with bronchiectasis. This study aimed to evaluate the effects of an out-patient PR program in patients with a primary diagnosis of bronchiectasis and to compare them with a matched COPD group who completed the same PR program. A retrospective review was conducted of patients with bronchiectasis or COPD who completed 6 to 8 weeks of PR at two tertiary institutions. The outcome measures were the 6-minute walk distance (6MWD) and Chronic Respiratory Disease Questionnaire (CRQ). Ninety-five patients with bronchiectasis completed the PR (48 male; FEV(1) 63 [24] % predicted; age 67 [10] years). Significant improvements in 6MWD (mean change 53.4 m, 95% CI 45.0 to 61.7) and CRQ total score (mean change 14.0 units, 95% CI 11.3 to 16.7) were observed immediately following PR. In patients with complete follow-up (n = 37), these improvements remained significantly higher than baseline at 12 months (20.5 m, 95% CI 1.4 to 39.5 for 6MWD; 12.1 points, 95% CI 5.7 to 18.4 for CRQ total score). The time trend and changes in the 6MWD and CRQ scores were not significantly different between the bronchiectasis and the COPD groups (all p > 0.05). This study supports the inclusion of patients with bronchiectasis in existing PR programs. Further prospective RCTs are warranted to substantiate these findings.

Spectroscopic investigations on Pr³+ and Nd³+ doped strontium-lithium-bismuth borate glasses.

PubMed

Rajesh, D; Balakrishna, A; Seshadri, M; Ratnakaram, Y C

2012-11-01

Spectroscopic investigations on different concentrations (0.1, 0.5, 1.0, 1.5 and 2.0mol%) of Pr(3+) and Nd(3+) doped strontium lithium bismuth borate glasses have been done. X-ray diffraction, SEM with EDS, absorption and luminescence spectra were recorded for all the glass matrices and analyzed. X-ray diffraction profiles and SEM images conformed amorphous nature of investigated glass samples. EDS spectra of host glass and Pr(3+)doped glass matrices gave information about the chemical composition of glass samples. From the absorption spectra of Pr(3+) and Nd(3+) ions, Judd-Ofelt (J-O) intensity parameters (Ω(λ),λ=2, 4 and 6) have been calculated and compared with other glass matrices. The emission characteristics such as radiative lifetimes (τ(R)), measured and calculated branching ratios (β) and stimulated emission cross-sections (σ(P)) have been obtained for the observed emission transitions of Pr(3+) and Nd(3+) ions in the above glass matrix for all the concentrations. From the emission spectra of Pr(3+) and Nd(3+) doped glass matrices, the effect of concentration on the quenching of intensity of (1)D(2)→(3)H(4) transition of Pr(3+) ion and (4)F(3/2)→(4)I(9/2), (4)I(11/2) and (4)I(13/2) transitions of Nd(3+) have been studied and discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model

PubMed Central

Fields, Peter D.; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

2017-01-01

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis. PMID:28222092

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

PubMed

Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

2017-02-01

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

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

Lin, Qisheng; Aguirre, Kaiser; Saunders, Scott M.

Planar hydrocarbon-like metal clusters may foster new insights linking organic molecules with conjugated π-π bonding interactions and inorganic structures in terms of their bonding characteristics. However, such clusters are uncommon in polar intermetallics. Herein, we report two polar intermetallic phases, Pr 5Co 2Ge 3 and Pr 7Co 2Ge 4, both of which feature such planar metal clusters, viz., ethylene-like [Co 2Ge 4] clusters plus the concatenated forms and polyacene-like [Co 2Ge 2] n ribbons in Pr 5Co 2Ge 3, and 1,2,4,5-tetramethylbenzene-like [Co4Ge6] cluster in Pr 7Co 2Ge 4. Just as in the related planar organic structures, these metal-metalloid species aremore » dominated by covalent bonding interactions. Both compounds magnetically order at low temperature with net ferromagnetic components: Pr 5Co 2Ge 3 via a series of transitions below 150 K; and Pr 7Co 2Ge 4 via a single ferromagnetic transition at 19 K. Spin-polarized electronic structure calculations for Pr 7Co 2Ge 4 reveal strong spin-orbit coupling within Pr and considerable magnetic contributions from Co atoms. This work suggests that similar structural chemistry can emerge for other rare earth-late transition metal-main group systems.« less

Photocopy of drawing (this photograph is an 8" x 10" ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing (this photograph is an 8" x 10" enlargement from a 4" x 5" negative; November 1993 revision of a November 10, 1973 as-built drawing by F. Marquez, in possession of the Highway System Administration Office of the Puerto Rico Highway and Transportation Authority). BRIDGE OVER HONDO RIVER ROUTE NO. 156 K.M. 28.9, COMERIO, P.R. - Puente Rio Hondo, Spanning Hondo River on PR Road 156, Barrio Rio Hondo, Comerio, Comerio Municipio, PR

Optical amplification at the 1. 31 wavelength

DOEpatents

Cockroft, N.J.

1994-02-15

An optical amplifier operating at the 1.31 [mu]m wavelength for use in such applications as telecommunications, cable television, and computer systems is described. An optical fiber or other waveguide device is doped with both Tm[sup 3+] and Pr[sup 3+] ions. When pumped by a diode laser operating at a wavelength of 785 nm, energy is transferred from the Tm[sup 3+] ions to the Pr[sup 3+] ions, causing the Pr[sup 3+] ions to amplify at a wavelength of 1.31. 1 figure.

Optical amplification at the 1.31 wavelength

DOEpatents

Cockroft, Nigel J.

1994-01-01

An optical amplifier operating at the 1.31 .mu.m wavelength for use in such applications as telecommunications, cable television, and computer systems. An optical fiber or other waveguide device is doped with both Tm.sup.3+ and Pr.sup.3+ ions. When pumped by a diode laser operating at a wavelength of 785 nm, energy is transferred from the Tm.sup.3+ ions to the Pr.sup.3+ ions, causing the Pr.sup.3+ ions to amplify at a wavelength of 1.31

Pr:YAlO(3) microchip laser.

PubMed

Fibrich, Martin; Jelínková, Helena; Sulc, Jan; Nejezchleb, Karel; Skoda, Václav

2010-08-01

A cw Pr:YAlO(3) microchip-laser operation in the near-IR spectral region is reported. A microchip resonator was formed by dielectric mirrors directly deposited on the Pr:YAlO(3) crystal surfaces. For active medium pumping, a GaN laser diode providing up to 1W of output power at approximately 448 nm was used. 139mW of laser radiation at 747nm wavelength has been extracted from the microchip-laser system. Slope efficiency related to the incident pumping power was approximately 25%.

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

USDA-ARS?s Scientific Manuscript database

Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

PubMed

Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

2013-12-01

We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

NASA Astrophysics Data System (ADS)

Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-03-01

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide information that will aid in the design of much improved HIV-1 PR antiviral drugs.

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa

PubMed Central

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R.; Bukusi, Elizabeth A.; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E.; Ware, Norma C.; Wyatt, Monique A.; Marzinke, Mark A.; Frenkel, Lisa M.; Celum, Connie; Baeten, Jared M.

2017-01-01

Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation. PMID:29355231

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa.

PubMed

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R; Bukusi, Elizabeth A; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E; Ware, Norma C; Wyatt, Monique A; Marzinke, Mark A; Frenkel, Lisa M; Celum, Connie; Baeten, Jared M

2017-11-06

Introduction : Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods : We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results : We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions : PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.

Predicting heat stress index in Sasso hens using automatic linear modeling and artificial neural network

NASA Astrophysics Data System (ADS)

Yakubu, A.; Oluremi, O. I. A.; Ekpo, E. I.

2018-03-01

There is an increasing use of robust analytical algorithms in the prediction of heat stress. The present investigation therefore, was carried out to forecast heat stress index (HSI) in Sasso laying hens. One hundred and sixty seven records on the thermo-physiological parameters of the birds were utilized. They were reared on deep litter and battery cage systems. Data were collected when the birds were 42- and 52-week of age. The independent variables fitted were housing system, age of birds, rectal temperature (RT), pulse rate (PR), and respiratory rate (RR). The response variable was HSI. Data were analyzed using automatic linear modeling (ALM) and artificial neural network (ANN) procedures. The ALM model building method involved Forward Stepwise using the F Statistic criterion. As regards ANN, multilayer perceptron (MLP) with back-propagation network was used. The ANN network was trained with 90% of the data set while 10% were dedicated to testing for model validation. RR and PR were the two parameters of utmost importance in the prediction of HSI. However, the fractional importance of RR was higher than that of PR in both ALM (0.947 versus 0.053) and ANN (0.677 versus 0.274) models. The two models also predicted HSI effectively with high degree of accuracy [r = 0.980, R 2 = 0.961, adjusted R 2 = 0.961, and RMSE = 0.05168 (ALM); r = 0.983, R 2 = 0.966; adjusted R 2 = 0.966, and RMSE = 0.04806 (ANN)]. The present information may be exploited in the development of a heat stress chart based largely on RR. This may aid detection of thermal discomfort in a poultry house under tropical and subtropical conditions.

Ethnogeological Cultural Model of Karst Derived from Traditional Knowledge in Puerto Rico and Dominican Republic

NASA Astrophysics Data System (ADS)

Garcia, A.; Semken, S. C.; Brandt, E.

2017-12-01

Ethnogeology is the scientific study of human relationships with and knowledge of the Earth system, and is typically investigated within the context of a specific culture. Many indigenous and local systems of environmental and place knowledge incorporate empirical observations and culturally framed interpretations of geological features and processes. Ethnogeological interpretations may differ from those of conventional mainstream geoscience, but they are validated by their direct relevance to long-term cultural and environmental resilience and sustainability, typically in challenging environments. Ethnogeologic findings can enrich geoscientific knowledge bases for further research, and inform place-based geoscience education that has been shown to engage and enrich students from diverse underrepresented minority backgrounds. Ethnogeological research blends methods from field geology with methods from field ethnography: such as participant observation, free listing, participatory mapping, and cultural consensus analysis among other methods from rapid participatory assessment. We report here on an ongoing field study in Puerto Rico (PR) and the Dominican Republic (DR) on ethnogeological knowledge of karst topography, geology, and hydrogeology among local cultural indigenous communities such as the Boricua jíbaro and the Dominican campesino. Applied focused ethnographic fieldwork results suggest a good fit for the cultural consensus model about geological processes among culturally expert consultants in DR (4.604) and PR (4.669), as well as competence average with values of 0.552 and 0.628 respectively. This suggests the existence of a regional cultural model for the domain of karst that is shared between PR and DR populations that reside in or near karst terrain. Additional data in support of the cultural model include stories, analogies, and family history using participant observation, and participatory mapping.

Predicting heat stress index in Sasso hens using automatic linear modeling and artificial neural network.

PubMed

Yakubu, A; Oluremi, O I A; Ekpo, E I

2018-03-17

There is an increasing use of robust analytical algorithms in the prediction of heat stress. The present investigation therefore, was carried out to forecast heat stress index (HSI) in Sasso laying hens. One hundred and sixty seven records on the thermo-physiological parameters of the birds were utilized. They were reared on deep litter and battery cage systems. Data were collected when the birds were 42- and 52-week of age. The independent variables fitted were housing system, age of birds, rectal temperature (RT), pulse rate (PR), and respiratory rate (RR). The response variable was HSI. Data were analyzed using automatic linear modeling (ALM) and artificial neural network (ANN) procedures. The ALM model building method involved Forward Stepwise using the F Statistic criterion. As regards ANN, multilayer perceptron (MLP) with back-propagation network was used. The ANN network was trained with 90% of the data set while 10% were dedicated to testing for model validation. RR and PR were the two parameters of utmost importance in the prediction of HSI. However, the fractional importance of RR was higher than that of PR in both ALM (0.947 versus 0.053) and ANN (0.677 versus 0.274) models. The two models also predicted HSI effectively with high degree of accuracy [r = 0.980, R 2  = 0.961, adjusted R 2  = 0.961, and RMSE = 0.05168 (ALM); r = 0.983, R 2  = 0.966; adjusted R 2  = 0.966, and RMSE = 0.04806 (ANN)]. The present information may be exploited in the development of a heat stress chart based largely on RR. This may aid detection of thermal discomfort in a poultry house under tropical and subtropical conditions.

Identification of Risk Factors for the Development of Pressure Ulcers Despite Standard Screening Methodology and Prophylaxis in Trauma Patients.

PubMed

Raff, Lauren A; Waller, Holly; Griffin, Russell L; Kerby, Jeffrey D; Bosarge, Patrick L

2016-07-01

To present information about a study of risk factors for development of pressure ulcers (PrUs) in trauma patients. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Describe the previous PrU research, scope of the problem, and methodology of the study.2. Explain the results of the study identifying PrU risk factors for trauma patients. Pressure ulceration prevention has been emphasized  over the past several years in inpatient hospital settings with  subsequent decreases in the development of pressure ulcers (PrUs).  However, there remains a subset of trauma and burn patients  that develop PrUs despite standard screening methodology and  prophylaxis. This study determines the conditions that predict  development of pressure ulcers (PrUs) despite conventional  prophylaxis and screening.  Demographic and PrU data were collected over a  5-year period from June 2008 to May 2013. Patients diagnosed  with PrUs upon arrival in the trauma bay were excluded from  analysis. An ordinal logistic regression of PrU stage was used to  estimate odds ratios (ORs) and associated 95% confidence intervals  (CIs) for the association between characteristics of interest and  odds of a PrU. A backward selection process was used to select the  most parsimonious model.  During the study period, 14,616 trauma patients were  admitted and had available data. A total of 124 patients (0.85%) that met inclusion criteria went on to develop PrUs during their hospital course. Factors associated with the development of PrUs included spine Abbreviated Injury Scale (AIS) >3 (OR, 5.72; CI, 3.63-9.01), mechanical ventilation (OR, 1.95; CI, 1.23-3.10) and age 40 to 64 (OR, 2.09; CI, 1.24-3.52) and age ≥ 65 (OR, 4.48; CI, 2.52-7.95). Interestingly, head injury AIS >3 was protective from the development of PrUs (OR, 0.56; CI, 0.32-0.96). Hypotension and shock defined as systolic BP <90 mm Hg and base deficit less than -6 were not associated with the development of PrUs. In addition, body mass index was not associated with PrU development.  Spinal injuries, older than age 40, and mechanical  ventilation predict the development of PrUs for a subset of  patients, despite conventional prophylaxis and screening. Advanced  prevention methods, such as low-air-loss mattresses for these patient  subgroups should be considered immediately upon identification  of these risk factors during the hospital course.

Seeking Augmented Information Content Concerning Diurnal Precipitation Achieved by Combining TRMM-PR and CloudSat-CPR Radar Data Sets

NASA Technical Reports Server (NTRS)

Smith, Eric A.; Kuo, Kwo-Sen; Carty, Hezekiah

2008-01-01

The CloudSat satellite's Cloud Profiling Radar (CPR) is a highly sensitive 94 GHz (W-band) nadir viewing radar system flown in retrograde sun synchronous orbit useful for determining the vertical structure of cloud hydrometeors down to sensitivity of approx. -30 dBZ reflectivity factor. Given this sensitivity, it is possible to unambiguously measure precipitation rates in clouds over a spectrum extending from approx. 0.08 - 3.0 mm hr (sup -1) down to altitudes of 0.5 km with approx.0.25 km vertical binning. This enables an effective means to measure a great deal of the drizzle and light rain spectrum. However, because of its near-polar sunsynchronous orbit, CloudSat cannot sample the diurnal cycle of precipitation, nor with its nadir-only CPR view can it obtain a high duty cycle in sampling precipitation at fixed local times over fixed positions. On the other hand, the TRMM satellite, which is flown in a non-sunsynchronous 35-degree inclined orbit carrying the 13.8 GHz KU-band Precipitation Radar (PR) scanning through nadir over an approx. 225 km swath, can sample both the diurnal cycle and with a much improved duty cycle relative to CloudSat. Moreover, the PR and CPR have the same 0.25 km vertical binning capability. The PR's greatest shortcoming is its approx. +17 dBZ sensitivity, which eliminates the possibility of measuring rain rates below -0.3-0.5 mm hr(sup -1), which can involve rainfall accumulations of up to 50% of the total over some regions. This begs the question of whether by combining CPR and PR data sets, whether it is possible to obtain an augmented measurement of the diurnal precipitation cycle. By collecting complimentary datasets during CloudSat and TRMM satellite orbit crossings within a delta t = 45-min proximity window, it is possible to demonstrate that whenever TRMM detects a precipitation signal, the correlations along the vertical axis between the reflectivities acquired from the CPR and PR are in inverse proportion to the magnitude of the delta t proximity window. By taking advantage of these underlying correlations, it is possible to develop a functional which can be used to broaden the reflectivity spectrum, concomitantly the rain rate spectrum, of the PR measurements based on the inherently broader reflectivity spectrum of the CPR at the lower reflectivity end of the spectrum, concomitantly at lighter rain rates. With the functional in place, it is then possible to produce synthetic CloudSat precipitation imagery over the PR track and thus over the diurnal time period. These augmented data are then used to study the spectral-vertical diurnal properties of precipitation over oceanic regions observed by TRMM.

Identification of novel putative-binding proteins for cellular prion protein and a specific interaction with the STIP1 homology and U-Box-containing protein 1

PubMed Central

Gimenez, Ana Paula Lappas; Richter, Larissa Morato Luciani; Atherino, Mariana Campos; Beirão, Breno Castello Branco; Fávaro, Celso; Costa, Michele Dietrich Moura; Zanata, Silvio Marques; Malnic, Bettina; Mercadante, Adriana Frohlich

2015-01-01

ABSTRACT Prion diseases involve the conversion of the endogenous cellular prion protein, PrPC, into a misfolded infectious isoform, PrPSc. Several functions have been attributed to PrPC, and its role has also been investigated in the olfactory system. PrPC is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp−/− mice showed impaired behavior in olfactory tests. Given the high PrPC expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrPC-binding partners. Ten different putative PrPC ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrPC with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrPC-Stub1 interaction are under investigation. The PrPC-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrPC is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein. PMID:26237451

Assessing the need for a pre-exposure prophylaxis programme using the social media app Grindr®.

PubMed

Hampel, B; Kusejko, K; Braun, D L; Harrison-Quintana, J; Kouyos, R; Fehr, J

2017-11-01

HIV pre-exposure prophylaxis (PrEP) is not approved in Switzerland and therefore must be paid for by the users themselves. We conducted a survey to find out whether men who have sex with men (MSM) in Switzerland are already taking PrEP, or are considering using it, and whether it is being taken under medical supervision or not. Grindr® is a geosocial networking app for MSM. Between 5 and 24 January 2017, users of the app who were located in Switzerland by a global positioning system (GPS) were asked to participate in a ten-question survey on PrEP use. Of the 2455 people who took part in the survey, 1893 were included in the analysis. Eighty-two participants (4.3%) reported that they were currently taking PrEP, 64 of whom (78%) said that they were under medical supervision. Seven PrEP users (9%) declared that they had not taken an HIV test within the previous 12 months. Nine hundred and forty-four (49.9%) were considering taking PrEP in the next 6 months, and 1474 (77.9%) were considering taking it at some point in the future. In an online survey carried out among sexually active MSM in Switzerland, only a minority of the individuals approached responded that they were currently using PrEP. However, the majority of participants were considering taking PrEP in the future. We identified a substantial proportion of PrEP users taking PrEP outside a medical setting. Hence, a national programme facilitating access to medical care and providing PrEP is urgently needed. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

PubMed

Velloza, Jennifer; Heffron, Renee

2017-10-01

This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina.

PubMed

Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

2015-07-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. Copyright © 2015 Elsevier Inc. All rights reserved.

Triggering N2 Uptake via Redox Induced Expulsion of Coordinated NH3 and N2 Silylation at Trigonal Bipyramidal Iron

PubMed Central

Lee, Yunho; Mankad, Neal P.

2010-01-01

The biological reduction of nitrogen to ammonia may occur via one of two predominant pathways in which nitrogenous NxHy intermediates including hydrazine (N2H4), diazene (N2H2), nitride (N3-) and imide (NH2-) may be involved. To test the validity of hypotheses concerning iron’s direct role in the stepwise reduction of N2, iron model systems are needed. Such systems can test the chemical compatibility of iron with various proposed NxHy intermediates, and the reactivity patterns of such species. Here we describe a TBP (SiPR3)Fe-L scaffold (SiPR3 represents [Si(o-C6H4PR2)3]−; R = Ph and iPr) where the apical site is occupied by nitrogenous ligands such as N2, N2H4, NH3 and N2R. The system accommodates terminally bound N2 in the three formal oxidation states (iron(0), +1, and +2). N2 uptake is demonstrated via displacement of its reduction partners NH3 and N2H4, and N2 functionalizaton is illustrated via electrophilic silylation. PMID:20571574

Patterns and Correlates of PrEP Drug Detection among MSM and Transgender Women in the Global iPrEx Study

PubMed Central

Liu, Albert; Glidden, David V.; Anderson, Peter L.; Amico, K.R.; McMahan, Vanessa; Mehrotra, Megha; Lama, Javier R.; MacRae, John; Hinojosa, Juan Carlos; Montoya, Orlando; Veloso, Valdilea G.; Schechter, Mauro; Kallas, Esper G.; Chariyalerstak, Suwat; Bekker, Linda-Gail; Mayer, Kenneth; Buchbinder, Susan; Grant, Robert

2014-01-01

Background Adherence to pre-exposure prophylaxis (PrEP) is critical for efficacy. Antiretroviral concentrations are an objective measure of PrEP use and correlate with efficacy. Understanding patterns and correlates of drug detection can identify populations at risk for non-adherence and inform design of PrEP adherence interventions. Methods Blood antiretroviral concentrations were assessed among active-arm participants in iPrEx, a randomized, placebo-controlled trial of emtricitabine/tenofovir in men who have sex with men (MSM) and transgender women in 6 countries. We evaluated rates and correlates of drug detection among a random sample of 470 participants at week 8 and a longitudinal cohort of 303 participants through 72 weeks of follow-up. Results Overall, 55% (95% CI 49–60%) of participants tested at week 8 had drug detected. Drug detection was associated with older age and varied by study site. In longitudinal analysis, 31% never had drug detected, 30% always had drug detected, and 39% had an inconsistent pattern. Overall detection rates declined over time. Drug detection at some or all visits was associated with older age; indices of sexual risk, including condomless receptive anal sex; and responding "don't know" to a question about belief of PrEP efficacy (0–10 scale). Conclusions Distinct patterns of study-product use were identified, with a significant proportion demonstrating no drug detection at any visit. Research literacy may explain greater drug detection among populations having greater research experience, such as older MSM in the US. Greater drug detection among those reporting highest-risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP. PMID:25230290

Non-daily pre-exposure prophylaxis for HIV prevention

PubMed Central

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Multiple Eyes for the VLT

NASA Astrophysics Data System (ADS)

2002-01-01

First System of Deployable Multi-Integral Field Units Ready Summary The ESO Very Large Telescope (VLT) at the Paranal Observatory is being equipped with many state-of-the-art astronomical instruments that will allow observations in a large number of different modes and wavebands. Soon to come is the Fibre Large Array Multi-Element Spectrograph (FLAMES) , a project co-ordinated by ESO. It incorporates several complex components, now being constructed at various research institutions in Europe and Australia. One of these, a true technological feat, is a unique system of 15 deployable fibre bundles, the so-called Integral Field Units (IFUs) . They can be accurately positioned within a sky field-of-view measuring no less that 25 arcmin in diameter, i.e., almost as large as the full Moon . Each of the IFUs looks like an insect's eye and images a small sky area (3 x 2 arcsec 2 ) with a multiple microlens. From each IFU, 20 narrow light beams are sent via optical fibres to an advanced spectrograph. All 300 spectra are recorded simultaneously by a sensitive digital camera. A major advantage of this technique is that, contrary usual spectroscopic observations in which spectral information is obtained along a (one-dimensional) line on the sky, it now allows (two-dimensional) area spectroscopy . This will permit extremely efficient spectral observations of many celestial objects, including faint galaxies, providing detailed information about their internal structure and motions. Such studies will have an important impact on our understanding, e.g., of the early evolution of galaxies , the main building blocks in the Universe. The IFUs have been developed by a team of astronomers and engineers [2] at the Observatoire de Paris-Meudon. All IFU components are now at the ESO Headquarters in Garching (Germany) where they are being checked and integrated into the instrument [3]. PR Photo 03a/02 : The GIRAFFE spectrograph in the ESO Assembly Hall (Garching, Germany) . PR Photo 03b/02 : Example of a future IFU observation in a sky field with galaxies. PR Photo 03c/02 : An illustration of how the IFUs function . PR Photo 03d/02 : The IFU design . PR Photo 03e/02 : Computer simulation of the motions in a galaxy , as deduced from IFU observations. The FLAMES instrument and its many parts ESO PR Photo 03a/02 ESO PR Photo 03a/02 [Preview - JPEG: 560 x 400 pix - 62k] [Normal - JPEG: 1120 x 800 pix - 544k] [Hi-Res - JPEG: 2885 x 2061 pix - 5.3M] Caption : PR Photo 03a/02 : The GIRAFFE spectrograph, a major component of the VLT Fibre Large Array Multi-Element Spectrograph (FLAMES) , during the present assembly at the ESO Headquarters in Garching (Germany). Late last year, the ESO Very Large Telescope (VLT) at the Paranal Observatory received its newest instrument, NAOS-CONICA . The first tests were very successful, cf. PR 25/01. But this is far from the last. Work is now underway at several European and overseas research institutes to complete the many other large astronomical instruments planned for the VLT. Over the next years, these new facilities will enter into operation one by one, further enhancing the capabilities of this true flagship of European science. One of these instruments is the Fibre Large Array Multi-Element Spectrograph (FLAMES) , to be installed at the 8.2-m VLT KUEYEN Unit Telescope. It will be able to observe the spectra of a large number of individual, faint objects (or small sky areas) simultaneously and incorporates several highly complex components, e.g., * a Nasmyth Corrector - an optical system to focus the light that is received from the telescope over a sky field of no less than 25 arcmin in diameter, i.e., almost as large as the full Moon . It was installed on KUEYEN in September 2001 * a Fibre Positioner (known as "OzPoz"). It is now being built by the AUSTRALIS Consortium, lead by the Anglo Australian Observatory (AAO) , cf. ESO PR 07/98 * a high- and intermediate-resolution optical spectrograph, GIRAFFE , with its own fibre system, developed by the Observatoire de Paris-Meudon in close collaboration with ESO . It is now in the process of being assembled in the ESO laboratories in Garching, cf. PR Photo 03a/01 . Work at the FLAMES facility will be supported by specialized data reduction software developed by Observatoire de Genève-Lausanne in collaboration with Observatoire de Paris-Meudon , and specialized observing software developed at ESO . There will also be a fibre link to the UVES high-dispersion spectrograph and there are plans for incorporating an intermediate resolution IR spectrograph in the future; the ITAL-FLAMES consortium is now preparing the associated instrument control and data reduction software packages. The Integral Field Units (IFUs) for FLAMES ESO PR Photo 03b/02 ESO PR Photo 03b/02 [Preview - JPEG: 573 x 400 pix - 94k] [Normal - JPEG: 1145 x 800 pix - 592k] ESO PR Photo 03c/02 ESO PR Photo 03c/02 [Preview - JPEG: 538 x 400 pix - 63k] [Normal - JPEG: 1076 x 800 pix - 256k] Caption : PR Photo 03b/02 : An example of observations with Integral Field Units (IFUs) at FLAMES (only 4 of the 15 units are shown here). Each IFU is placed so that it records the light from 20 small adjacent sky areas (each measuring about 3 x 2 arcsec 2 ). In this way, it is possible to register simultaneously the spectrum of as many different regions of a (distant) galaxy. PR Photo 03c/02 : How the IFUs work: each IFU consists of a microlens that guides the light from a small sky area, normally centred on a celestial object (e.g., a distant galaxy) and sends it on to the entry of the spectrograph (inside the dotted box). When it enters into operation later this year [3], GIRAFFE will become the most efficient instrument of its kind available at the world's large optical/infrared telescopes. It will be especially suited for the study of the dynamical properties of distant galaxies - their motion in space, as well as the internal motions of their stars and gas clouds. Indeed, observations of the velocity fields in a large variety of galaxies in the early Universe (when its age was only one third to one half of its current age) will be essential for a better understanding of those major building blocks of the Universe. This is first of all due to the unique system of 15 deployable fibre bundles, the Integral Field Units (IFUs) , that can be accurately positioned within a field-of-view measuring no less than 25 arcmin across, cf. PR Photo 03b/02 . Each IFU is a microscopic, state-of-the-art two-dimensional lens array with an aperture of 3 x 2 arcsec 2 on the sky. It contains twenty micro-lenses coupled with optical fibres leading the light recorded at each point in the field to the entry slit of the spectrograph, cf. PR Photo 03c/02 . A great advantage of this technique is that, contrary to usual spectroscopic observations in which spectral information is obtained along a (one-dimensional) line on the sky, it now allows (two-dimensional) area spectroscopy . It is therefore possible to obtain spectra of larger areas of a celestial object simultaneously, and not just along one particular diameter. With 15 IFUs at their disposal, the astronomers will be able to observe many galaxies at the same time - this will represent a tremendous gain of efficiency with many more astrophysical data collected within the available observation time! The IFU design ESO PR Photo 03d/02 ESO PR Photo 03d/02 [Preview - JPEG: 400 x 469 pix - 86k] [Normal - JPEG: 800 x 937 pix - 232k] Caption : PR Photo 03d/02 : Mechanical design of an IFU "button". Upper right: photo of an "IFU entrance" with the 20 square microlenses, each measuring 1.8 x 1.8 mm 2. PR Photo 03d/02 shows the mechanical design of the entrance of one IFU. An array of 20 square microlenses, each measuring 1.8 x 1.8 mm 2 is used to concentrate the light in the corresponding, small sky field onto a prism that passes the light on to 20 fibres. These are inserted and cemented into a mechanical holder and the entire assembly is then mounted in an IFU "button" that will be positioned in the focal plane by the OzPoz Positioner. A magnet is incorporated at the base of the button to ensure a stable position (a firm hold) on the focal plate during the observation. The optical cementing is ensured with an UV curing and the fibre bundle is cemented into the button with an epoxy glue in order to ensure excellent stiffness of the complete assembly. The external diameter of the button is about 6 mm, corresponding to about 11 arcsec on the sky, allowing quite close positioning of the buttons on the focal plate. An example of astronomical observations with IFUs ESO PR Photo 03e/02 ESO PR Photo 03e/02 [Preview - JPEG: 467 x 400 pix - 51k] [Normal - JPEG: 933 x 800 pix - 264k] Caption : PR Photo 03e/02 is a computer simulation of the velocity field in a galaxy , as deduced on the basis of IFU spectra. The blue area has negative velocities and is thus the approaching side of the galaxy, while the red area is receding. In this way, the direction of rotation can be determined. The velocity unit is km/s. During the astronomical observation with the IFUs , the spectrograph slit receives light from 15 sky areas simultaneously, each with 21 fibres (20 from the IFU and 1 that collects the light from the night sky in an adjacent sky field) or 22 fibres (with the addition of 1 fibre with light from a calibration lamp). Altogether, about 300 spectra are recorded simultaneously. By means of such observations, the astronomers can perform many different studies, e.g., of the dynamics of star clusters and motions of stars and interstellar clouds in galaxies. PR Photo 03e/02 provides an example of a computer simulation of a resulting diagramme in which the internal rotation of a distant spiral galaxy is clearly visible. Red and yellow areas have positive velocities that are approaching while the blue areas are receding). Of special interest will be the study of the often violent motions when two or more galaxies interact gravitationally. Notes [1]: This is a joint Press Release of ESO and the Observatoire de Paris (cf. http://www.obspm.fr/actual/nouvelle/jan02/flames.shtml ). [2]:The GIRAFFE team at the Observatoire de Paris that has developed the Integral Field Units (IFUs) discussed in this Press Release includes Jean-Pierre Aoustin, Sebastien Baratchart, Patrice Barroso, Veronique Cayatte, Laurent Chemin, Florence Cornu, Jean Cretenet, Jean-Paul Danton, Hector Flores, Francoise Gex, Fabien Guillon, Isabelle Guinouard, Francois Hammer, Jacques Hammes, David Horville, Jean-Michel Huet, Laurent Jocou, Pierre Kerlirzin, Serge Lebourg, Hugo Lenoir, Claude Lesqueren, Regis Marichal, Michel Marteaud, Thierry Melse, Fabrice Peltier, Francois Rigaud, Frederic Sayede and Pascal Vola . [3]: It is expected to ship the various components of the FLAMES instrument to the VLT Observatory at Paranal (Chile) during the next month. "First Light" is scheduled to take place some weeks thereafter, following installation at the telescope and extensive system tests. ESO will issue another Press Release with more details on that occasion.

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.

PubMed

Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A

2017-12-01

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

PubMed

Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

2016-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.

HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study.

PubMed

Colby, Donn; Srithanaviboonchai, Kriengkrai; Vanichseni, Suphak; Ongwandee, Sumet; Phanuphak, Nittaya; Martin, Michael; Choopanya, Kachit; Chariyalertsak, Suwat; van Griensven, Frits

2015-01-01

Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country. Thailand was one of the first countries in the world to successfully reverse a generalized HIV epidemic. Despite this early success, HIV prevalence has remained high among people who inject drugs and has surged among men who have sex with men (MSM) and transgender women (TGW). Two pivotal trials that showed that the use of oral antiretroviral medication as PrEP can reduce HIV transmission were conducted partially or entirely at Thai sites. Demonstration projects of PrEP, as well as clinical trials of alternative PrEP regimens, began or will begin in 2014-2015 in Thailand and will provide additional data and experience on how to best implement PrEP for high-risk individuals in the community. Financing of drug costs, the need for routine laboratory monitoring and lack of awareness about PrEP among at-risk groups all present challenges to the wider implementation of PrEP for HIV prevention in Thailand. Although significant challenges to wider use remain, PrEP holds promise as a safe and highly effective method to be used as part of a combined HIV prevention strategy for MSM and TGW in Thailand.

Expression of cellular prion protein in the frontal and occipital lobe in Alzheimer's disease, diffuse Lewy body disease, and in normal brain: an immunohistochemical study.

PubMed

Rezaie, Payam; Pontikis, Charlie C; Hudson, Lance; Cairns, Nigel J; Lantos, Peter L

2005-08-01

Cellular prion protein (PrP(c)) is a glycoprotein expressed at low to moderate levels within the nervous system. Recent studies suggest that PrP(c) may possess neuroprotective functions and that its expression is upregulated in certain neurodegenerative disorders. We investigated whether PrP(c) expression is altered in the frontal and occipital cortex in two well-characterized neurodegenerative disorders--Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)--compared with that in normal human brain using immunohistochemistry and computerized image analysis. The distribution of PrP(c) was further tested for correlation with glial reactivity. We found that PrP(c) was localized mainly in the gray matter (predominantly in neurons) and expressed at higher levels within the occipital cortex in the normal human brain. Image analysis revealed no significant variability in PrP(c) expression between DLBD and control cases. However, blood vessels within the white matter of DLBD cases showed immunoreactivity to PrP(c). By contrast, this protein was differentially expressed in the frontal and occipital cortex of AD cases; it was markedly overexpressed in the former and significantly reduced in the latter. Epitope specificity of antibodies appeared important when detecting PrP(c). The distribution of PrP(c) did not correlate with glial immunoreactivity. In conclusion, this study supports the proposal that regional changes in expression of PrP(c) may occur in certain neurodegenerative disorders such as AD, but not in other disorders such as DLBD.

78 FR 67979 - Hardwood Lumber and Hardwood Plywood Promotion, Research and Information Order; Referendum...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

...-11-0074; PR-B] RIN 0581-AD24 Hardwood Lumber and Hardwood Plywood Promotion, Research and Information... whether issuance of a proposed Hardwood Lumber and Hardwood Plywood Promotion, Research and Information... submitted on the Internet at: http://www.regulations.gov or to the Promotion and Economics Division, Fruit...

The informal use of antiretroviral medications for HIV prevention by men who have sex with men in South Florida: initiation, use practices, medications and motivations.

PubMed

Buttram, Mance E

2018-01-23

Limited data suggest that some gay and other men who have sex with men are using antiretroviral medications informally, without a prescription, for HIV prevention. This qualitative study examined this phenomenon among gay and other men who have sex with men in South Florida. Participants initiated informal antiretroviral medication use as a means of protecting each other and because of the confidence in knowledge of antiretroviral medications shared by their friends and sex partners. The most commonly used medications included Truvada and Stribild. Motivations for use included condom avoidance, risk reduction, and fear of recent HIV exposure. Participants described positive and negative sentiments related to informal use, including concerns about informal antiretroviral medications offering sufficient protection against HIV, and limited knowledge about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications used for PrEP have the potential to prevent HIV infection, future research must consider the informal antiretroviral medication use and related concerns, including adherence, diversion and viral resistance.

An economic evaluation of conception strategies for heterosexual serodiscordant couples where the male partner is HIV-positive.

PubMed

Letchumanan, Michelle; Coyte, Peter C; Loutfy, Mona

2015-01-01

To conduct an economic evaluation of the three commonly used interventions that reduce sexual HIV transmission when an HIV-negative female aims to conceive with an HIV-positive male on combination antiretroviral therapy (condomless sex restricted to timed ovulation [CS], sperm washing with intrauterine insemination [SW] and condomless sex restricted to timed ovulation with pre-exposure prophylaxis [CS-PrEP]). As SW and CS-PrEP are only privately available for pregnancy planning for this population in Canada, this study was conducted to inform policy decisions concerning potential public health insurance coverage, as well as to inform fertility counselling in settings with adequate combination antiretroviral therapy access globally. We developed a cohort Markov model with a lifetime horizon and used the perspective of Ontario's Ministry of Health (MOH). Input parameters were drawn from literature, the MOH's Schedule of Benefits and a time trade-off questionnaire designed for this study. Outcome measures included quality-adjusted life-years and incremental cost-effectiveness. Costs and benefits were discounted at annual rates of 3%. Costs were reported in Canadian 2013 dollars and an exchange rate of 1 USD to 1.066 CND was applied where necessary. Sensitivity analysis assessed the uncertainty of model parameters. The base case analysis found that CS-PrEP and SW were each more costly and less effective at conception than CS. The results were robust in the sensitivity analysis and suggest that CS is the dominant conception strategy in this population. Neither CS-PrEP nor SW represent better value for money relative to CS as a conception option for HIV-discordant couples with positive male partners. Based on these findings, CS-PrEP and SW cannot be recommended for public-funding in developed countries.

In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk.

PubMed

Selariu, Anca; Powers, Jenny G; Nalls, Amy; Brandhuber, Monica; Mayfield, Amber; Fullaway, Stephenie; Wyckoff, Christy A; Goldmann, Wilfred; Zabel, Mark M; Wild, Margaret A; Hoover, Edward A; Mathiason, Candace K

2015-11-01

The presence of disease-associated prions in tissues and bodily fluids of chronic wasting disease (CWD)-infected cervids has received much investigation, yet little is known about mother-to-offspring transmission of CWD. Our previous work demonstrated that mother-to-offspring transmission is efficient in an experimental setting. To address the question of relevance in a naturally exposed free-ranging population, we assessed maternal and fetal tissues derived from 19 elk dam-calf pairs collected from free-ranging Rocky Mountain elk from north-central Colorado, a known CWD endemic region. Conventional immunohistochemistry identified three of 19 CWD-positive dams, whereas a more sensitive assay [serial protein misfolding cyclic amplification (sPMCA)] detected CWD prion seeding activity (PrPCWD) in 15 of 19 dams. PrPCWD distribution in tissues was widespread, and included the central nervous system (CNS), lymphoreticular system, and reproductive, secretory, excretory and adipose tissues. Interestingly, five of 15 sPMCA-positive dams showed no evidence of PrPCWD in either CNS or lymphoreticular system, sites typically assessed in diagnosing CWD. Analysis of fetal tissues harvested from the 15 sPMCA-positive dams revealed PrPCWD in 80 % of fetuses (12 of 15), regardless of gestational stage. These findings demonstrated that PrPCWD is more abundant in peripheral tissues of CWD-exposed elk than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of CWD in naturally exposed cervid populations.

In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk

PubMed Central

Selariu, Anca; Powers, Jenny G.; Nalls, Amy; Brandhuber, Monica; Mayfield, Amber; Fullaway, Stephenie; Wyckoff, Christy A.; Goldmann, Wilfred; Zabel, Mark M.; Wild, Margaret A.; Hoover, Edward A.

2015-01-01

The presence of disease-associated prions in tissues and bodily fluids of chronic wasting disease (CWD)-infected cervids has received much investigation, yet little is known about mother-to-offspring transmission of CWD. Our previous work demonstrated that mother-to-offspring transmission is efficient in an experimental setting. To address the question of relevance in a naturally exposed free-ranging population, we assessed maternal and fetal tissues derived from 19 elk dam–calf pairs collected from free-ranging Rocky Mountain elk from north-central Colorado, a known CWD endemic region. Conventional immunohistochemistry identified three of 19 CWD-positive dams, whereas a more sensitive assay [serial protein misfolding cyclic amplification (sPMCA)] detected CWD prion seeding activity (PrPCWD) in 15 of 19 dams. PrPCWD distribution in tissues was widespread, and included the central nervous system (CNS), lymphoreticular system, and reproductive, secretory, excretory and adipose tissues. Interestingly, five of 15 sPMCA-positive dams showed no evidence of PrPCWD in either CNS or lymphoreticular system, sites typically assessed in diagnosing CWD. Analysis of fetal tissues harvested from the 15 sPMCA-positive dams revealed PrPCWD in 80 % of fetuses (12 of 15), regardless of gestational stage. These findings demonstrated that PrPCWD is more abundant in peripheral tissues of CWD-exposed elk than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of CWD in naturally exposed cervid populations. PMID:26358706

Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation.

PubMed Central

McPhee, F; Good, A C; Kuntz, I D; Craik, C S

1996-01-01

Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8876160

Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

PubMed Central

Bribián, Ana; Gavín, Rosalina; Reina, Manuel; García-Verdugo, José Manuel; Torres, Juan María; de Castro, Fernando; del Río, José Antonio

2012-01-01

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells. PMID:22529900

Close Vicinity of PrP Expressing Cells (FDC) with Noradrenergic Fibers in Healthy Sheep Spleen

PubMed Central

Lezmi, S.; Hunsmann, G.; Baron, T.

2001-01-01

In naturally and experimentally occurring scrapie in sheep, prions invade the immune system and replicate in lymphoid organs. Here we analysed immunohistochemically, in seven spleens of 6-month-old healthy sheep, the nature of the cells expressing prion protein (PrP) potentially supporting prion replication, as well as their relationship with autonomic innervation. PrP was identified using either RB1 rabbit antiserum or 4F2 monoclonal antibody directed against AA 108–123 portion of the bovine and AA 79–92 of human prion protein respectively. Using double labelling analysis, we demonstrated that PrPc is expressed by follicular dendritic cells using a specific monoclonal antibody (CNA42). We also showed the close vicinity of these PrP expressing cells with noradrenergic fibers, using a polyclonal tyrosine hydroxylase antibody. Our results may help the study of the cellular requirements for the possible neuroinvasion from the spleen. PMID:11785673

Thermoelectric power of PrMg3

NASA Astrophysics Data System (ADS)

Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

2010-01-01

PrMg3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg3.

Characterization and thermal behavior of PrMO{sub 3} (M = Co or Ni) ceramic materials obtained from gelatin

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

Aquino, F.M., E-mail: flavyma@hotmail.com; Melo, D.M.A.; Pimentel, P.M.

2012-09-15

Graphical abstract: The micrograph in figure shows sample calcined at temperature 900 °C. The sample exhibits morphology with considerable porosity and the formation of agglomerated nanometric particles. Gelatin provides the system with a large amount of organic matter, which is then removed during calcinations, favoring the appearance of pores in the material. Highlights: ► Oxides with PrNiO{sub 3} and PrCoO{sub 3} were prepared by new method synthesis. ► The gelatin, through its carboxylate groups and amine, is an efficient director. ► The obtained materials have magnetic properties and application in catalysis. ► The decomposition kinetic study of bonding groups ofmore » gelatin with metallic ions that takes part in the synthesis of PrMO{sub 3}. -- Abstract: Metal oxides with perovskite-type structure have attracted considerable interest in recent years due to their magnetic and electrical properties, as well as their catalytic activity. In this study, oxides with PrNiO{sub 3} and PrCoO{sub 3} composition were prepared by using gelatin powder as a precursor agent for its use as a catalyst. The powders obtained were calcined at 700 °C and 900 °C and characterized using the X-ray diffraction, thermal analysis (thermogravimetry and differential thermal analysis), infrared spectroscopy, temperature programed reduction and scanning electron microscopy techniques. Thermogravimetric data using the non-isothermal kinetic models of Flynn and Wall and “Model-free Kinetics” were used to determine the activation energy to study the decomposition kinetics of the ligand groups with system's metallic ions that takes part in the synthesis of PrMO{sub 3} (M = Ni or Co).« less

Formulation de cas dans la psychose débutante : Quels outils pour le travail en équipe?

PubMed Central

Elowe, Julien; Mebdouhi, Nadir; Solida, Alessandra; Conus, Philippe

2017-01-01

Nous présentons d’abord brièvement le programme TIPP et les concepts généraux de la prise en charge précoce dans la psychose débutante. Un des objectifs de l’intervention dans la phase précoce des troubles psychotiques est notamment de proposer des soins spécifiques adaptés à cette phase de la maladie. En début de prise en charge, l’équipe de soins et en particulier le gestionnaire de cas (case manager), chef d’orchestre de la prise en charge, sont confrontés à une quantité importante d’information dont il faut dégager les lignes de forces pour mettre en place une prise en charge adaptée. Cet article propose un modèle qui peut constituer un outil de travail précieux pour les équipes travaillant dans l’intervention précoce pour faire émerger une formulation de cas et synthétiser les situations cliniques des patients, en extraire une histoire qui fasse sens et ainsi faciliter la mise en place d’un projet thérapeutique. PMID:28558256

Modeling transport kinetics in clinoptilolite-phosphate rock systems

NASA Technical Reports Server (NTRS)

Allen, E. R.; Ming, D. W.; Hossner, L. R.; Henninger, D. L.

1995-01-01

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

Proteinase 3 Is a Phosphatidylserine-binding Protein That Affects the Production and Function of Microvesicles.

PubMed

Martin, Katherine R; Kantari-Mimoun, Chahrazade; Yin, Min; Pederzoli-Ribeil, Magali; Angelot-Delettre, Fanny; Ceroi, Adam; Grauffel, Cédric; Benhamou, Marc; Reuter, Nathalie; Saas, Philippe; Frachet, Philippe; Boulanger, Chantal M; Witko-Sarsat, Véronique

2016-05-13

Proteinase 3 (PR3), the autoantigen in granulomatosis with polyangiitis, is expressed at the plasma membrane of resting neutrophils, and this membrane expression increases during both activation and apoptosis. Using surface plasmon resonance and protein-lipid overlay assays, this study demonstrates that PR3 is a phosphatidylserine-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads. As phosphatidylserine is a major component of microvesicles (MVs), this study also examined the consequences of this interaction on MV production and function. PR3-expressing cells produced significantly fewer MVs during both activation and apoptosis, and this reduction was dependent on the ability of PR3 to associate with the membrane as mutating the hydrophobic patch restored MV production. Functionally, activation-evoked MVs from PR3-expressing cells induced a significantly larger respiratory burst in human neutrophils compared with control MVs. Conversely, MVs generated during apoptosis inhibited the basal respiratory burst in human neutrophils, and those generated from PR3-expressing cells hampered this inhibition. Given that membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis, MVs generated from neutrophils expressing membrane PR3 may potentiate oxidative damage of endothelial cells and promote the systemic inflammation observed in this disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteinase 3 Is a Phosphatidylserine-binding Protein That Affects the Production and Function of Microvesicles*

PubMed Central

Martin, Katherine R.; Kantari-Mimoun, Chahrazade; Yin, Min; Pederzoli-Ribeil, Magali; Angelot-Delettre, Fanny; Ceroi, Adam; Grauffel, Cédric; Benhamou, Marc; Reuter, Nathalie; Saas, Philippe; Frachet, Philippe; Boulanger, Chantal M.; Witko-Sarsat, Véronique

2016-01-01

Proteinase 3 (PR3), the autoantigen in granulomatosis with polyangiitis, is expressed at the plasma membrane of resting neutrophils, and this membrane expression increases during both activation and apoptosis. Using surface plasmon resonance and protein-lipid overlay assays, this study demonstrates that PR3 is a phosphatidylserine-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads. As phosphatidylserine is a major component of microvesicles (MVs), this study also examined the consequences of this interaction on MV production and function. PR3-expressing cells produced significantly fewer MVs during both activation and apoptosis, and this reduction was dependent on the ability of PR3 to associate with the membrane as mutating the hydrophobic patch restored MV production. Functionally, activation-evoked MVs from PR3-expressing cells induced a significantly larger respiratory burst in human neutrophils compared with control MVs. Conversely, MVs generated during apoptosis inhibited the basal respiratory burst in human neutrophils, and those generated from PR3-expressing cells hampered this inhibition. Given that membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis, MVs generated from neutrophils expressing membrane PR3 may potentiate oxidative damage of endothelial cells and promote the systemic inflammation observed in this disease. PMID:26961880

Evolution of structural, magnetic and transport behavior by Pr doping in SrRuO3

NASA Astrophysics Data System (ADS)

Gupta, Renu; Pramanik, A. K.

2018-05-01

Here we report the evolution of structural, magnetic and transport behavior in perovskite based ruthenates Sr1-xPrxRuO3 (x=0.0 and 0.1). The substitution of Pr on Sr site retains orthorhombic structure while we find the slight change in structural parameters. The SrRuO3 has itinerant ferromagnet (FM) type nature of ordering temperature ˜160 K and below the transition temperature showing large bifurcation between ZFC and FC magnetization. By Pr doping, the magnetic moment decreases with decreasing bifurcation of ZFC and FC. The ZFC data show three distinct peaks (three transition temperature; TM1,TM2 and TM3). The magnetization study of both the samples, at high temperature fitted with modified CWL showing the decreasing value of ordering temperature by Pr doping matches close to TM2. The low-temperature isothermal magnetization M (H) data show that the high field saturation moment has decreased by Pr doping. The Arrott plot gives spontaneous magnetization (Ms) which is also decreased by Pr substitution. Evolution of Rhodes-Wohlfarth ratio value increases, which suggests that FM in this system evolves toward the more itinerant type by Pr doping. The electrical resistivity ρ(T) of both the samples show metallic behavior, in the all temperature range and ρ(T) increases by Pr doping while around below 45 K, the resistivity decreases by Pr doping and this crossing temperature also matches with ZFC data.

Dancing around the Black Hole

NASA Astrophysics Data System (ADS)

2001-08-01

ISAAC Finds "Cool" Young Stellar Systems at the Centres of Active Galaxies Summary Supermassive Black Holes are present at the centres of many galaxies, some weighing hundreds of millions times more than the Sun. These extremely dense objects cannot be observed directly, but violently moving gas clouds and stars in their strong gravitational fields are responsible for the emission of energetic radiation from such "active galaxy nuclei" (AGN) . A heavy Black Hole feeds agressively on its surroundings . When the neighbouring gas and stars finally spiral into the Black Hole, a substantial fraction of the infalling mass is transformed into pure energy. However, it is not yet well understood how, long before this dramatic event takes place, all that material is moved from the outer regions of the galaxy towards the central region. So how is the food for the central Black Hole delivered to the table in the first place? To cast more light on this central question, a team of French and Swiss astronomers [1] has carried out a series of trailblazing observations with the VLT Infrared Spectrometer And Array Camera (ISAAC) on the VLT 8.2-m ANTU telescope at the ESO Paranal Observatory. The ISAAC instrument is particularly well suited to this type of observations. Visible light cannot penetrate the thick clouds of dust and gas in the innermost regions of active galaxies, but by recording the infrared light from the stars close to the Black Hole , their motions can be studied. By charting those motions in the central regions of three active galaxies (NGC 1097, NGC 1808 and NGC 5728), the astronomers were able to confirm the presence of "nuclear bars" in all three. These are dynamical structures that "open a road" for the flow of material towards the innermost region. Moreover, the team was surprised to discover signs of a young stellar population near the centres of these galaxies - stars that have apparently formed quite recently in a central gas disk. Such a system is unstable, however, and will soon disrupt. At some moment, many of those young stars may get too close to the monster in the centre and suffer an unhappy fate... PR Photo 25a/01 : The active galaxy NGC 1097 (R-band image) PR Photo 25b/01 : The active galaxy NGC 1808 (H-band image) PR Photo 25c/01 : The active galaxy NGC 5728 (K-band image) PR Photo 25d/01 : Schematic drawing of the various structural components mentioned in the text. PR Photo 25e/01 : ISAAC spectrum (2.3 µm) of the central region of NGC 1808 PR Photo 25f/01 : Stellar motions at the centre of NGC 1808 Central black holes in galaxies ESO PR Photo 25a/01 ESO PR Photo 25a/01 [Preview - JPEG: 400 x 489 pix - 39k] [Normal - JPEG: 800 x 977 pix - 296k] ESO PR Photo 25b/01 ESO PR Photo 25b/01 [Preview - JPEG: 400 x 499 pix - 40k] [Normal - JPEG: 800 x 997 pix - 168k] ESO PR Photo 25c/01 ESO PR Photo 25c/01 [Preview - JPEG: 400 x 488 pix - 47k] [Normal - JPEG: 800 x 975 pix - 384k] Caption : Photos of three active galaxies that were observed with ISAAC during the present programme. They show NGC 1097 (R-band; Photo 25a/01) and the central areas of NGC 1808 (H-band; Photo 25b/01) and NGC 5728 (K-band; Photo 25c/01). The bar-like structures and the luminous centres where the Black Holes are located are well visible - they are discussed in the text. The distances to these galaxies are approximately 55, 35 and 120 million light-years, respectively; the local scales are indicated in the photos. Technical information about these photos is available below. Recent research with space- and ground-based astronomical telescopes indicate that there are very heavy Black Holes at the centres of most galaxies. There is also general agreement among scientists that many of the closest neighbours of our own Milky Way Galaxy, for example the large spiral Andromeda Galaxy and the peculiar Centaurus A galaxy (cf. ESO PR 04/01 ), do contain central black holes with masses from millions to billions of solar masses [2]. Black Holes have an extremely intense gravitational field and as light can not escape from them, they are dark and invisible. Indeed, with presently available observational tools, they cannot be detected directly, only by effects resulting from interaction with their immediate surroundings. A small fraction of the black holes in galaxies are thus revealed by the spectacular activity they trigger in the central part of their hosts. Attracted by that heavy object, enormous quantities of gas (mostly hydrogen) spiral inwards towards the black hole. A disk-shaped structure forms in which the gas moves ever faster around the black hole while enormous amounts of energy are radiated at all wavelengths [3]. Getting the food to the Black Hole A great debate is now going on among scientists about how exactly the black holes are "fed". How is the gas first transported into the disk to fuel the seemingly insatiable supermassive black hole? It is still not well understood how the gas is moved from the outside to within a distance of 1000 light-years of the centre. Various violent processes have been mentioned in this context, like the merger of galaxies. A fine example of such an event was recently observed at the distant quasar HE 1013-2136 with the ESO Very Large Telescope, cf. ESO PR 13/01. The role of "nuclear bars" ESO PR Photo 25d/01 ESO PR Photo 25d/01 [Preview - JPEG: 364 x 400 pix - 89k] [Normal - JPEG: 727 x 800 pix - 264k] Caption : PR Photo 25d/01 is a schematic drawing of the various components of a double-barred galaxy, as mentioned in the text. Another possibility to move the gas inwards is the presence of bar-like structures at the centres of some galaxies, so-called "nuclear bars" . They look like small versions of the well-known, beautiful large-scale bar-like structures seen in galaxies like NGC 1365 (cf. ESO PR Photos 08a-e/99 ), but the responsible dynamical processes may possibly be somewhat different. Photo 25d/01 shows the various components that are discussed here in a schematic way. Acting as a gravitational brush, a bar that is thousands of light-years long efficiently "sweeps" the gas in that galaxy towards its core. When sufficient material has collected there, that matter may become dynamically "decoupled", forming a smaller bar at the centre of the larger "primary" bar. Such a "nuclear bar" may then, at least in theory, take over and let the gas move further inwards towards the central black hole. Until now, nuclear bars have mostly been seen on detailed images as small, elongated structures embedded within the larger primary bars - such structures may ressemble a "Russian doll". In addition, nuclear bars have been detected indirectly due to their gravitational effects, by means of very accurate measurements of the motions of the gas in the central region in a few galaxies. A first observational campaign by a team of French and Swiss astronomers [1] with the ESO Very Large Telescope (VLT) has now brought new, important insights about these nuclear bars. ISAAC spectra of the innermost regions of three active galaxies ESO PR Photo 25e/01 ESO PR Photo 25e/01 [Preview - JPEG: 400 x 424 pix - 40k] [Normal - JPEG: 800 x 847 pix - 256k] ESO PR Photo 25f/01 ESO PR Photo 25f/01 [Preview - JPEG: 400 x 241 pix - 40k] [Normal - JPEG: 800 x 401 pix - 112k] Caption : PR Photo 25e/01 is a reproduction of a long-slit ISAAC spectrum of the central region of the active galaxy NGC 1808 . It is in the 2.3 µm spectral region and the wavelength increases towards right. Several strong, vertical bands are seen; they are caused by CO-molecules in the atmospheres of the stars in this area. The bright band at the centre corresponds to the nucleus of the galaxy within which the central black hole is located. The characteristic S-shape is a result of the rotation of the stars around this centre, due to the Doppler effect. Technical information about this photo is available below. In the left half of PR Photo 25f/01 , the measured velocities (ordinate) of the stars near the centre of NGC 1808 are plotted at different distances from the nucleus (abscissa). The right half shows the corresponding curve after "removal" of the effect from the rotation - the remaining spread is a direct measure of the "velocity dispersion" and the individual stellar motions. As can be clearly seen, the width of the "band" decreases towards the centre, indicating the presence of a "dynamically cool" central stellar system. For more details, see the text. The scientists embarked upon a project with the goal of investigating in detail the motions of stars in the central regions of some active, comparatively "nearby" galaxies. As the innermost regions of such galaxies are usually quite dusty, the observations were carried out in infrared light that penetrates the dust clouds much better than does visible light. Thanks to its high efficiency and excellent imaging quality and spectral resolution, the VLT Infrared Spectrometer And Array Camera (ISAAC) is superbly suited for such work. Several galaxies with active centres were selected for the first observing runs in 1999 and 2000, among these NGC 1097, NGC 1808 and NGC 5728 that are shown in PR Photos 25a-c/01 . Infrared spectra were obtained in the 2.3 µm wavelength region in which a number of molecular spectral bands are seen, cf. PR Photo 25e/01 . They are caused by carbon monoxide ( 12 CO) molecules in the atmospheres of the stars located near the centres of the galaxies. Stellar motions By measuring the exact wavelengths of these molecular bands, it is possible to determine (from the Doppler effect), first, the mean velocity of the stars ( PR Photo 25f/01 ; left) and, secondly, the spread in this velocity (known as the "velocity dispersion" ; right). The first value reflects the general speed with which the stars move around the central black hole. The second indicates the extent to which the individual stellar motions deviate from that mean value. The comparison with the flight of a swarm of bees is useful: the mean velocity tells how fast the swarm moves forward as a whole - this is the ordered motion of the group. The second value instead indicates how much (or how fast) the individual bees move around inside the swarm - this is the spread in random velocities among the bees. Dynamical temperature is another concept defined by velocity dispersion. A warm gas is a gas where the molecules swarm around at high random speeds, while the molecules in a cold gas have low velocity dispersion. Astronomers often borrow this terminology and refer to stellar systems with low velocity dispersions as "dynamically cool systems". Confirming the "nuclear bars"... When "mapped" over the entire central area of a galaxy, these stellar velocity values provide detailed information about the gravitational field, and thus the mass distribution in the innermost region of the galaxy. The ISAAC observations did confirm the presence of "nuclear bars" in NGC 1097, NGC 1808 and NGC 5728. They also showed that these bars are truly "decoupled" stellar systems - their motions are only determined by the mass distribution in that area. ...and discovering a "dynamically cool" stellar system! However, the astronomers were very surprised to discover that in all three galaxies, the velocity dispersion is decreasing towards the centre, exactly contrary to what is predicted by simple models . The likely reason is the presence in the central region of a "newborn" system of stars whose individual velocities have not yet had time to "heat up". The project leader, Eric Emsellem explains: "Slower individual stellar motions correspond to a lower 'dynamical temperature' of the stellar system in this innermost region. We interpret this as evidence for a recent infall of gas that was induced by the nuclear bar. This has created a new gaseous disk at the centre of the galaxy, which has given birth to new stars. They all move around the black hole with more or less the same circular velocity as the gas from which they were born" . Agreement between observations and models This interesting scenario is supported by recent, extensive model computations by the team. In these computer models, large numbers of "stars" (mass points) move in a model galaxy with both a large and a nuclear bar, as observed in the three galaxies. Herve Wozniak refers to them as "self-consistent N-body simulations" and explains why the team is enthusiastic: "When our models also include star formation in the gas in the central region, a new, "dynamically cool" component of young stars emerges and mixes with the old stellar population" . He goes on: "The light from those young stars is superposed on that from the older ones in that area. Because of this, the overall "velocity dispersion" in the central region is then smaller than what it is further out. This is exactly as we observed in the ISAAC spectra obtained in the present programme" . Eric Emsellem points out that such a "dynamically cold" system is unstable and cannot last very long . "Soon it will "heat up" due to complex dynamical processes. It is quite possible that some of these stars will eventually end up as food for the hungry Black Hole.." Prospects With these new high-resolution infrared observations of the structure and the objects in the innermost regions of active galaxies, ISAAC and the VLT are paving the way for future studies of the processes that take place in the immediate neighbourhood of the central black holes. More active galaxies will now be observed with this method and it will be interesting to see if the presently discovered "cool" and young stellar systems represent a common phenomenon or not. More information The first stages of the research project reported in this Press Release are described in a scientific article ("Dynamics of embedded bars and the connection with AGN" by E. Emsellem et al.) that appeared in the European research journal Astronomy & Astrophysics (Vol. 368, p. 52). Two other articles about the new models and the implied properties of the central stellar population of young stars will follow. Notes [1]: The team consists of Eric Emsellem (Principal Investigator, Centre de Recherche Astronomique de Lyon, France), Didier Greusard and Daniel Friedli (Geneva Observatory, Switzerland), Francoise Combes (DEMIRM, Paris, France), Herve Wozniak (Marseille Observatory, France), Emmanuel Pecontal (Centre de Recherche Astronomique de Lyon, France) and Stephane Leon (University of Cologne, Germany). [2]: Black Holes represent an extreme physical phenomenon; if the Earth were to become one, it would measure no more than a few millimetres across. The gravitational field around a black hole is so intense that even light can not escape from it. [3]: On its most energetic and dramatic scale, this scenario results in a quasar , a type of object first discovered in 1963. In this case, the highly energetic centre of a galaxy completely outshines the outer structures and the "quasi-stellar object" appears star-like in smaller telescopes. Technical information about the photos PR Photo 25a/01 with NGC 1097 is a reproduction from the ESO LV archive, extracted via the Hypercat facility. It is based on a 2-hour photographic exposure in the R-band (Kodak IIIa-F emulsion + RG630 filtre) with the ESO 1-m Schmidt Telescope at La Silla and covers a field of about 35 x 35 arcmin 2. On this and the following photos, North is up and East is left. PR Photo 25b/01 of the central region of NGC 1808 was reproduced from an H-band (1.6 µm) image obtained with the IRAC2 camera (now decommissioned) at the MPG/ESO 2.2-m telescope on La Silla. The exposure time was 50 sec and the field measures 2.0 x 2.1 arcmin 2 (original pixel size = 0.52 arcsec). PR Photo 25c/01 of the central region of NGC 5728 was obtained at the 3.5-m Canada-France-Hawaii Telescope (CFHT) and the Adaptive-Optics PUEO instrument; the K-band (2.3 µm) exposure lasted 60 sec and the field measures 38 X 38 arcsec 2. PR Photo 25e/01 shows a raw, long-slit IR-spectrum in the 2.3 µm wavelength region, obtained with ISAAC along the major axis of this galaxy.

The promise and peril of pre-exposure prophylaxis (PrEP): using social science to inform prep interventions among female sex workers.

PubMed

Syvertsen, Jennifer L; Robertson Bazzi, Angela M; Scheibe, Andrew; Adebajo, Sylvia; Strathdee, Steffanie A; Wechsberg, Wendee M

2014-09-01

Advances in biomedical interventions to prevent HIV offer great promise in reducing the number of new infections across sub- Saharan Africa, particularly among vulnerable populations such as female sex workers. Several recent trials testing pre-exposure prophylaxis (PrEP) have demonstrated efficacy, although others have been stopped early for futility. Given the importance and complexities of social and behavioural factors that influence biomedical approaches to prevention, we discuss several key areas of consideration moving forward, including trial participation, adherence strategies, social relationships, and the structural factors that shape PrEP interest, use, and potential effectiveness among female sex workers in sub-Saharan Africa. Our review highlights the importance of involving social scientists in clinical and community-based research on PrEP. We advocate for a shift away from a singular "re-medicalization" of the HIV epidemic to that of a "reintegration" of interdisciplinary approaches to prevention that could benefit female sex workers and other key populations at risk of acquiring HIV.

A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts’ law style assessment procedure

PubMed Central

2014-01-01

Background Pattern recognition (PR) based strategies for the control of myoelectric upper limb prostheses are generally evaluated through offline classification accuracy, which is an admittedly useful metric, but insufficient to discuss functional performance in real time. Existing functional tests are extensive to set up and most fail to provide a challenging, objective framework to assess the strategy performance in real time. Methods Nine able-bodied and two amputee subjects gave informed consent and participated in the local Institutional Review Board approved study. We designed a two-dimensional target acquisition task, based on the principles of Fitts’ law for human motor control. Subjects were prompted to steer a cursor from the screen center of into a series of subsequently appearing targets of different difficulties. Three cursor control systems were tested, corresponding to three electromyography-based prosthetic control strategies: 1) amplitude-based direct control (the clinical standard of care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a concurrent activation of two degrees of freedom (DOF). We computed throughput (bits/second), path efficiency (%), reaction time (second), and overshoot (%)) and used general linear models to assess significant differences between the strategies for each metric. Results We validated the proposed methodology by achieving very high coefficients of determination for Fitts’ law. Both PR strategies significantly outperformed direct control in two-DOF targets and were more intuitive to operate. In one-DOF targets, the simultaneous approach was the least precise. The direct control was efficient in one-DOF targets but cumbersome to operate in two-DOF targets through a switch-depended sequential cursor control. Conclusions We designed a test, capable of comprehensively describing prosthetic control strategies in real time. When implemented on control subjects, the test was able to capture statistically significant differences (p < 0.05) in control strategies when considering throughputs, path efficiencies and reaction times. Of particular note, we found statistically significant (p < 0.01) improvements in throughputs and path efficiencies with simultaneous PR when compared to direct control or sequential PR. Amputees could readily achieve the task; however a limited number of subjects was tested and a statistical analysis was not performed with that population. PMID:24886664

A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts' law style assessment procedure.

PubMed

Wurth, Sophie M; Hargrove, Levi J

2014-05-30

Pattern recognition (PR) based strategies for the control of myoelectric upper limb prostheses are generally evaluated through offline classification accuracy, which is an admittedly useful metric, but insufficient to discuss functional performance in real time. Existing functional tests are extensive to set up and most fail to provide a challenging, objective framework to assess the strategy performance in real time. Nine able-bodied and two amputee subjects gave informed consent and participated in the local Institutional Review Board approved study. We designed a two-dimensional target acquisition task, based on the principles of Fitts' law for human motor control. Subjects were prompted to steer a cursor from the screen center of into a series of subsequently appearing targets of different difficulties. Three cursor control systems were tested, corresponding to three electromyography-based prosthetic control strategies: 1) amplitude-based direct control (the clinical standard of care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a concurrent activation of two degrees of freedom (DOF). We computed throughput (bits/second), path efficiency (%), reaction time (second), and overshoot (%)) and used general linear models to assess significant differences between the strategies for each metric. We validated the proposed methodology by achieving very high coefficients of determination for Fitts' law. Both PR strategies significantly outperformed direct control in two-DOF targets and were more intuitive to operate. In one-DOF targets, the simultaneous approach was the least precise. The direct control was efficient in one-DOF targets but cumbersome to operate in two-DOF targets through a switch-depended sequential cursor control. We designed a test, capable of comprehensively describing prosthetic control strategies in real time. When implemented on control subjects, the test was able to capture statistically significant differences (p < 0.05) in control strategies when considering throughputs, path efficiencies and reaction times. Of particular note, we found statistically significant (p < 0.01) improvements in throughputs and path efficiencies with simultaneous PR when compared to direct control or sequential PR. Amputees could readily achieve the task; however a limited number of subjects was tested and a statistical analysis was not performed with that population.

[Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition].

PubMed

Pita-Ramírez, L; Hurtado-Monroy, R; Labardini-Méndez, J

1992-01-01

A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura.

Role of nuclear progesterone receptor isoforms in uterine pathophysiology

PubMed Central

Patel, Bansari; Elguero, Sonia; Thakore, Suruchi; Dahoud, Wissam; Bedaiwy, Mohamed; Mesiano, Sam

2015-01-01

BACKGROUND Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key cellular signaling pathways required for growth. In contrast, progesterone via PR activation appears to increase leiomyoma growth. The exact role of PRs in cervical cancer is unclear. PRs regulate implantation and therefore aberrant PR function may be implicated in recurrent pregnancy loss (RPL). PRs likely regulate key immunogenic factors involved in RPL. However, the exact role of PRs in the pathophysiology of RPL and the use of progesterone for therapeutic benefit remains uncertain. CONCLUSIONS PRs are key mediators of progesterone action in uterine tissues and are essential for normal uterine function. Aberrant PR function (due to abnormal expression and/or function) is a major cause of uterine pathophysiology. Further investigation of the underlying mechanisms of PR isoform action in the uterus is required, as this knowledge will afford the opportunity to create progestin/PR-based therapeutics to treat various uterine pathologies. PMID:25406186

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection

PubMed Central

Di Biagio, Antonio; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice. PMID:28727818

The Relationship of Adverse Childhood Events To Smoking, Overweight, Obesity and Binge Drinking Among Women In Hawaii

PubMed Central

Remigio-Baker, Rosemay A.; Hayes, Donald K.; Reyes-Salvail, Florentina

2016-01-01

OBJECTIVES To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). METHODS The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3,354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. RESULTS Overall, 54.9% reported at least 1 ACE. The prevalence of smoking (Prevalence Ratio [PR]=1.40 [1 ACE] to PR=2.55 [5+ ACEs]), overweight (PR=1.22 [1 ACE] to PR=1.31 [5+ ACEs]) and obesity (PR=1.00 [1 ACE] to PR=1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR=1.67, CI=1.26–2.22), and physical (PR=2.04, CI=1.50–2.78) and verbal (PR=1.62, CI=1.25–2.10) abuse. Obesity was also significantly related to household dysfunction (PR=1.22, CI=1.01–1.48), and physical (PR=1.36, CI=1.10–1.70), verbal (PR=1.35, CI=1.11–1.64) and sexual (PR=1.53, CI=1.25–1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR=0.26, CI=0.07, 0.93), which was significantly different from the null association among Whites (interaction p=0.02). CONCLUSION Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs. PMID:27449778

Prioritizing Risk in Preparation for a Demonstration Project: A Mixed Methods Feasibility Study of Oral Pre-Exposure Prophylaxis (PREP) among Female Sex Workers in South India.

PubMed

Reza-Paul, Sushena; Lazarus, Lisa; Doshi, Monika; Hafeez Ur Rahman, Syed; Ramaiah, Manjula; Maiya, Raviprakash; Ms, Venugopal; Venukumar, K T; Sundararaman, Sundar; Becker, Marissa; Moses, Stephen; Lorway, Robert

2016-01-01

HIV prevalence among female sex workers (FSWs) in India remains well above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka. From January-April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data. Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a "double safety" in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95%) expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%), those who do not use condoms when clients offer more money (58%), who do not consistently use condoms with regular partners (57%), who drink alcohol regularly (49%), and who do not use condoms consistently with clients (48%). This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means of supporting PrEP uptake and adherence.

Experimental approaches to the interaction of the prion protein with nucleic acids and glycosaminoglycans: Modulators of the pathogenic conversion.

PubMed

Silva, Jerson L; Vieira, Tuane C R G; Gomes, Mariana P B; Rangel, Luciana P; Scapin, Sandra M N; Cordeiro, Yraima

2011-03-01

The concept that transmissible spongiform encephalopathies (TSEs) are caused only by proteins has changed the traditional paradigm that disease transmission is due solely to an agent that carries genetic information. The central hypothesis for prion diseases proposes that the conversion of a cellular prion protein (PrP(C)) into a misfolded, β-sheet-rich isoform (PrP(Sc)) accounts for the development of (TSE). There is substantial evidence that the infectious material consists chiefly of a protein, PrP(Sc), with no genomic coding material, unlike a virus particle, which has both. However, prions seem to have other partners that chaperone their activities in converting the PrP(C) into the disease-causing isoform. Nucleic acids (NAs) and glycosaminoglycans (GAGs) are the most probable accomplices of prion conversion. Here, we review the recent experimental approaches that have been employed to characterize the interaction of prion proteins with nucleic acids and glycosaminoglycans. A PrP recognizes many nucleic acids and GAGs with high affinities, and this seems to be related to a pathophysiological role for this interaction. A PrP binds nucleic acids and GAGs with structural selectivity, and some PrP:NA complexes can become proteinase K-resistant, undergoing amyloid oligomerization and conversion to a β-sheet-rich structure. These results are consistent with the hypothesis that endogenous polyanions (such as NAs and GAGs) may accelerate the rate of prion disease progression by acting as scaffolds or lattices that mediate the interaction between PrP(C) and PrP(Sc) molecules. In addition to a still-possible hypothesis that nucleic acids and GAGs, especially those from the host, may modulate the conversion, the recent structural characterization of the complexes has raised the possibility of developing new diagnostic and therapeutic strategies. Copyright © 2010 Elsevier Inc. All rights reserved.

The precarious balance between ‘supply’ and ‘demand’ for health care: The increasing global demand for rehabilitation service for individuals living with chronic obstructive pulmonary disease

PubMed Central

Landry, Michel D; Hamdan, Elham; Mazeedi, Sabriya Al; Brooks, Dina

2008-01-01

Chronic obstructive pulmonary disease (COPD) is becoming a critical health concern that affects people living in high-, middle-, and low-income countries. Pulmonary rehabilitation (PR) has been demonstrated to be a clinical and cost-effective approach to minimizing the effects of COPD. Despite global predictions of an increased incidence of COPD, there continues to be an important misalignment between the demand and the supply of PR services. In other words, only a small proportion of individuals with COPD who require, or would benefit from, PR programs are receiving them on the global stage. This issue may be even more pronounced in middle- and low-income countries where the burden of disease is reported to be highest, and where access to health services and trained health professionals appears be to lowest. Given this predicament, we suggest that PR services must be viewed as an effective way in which to generate clinical efficiencies within health systems, and has the potential to relieve pressure on acute care systems. Although implementing PR programs require commitment and financial investment, we argue that such investments would yield important social and aggregated financial cost savings in the long term. PMID:18990966

Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis

PubMed Central

Fishbein, Ilia; Guerrero, David T.; Alferiev, Ivan S.; Foster, Jonathan B.; Minutolo, Nicholas G.; Chorny, Michael; Mas Monteys, Alejandro; Driesbaugh, Kathryn H.; Nagaswami, Chandrasekaran; Levy, Robert J.

2017-01-01

In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty. PMID:28832561

Awareness of pre-exposure prophylaxis (PrEP) among women who inject drugs in NYC: the importance of networks and syringe exchange programs for HIV prevention.

PubMed

Walters, Suzan M; Reilly, Kathleen H; Neaigus, Alan; Braunstein, Sarah

2017-06-29

Women who inject drugs (WWID) are at heightened risk for HIV due to biological, behavioral, and structural factors. Pre-exposure prophylaxis (PrEP) could aid in HIV prevention for WWID. However, little is known about WWID awareness of PrEP, which is a necessary step that must occur before PrEP uptake. We report factors associated with greater awareness among WWID to identify efficient means of awareness dissemination. Data from the 2015 National HIV Behavioral Surveillance (NHBS) system cycle on injection drug use collected in New York City (NYC) were used. Bivariable analyses, using chi-squared statistics, were conducted to examine correlates of awareness of PrEP with socio-demographic, behavioral, and health care variables. Multivariable logistic regression was used to estimate adjusted associations and determine differences in awareness of PrEP. The analysis consisted of 118 WWID. Awareness of PrEP was relatively low (31%), and risk factors were high. In the last 12 months, almost two thirds (65%) reported condomless sex, approximately one third (31%) reported transactional sex, and one third (32%) reported sharing injection equipment. In multivariable logistic regression, increased PrEP awareness was associated with reported transactional sex (AOR 3.32, 95% CI 1.22-9.00) and having a conversation about HIV prevention at a syringe exchange program (SEP) (AOR 7.61, 95% CI 2.65-21.84). We did not find race, education, household income, age, binge drinking, or sexual identity to be significantly associated with PrEP awareness. Large proportions of WWID were unaware of PrEP. These findings suggest that social networks (specifically sex work and SEP networks) are an efficient means for disseminating messaging about prevention materials such as PrEP. We recommend that SEP access increase, SEP processes be adopted in other health care settings, and WWID networks be utilized to increase PrEP awareness.

Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma.

PubMed

Pareja, Fresia; Murray, Melissa P; Jean, Ryan Des; Konno, Fumiko; Friedlander, Maria; Lin, Oscar; Edelweiss, Marcia

2017-01-01

Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER.

Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation.

PubMed

Lou, Zhichao; Wang, Bin; Guo, Cunlan; Wang, Kun; Zhang, Haiqian; Xu, Bingqian

2015-11-01

By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Expanding the host range of small insect RNA viruses: Providence virus (Carmotetraviridae) infects and replicates in a human tissue culture cell line.

PubMed

Jiwaji, Meesbah; Short, James Roswell; Dorrington, Rosemary Ann

2016-10-01

Tetraviruses are small, positive (+ve)-sense ssRNA viruses that infect the midgut cells of lepidopteran larvae. Providence virus (PrV) is the only member of the family Carmotetraviridae (previously Tetraviridae). PrV particles exhibit the characteristic tetraviral T=4 icosahedral symmetry, but PrV is distinct from other tetraviruses with respect to genome organization and viral non-structural proteins. Currently, PrV is the only tetravirus known to infect and replicate in lepidopteran cell culture lines. In this report we demonstrate, using immunofluorescence microscopy, that PrV infects and replicates in a human tissue culture cell line (HeLa), producing infectious virus particles. We also provide evidence for PrV replication in vitro in insect, mammalian and plant cell-free systems. This study challenges the long-held view that tetraviruses have a narrow host range confined to one or a few lepidopteran species and highlights the need to consider the potential for apparently non-infectious viruses to be transferred to new hosts in the laboratory.

Tl sub 1-x Pr sub x Sr sub 2-y Pr sub y CuO sub 5-. delta. : First member of the family TlA sub 2 Ca sub m-1 Cu sub m O sub 2m+3 (A = Ba, Sr)

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

Bourgault, D.; Martin, C.; Michel, C.

1989-02-01

The synthesis, structure, and superconducting properties of the first member obtained during the investigation of the Tl-Sr-Cu-O and Tl-Sr-Pr-Cu-O systems are described. In order to check out the structural model corresponding to the first member of the series, TlSr{sub 2}Ca{sub m-1}Cu{sub m}O{sub 2m+3}, structure calculations were performed from x-ray powder data of the oxide Tl{sub 0.8}Sr{sub 1.6}Pr{sub 0.6}CuO{sub 5}. Magnetic measurements show only traces of diamagnetism for Tl{sub 0.7}Pr{sub 0.3}Sr{sub 2}CuO{sub 5-{delta}} and TlSr{sub 2}CuO{sub 5-{delta}}; however, Tl{sub 0.8}Pr{sub 0.6}Sr{sub 1.6}Cu{sub 5-{delta}} exhibits diamagnetism below 40K. 21 refs., 2 figs.

Stabilization of Phase IV in CexLa1-xB6 (x=0.4, 0.5) by Pr and Nd Ion Dopings

NASA Astrophysics Data System (ADS)

Kondo, Akihiro; Taniguchi, Toshihiro; Tanida, Hiroshi; Matsumura, Takeshi; Sera, Masafumi; Iga, Fumitoshi; Tou, Hideki; Sakakibara, Toshiro; Kunii, Satoru

2009-09-01

We have studied the effect of magnetic rare-earth ion (Pr, Nd) doping on phase IV in CexLa1-xB6 (x=0.4, 0.5) systems. An unexpected large increase in the IV-I transition temperature TIV--I by Pr and Nd dopings was observed, while no such increase was observed for x≥ 0.6. Although we do not know the reason why the doping effect markedly differs between x≤ 0.5 and x≥ 0.6 at present, the order parameter in phase IV for x≤ 0.5 is coupled with the magnetic dipole moment of Pr and Nd ions and phase IV is stabilized.

Waterborne outbreak of gastroenteritis: effects on sick leaves and cost of lost workdays.

PubMed

Halonen, Jaana I; Kivimäki, Mika; Oksanen, Tuula; Virtanen, Pekka; Virtanen, Mikko J; Pentti, Jaana; Vahtera, Jussi

2012-01-01

In 2007, part of a drinking water distribution system was accidentally contaminated with waste water effluent causing a gastroenteritis outbreak in a Finnish town. We examined the acute and cumulative effects of this incidence on sick leaves among public sector employees residing in the clean and contaminated areas, and the additional costs of lost workdays due to the incidence. Daily information on sick leaves of 1789 Finnish Public Sector Study participants was obtained from employers' registers. Global Positioning System-coordinates were used for linking participants to the clean and contaminated areas. Prevalence ratios (PR) for weekly sickness absences were calculated using binomial regression analysis. Calculations for the costs were based on prior studies. Among those living in the contaminated areas, the prevalence of participants on sick leave was 3.54 (95% confidence interval (CI) 2.97-4.22) times higher on the week following the incidence compared to the reference period. Those living and working in the clean area were basically not affected, the corresponding PR for sick leaves was 1.12, 95% CI 0.73-1.73. No cumulative effects on sick leaves were observed among the exposed. The estimated additional costs of lost workdays due to the incidence were 1.8-2.1 million euros. The prevalence of sickness absences among public sector employees residing in affected areas increased shortly after drinking water distribution system was contaminated, but no long-term effects were observed. The estimated costs of lost workdays were remarkable, thus, the cost-benefits of better monitoring systems for the water distribution systems should be evaluated.

Uncovering the Benefits of Participatory Research: Implications of a Realist Review for Health Research and Practice

PubMed Central

Jagosh, Justin; Macaulay, Ann C; Pluye, Pierre; Salsberg, Jon; Bush, Paula L; Henderson, Jim; Sirett, Erin; Wong, Geoff; Cargo, Margaret; Herbert, Carol P; Seifer, Sarena D; Green, Lawrence W; Greenhalgh, Trisha

2012-01-01

Context Participatory research (PR) is the co-construction of research through partnerships between researchers and people affected by and/or responsible for action on the issues under study. Evaluating the benefits of PR is challenging for a number of reasons: the research topics, methods, and study designs are heterogeneous; the extent of collaborative involvement may vary over the duration of a project and from one project to the next; and partnership activities may generate a complex array of both short- and long-term outcomes. Methods Our review team consisted of a collaboration among researchers and decision makers in public health, research funding, ethics review, and community-engaged scholarship. We identified, selected, and appraised a large-variety sample of primary studies describing PR partnerships, and in each stage, two team members independently reviewed and coded the literature. We used key realist review concepts (middle-range theory, demi-regularity, and context-mechanism-outcome configurations [CMO]) to analyze and synthesize the data, using the PR partnership as the main unit of analysis. Findings From 7,167 abstracts and 591 full-text papers, we distilled for synthesis a final sample of twenty-three PR partnerships described in 276 publications. The link between process and outcome in these partnerships was best explained using the middle-range theory of partnership synergy, which demonstrates how PR can (1) ensure culturally and logistically appropriate research, (2) enhance recruitment capacity, (3) generate professional capacity and competence in stakeholder groups, (4) result in productive conflicts followed by useful negotiation, (5) increase the quality of outputs and outcomes over time, (6) increase the sustainability of project goals beyond funded time frames and during gaps in external funding, and (7) create system changes and new unanticipated projects and activities. Negative examples illustrated why these outcomes were not a guaranteed product of PR partnerships but were contingent on key aspects of context. Conclusions We used a realist approach to embrace the heterogeneity and complexity of the PR literature. This theory-driven synthesis identified mechanisms by which PR may add value to the research process. Using the middle-range theory of partnership synergy, our review confirmed findings from previous PR reviews, documented and explained some negative outcomes, and generated new insights into the benefits of PR regarding conflicts and negotiation between stakeholders, program sustainability and advancement, unanticipated project activity, and the generation of systemic change. PMID:22709390

Uncovering the benefits of participatory research: implications of a realist review for health research and practice.

PubMed

Jagosh, Justin; Macaulay, Ann C; Pluye, Pierre; Salsberg, Jon; Bush, Paula L; Henderson, Jim; Sirett, Erin; Wong, Geoff; Cargo, Margaret; Herbert, Carol P; Seifer, Sarena D; Green, Lawrence W; Greenhalgh, Trisha

2012-06-01

Participatory research (PR) is the co-construction of research through partnerships between researchers and people affected by and/or responsible for action on the issues under study. Evaluating the benefits of PR is challenging for a number of reasons: the research topics, methods, and study designs are heterogeneous; the extent of collaborative involvement may vary over the duration of a project and from one project to the next; and partnership activities may generate a complex array of both short- and long-term outcomes. Our review team consisted of a collaboration among researchers and decision makers in public health, research funding, ethics review, and community-engaged scholarship. We identified, selected, and appraised a large-variety sample of primary studies describing PR partnerships, and in each stage, two team members independently reviewed and coded the literature. We used key realist review concepts (middle-range theory, demi-regularity, and context-mechanism-outcome configurations [CMO]) to analyze and synthesize the data, using the PR partnership as the main unit of analysis. From 7,167 abstracts and 591 full-text papers, we distilled for synthesis a final sample of twenty-three PR partnerships described in 276 publications. The link between process and outcome in these partnerships was best explained using the middle-range theory of partnership synergy, which demonstrates how PR can (1) ensure culturally and logistically appropriate research, (2) enhance recruitment capacity, (3) generate professional capacity and competence in stakeholder groups, (4) result in productive conflicts followed by useful negotiation, (5) increase the quality of outputs and outcomes over time, (6) increase the sustainability of project goals beyond funded time frames and during gaps in external funding, and (7) create system changes and new unanticipated projects and activities. Negative examples illustrated why these outcomes were not a guaranteed product of PR partnerships but were contingent on key aspects of context. We used a realist approach to embrace the heterogeneity and complexity of the PR literature. This theory-driven synthesis identified mechanisms by which PR may add value to the research process. Using the middle-range theory of partnership synergy, our review confirmed findings from previous PR reviews, documented and explained some negative outcomes, and generated new insights into the benefits of PR regarding conflicts and negotiation between stakeholders, program sustainability and advancement, unanticipated project activity, and the generation of systemic change. © 2012 Milbank Memorial Fund.

High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project.

PubMed

Hoagland, Brenda; Moreira, Ronaldo I; De Boni, Raquel B; Kallas, Esper G; Madruga, José Valdez; Vasconcelos, Ricardo; Goulart, Silvia; Torres, Thiago S; Marins, Luana M S; Anderson, Peter L; Luz, Paula M; Costa Leite, Iuri da; Liu, Albert Y; Veloso, Valdilea G; Grinsztejn, Beatriz

2017-04-06

The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350-699 fmol/punch and ≥700 fmol/punch). 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08-2.94). The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to address disparities on PrEP awareness and HIV risk perception among the younger and less educated are urgently needed in order to maximize the impact of this prevention strategy on the reduction of HIV infection among MSM and TGW in Brazil.

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.

PubMed

Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M; Denkers, Nathaniel D; Mathiason, Candace K; Soto, Claudio; Zabel, Mark D; Hoover, Edward A

2017-05-15

Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrP CWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state. Copyright © 2017 American Society for Microbiology.

Peer tutoring in reading: the effects of role and organization on two dimensions of self-esteem.

PubMed

Miller, David; Topping, Keith; Thurston, Allen

2010-09-01

Paired reading (PR) is an application of peer tutoring. It has been extensively researched, and its efficacy across a range of outcomes has been established. Benefits include improvements in key reading skills, and also in affective aspects of learning. Several studies have shown gains in self-esteem, although measurement methods have varied, and the model of self-esteem has rarely been clearly articulated. To investigate the changes in self-esteem of children participating in a randomized trial of PR over a 15-week treatment period. To investigate the relative contribution of self-worth and self-competence to any gains in self-esteem. To investigate whether the pattern of change differs in children who take on different roles in the PR process. The participants comprised a subset of a large-scale randomized trial of peer learning (The Fife Peer Learning Project). Four schools were randomly selected from schools allocated to the same-age PR condition, and four schools from those allocated to the cross-age PR condition. The same-age group consisted of 87 primary 6 children (10-11 years old). The cross-age group consisted of 81 primary 6 children. The controls, from schools randomly selected from a neighbouring authority, consisted of 92 primary 6 children. A pre-post design employing self-report measures of self-esteem. Rosenberg's Self-Esteem Scale was used, with scores analysed for worth and competence. The treatment period was 15 weeks, with the participants following a prescribed PR process. Significant pre-post gains were noted in self-esteem, driven predominantly by improved beliefs about competence, in both same-age and cross-age conditions, but not for controls. Gains were also seen in self-worth in the cross-age condition. Further analyses of the influence of organizational condition (same-age or cross-age) and role played (tutor vs. tutee) showed significant differences between same-age tutors and cross-age tutors in relation to self-worth. Effect sizes were generally small or moderate. The findings provide further support for the belief that PR can enhance self-esteem. Importantly, the use of a two-dimensional model provides extra information about self-perceptions in PR contexts: first, the central role of self-competence; and second, the gains in self-worth which are associated with tutoring younger children (but not same-age peers). This new information has educational significance for schools considering the potential of peer tutoring and the benefits of different organizational conditions.

Disease-Associated Prion Protein in Neural and Lymphoid Tissues of Mink (Mustela vison) Inoculated with Transmissible Mink Encephalopathy

PubMed Central

Schneider, D. A.; Harrington, R. D.; Zhuang, D.; Yan, H.; Truscott, T. C.; Dassanayake, R. P.; O'Rourke, K. I.

2012-01-01

Summary Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrPd). The distribution of PrPd within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrPTME and of which only the HY strain is associated with accumulation of PrPTME in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrPTME in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrPTME was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrPTME was detected readily in the brain and retropharyngeal lymph node during preclinical infection with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrPTME in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrPTME accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrPTME in the lymphoid tissues of mink but not in hamsters. Thus mink are a relevant animal model for further study of this unique strain, which ultimately may have been introduced through consumption of a TSE of ruminant origin. PMID:22595634

Rethinking HIV prevention to prepare for oral PrEP implementation for young African women

PubMed Central

Celum, Connie L; Delany-Moretlwe, Sinead; McConnell, Margaret; van Rooyen, Heidi; Bekker, Linda-Gail; Kurth, Ann; Bukusi, Elizabeth; Desmond, Chris; Morton, Jennifer; Baeten, Jared M

2015-01-01

Introduction HIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP). Discussion Women in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services. We reviewed behavioural, behavioural economic and biomedical approaches to HIV prevention for young African women, with a particular focus on the barriers, opportunities and implications for implementing PrEP in this group. Behavioural interventions have had limited impact in part due to not effectively addressing the context, broader sexual norms and expectations, and structural factors that increase risk and vulnerability. Of biomedical HIV prevention strategies that have been tested, daily oral PrEP has the greatest evidence for protection, although adherence was low in two placebo-controlled trials in young African women. Given high efficacy and effectiveness in other populations, demonstration projects of open-label PrEP in young African women are needed to determine the most effective delivery models and whether women at substantial risk are motivated and able to use oral PrEP with sufficient adherence to achieve HIV prevention benefits. Conclusions Social marketing, adherence support and behavioural economic interventions should be evaluated as part of PrEP demonstration projects among young African women in terms of their effectiveness in increasing demand and optimizing uptake and effective use of PrEP. Lessons learned through evaluations of implementation strategies for delivering oral PrEP, a first-generation biomedical HIV prevention product, will inform development of new and less user-dependent PrEP formulations and delivery of an expanding choice of prevention options in HIV prevention programmes for young African women. PMID:26198350

Identification of allocryptopine and protopine metabolites in rat liver S9 by high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.

PubMed

Huang, Ya-Jun; Xiao, Sa; Sun, Zhi-Liang; Zeng, Jian-Guo; Liu, Yi-Song; Liu, Zhao-Ying

2016-07-15

Allocryptopine (AL) and protopine (PR) have been extensively studied because of their anti-parasitic, anti-arrhythmic, anti-thrombotic, anti-inflammatory and anti-bacterial activity. However, limited information on the pharmacokinetics and metabolism of AL and PR has been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of AL and PR in rat liver S9 using a rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOFMS) method. The incubation mixture was processed with 15% trichloroacetic acid (TCA). Multiple scans of AL and PR metabolites and accurate mass measurements were automatically performed simultaneously through data-dependent acquisition in only a 30-min analysis. The structural elucidations of these metabolites were performed by comparing their changes in accurate molecular masses and product ions with those of the precursor ion or metabolite. Eight and five metabolites of AL and PR were identified in rat liver S9, respectively. Among these metabolites, seven and two metabolites of AL and PR were identified in the first time, respectively. The demethylenation of the 2,3-methylenedioxy, the demethylation of the 9,10-vicinal methoxyl group and the 2,3-methylenedioxy group were the main metabolic pathways of AL and PR in liver S9, respectively. In addition, the cleavage of the methylenedioxy group of the drugs and subsequent methylation or O-demethylation were also the common metabolic pathways of drugs in liver S9. In addition, the hydroxylation reaction was also the metabolic pathway of AL. This was the first investigation of in vitro metabolism of AL and PR in rat liver S9. The detailed structural elucidations of AL and PR metabolites were performed using a rapid and accurate HPLC/QqTOFMS method. The metabolic pathways of AL and PR in rat were tentatively proposed based on these characterized metabolites and early reports. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study

PubMed Central

Colby, Donn; Srithanaviboonchai, Kriengkrai; Vanichseni, Suphak; Ongwandee, Sumet; Phanuphak, Nittaya; Martin, Michael; Choopanya, Kachit; Chariyalertsak, Suwat; van Griensven, Frits

2015-01-01

Introduction Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization as an effective method of HIV prevention for individuals at risk for infection. In this paper, we describe the unique role that Thailand has played in the global effort to combat the HIV epidemic, including its role in proving the efficacy of PrEP, and discuss the opportunities and challenges of implementing PrEP in a middle-income country. Discussion Thailand was one of the first countries in the world to successfully reverse a generalized HIV epidemic. Despite this early success, HIV prevalence has remained high among people who inject drugs and has surged among men who have sex with men (MSM) and transgender women (TGW). Two pivotal trials that showed that the use of oral antiretroviral medication as PrEP can reduce HIV transmission were conducted partially or entirely at Thai sites. Demonstration projects of PrEP, as well as clinical trials of alternative PrEP regimens, began or will begin in 2014–2015 in Thailand and will provide additional data and experience on how to best implement PrEP for high-risk individuals in the community. Financing of drug costs, the need for routine laboratory monitoring and lack of awareness about PrEP among at-risk groups all present challenges to the wider implementation of PrEP for HIV prevention in Thailand. Conclusions Although significant challenges to wider use remain, PrEP holds promise as a safe and highly effective method to be used as part of a combined HIV prevention strategy for MSM and TGW in Thailand. PMID:26198342

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

PubMed Central

Wheeler, Stephanie B.; Stranix-Chibanda, Lynda; Hosek, Sybil G.; Watts, D. Heather; Siberry, George K.; Spiegel, Hans M. L.; Stringer, Jeffrey S.; Chi, Benjamin H.

2016-01-01

Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. Methods: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. Results: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. Conclusions: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy. PMID:27355502

A visual dual-aptamer logic gate for sensitive discrimination of prion diseases-associated isoform with reusable magnetic microparticles and fluorescence quantum dots.

PubMed

Xiao, Sai Jin; Hu, Ping Ping; Chen, Li Qiang; Zhen, Shu Jun; Peng, Li; Li, Yuan Fang; Huang, Cheng Zhi

2013-01-01

Molecular logic gates, which have attracted increasing research interest and are crucial for the development of molecular-scale computers, simplify the results of measurements and detections, leaving the diagnosis of disease either "yes" or "no". Prion diseases are a group of fatal neurodegenerative disorders that happen in human and animals. The main problem with a diagnosis of prion diseases is how to sensitively and selectively discriminate and detection of the minute amount of PrP(Res) in biological samples. Our previous work had demonstrated that dual-aptamer strategy could achieve highly sensitive and selective discrimination and detection of prion protein (cellular prion protein, PrP(C), and the diseases associated isoform, PrP(Res)) in serum and brain. Inspired by the advantages of molecular logic gate, we further conceived a new concept for dual-aptamer logic gate that responds to two chemical input signals (PrP(C) or PrP(Res) and Gdn-HCl) and generates a change in fluorescence intensity as the output signal. It was found that PrP(Res) performs the "OR" logic operation while PrP(C) performs "XOR" logic operation when they get through the gate consisted of aptamer modified reusable magnetic microparticles (MMPs-Apt1) and quantum dots (QDs-Apt2). The dual-aptamer logic gate simplifies the discrimination results of PrP(Res), leaving the detection of PrP(Res) either "yes" or "no". The development of OR logic gate based on dual-aptamer strategy and two chemical input signals (PrP(Res) and Gdn-HCl) is an important step toward the design of prion diseases diagnosis and therapy systems.

Palladium(II) complexes with highly basic imidazolin-2-imines and their reactivity toward small bio-molecules.

PubMed

Bogojeski, Jovana; Volbeda, Jeroen; Freytag, Matthias; Tamm, Matthias; Bugarčić, Živadin D

2015-10-21

A series of novel Pd(ii) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands were synthesized. The crystal structures of [Pd(DMEAIm(iPr))Cl2] and [Pd(DPENIm(iPr))Cl2] were determined by X-ray diffraction analysis. The reactivity of the six Pd(ii) complexes, namely, [Pd(en)Cl2], [Pd(EAIm(iPr))Cl2], [Pd(DMEAIm(iPr))Cl2], [Pd(DPENIm(iPr))Cl2], [Pd(BL(iPr))Cl2] and [Pd(DACH(Im(iPr))2)Cl2], were investigated. Spectrophotometric acid-base titrations were performed to determine the pKa values of the coordinated water molecules in [Pd(en)(H2O)2](2+), [Pd(EAIm(iPr))(H2O)2](2+), [Pd(DMEAIm(iPr))(H2O)2](2+), [Pd(DPENIm(iPr))(H2O)2](2+), [Pd(BL(iPr))(H2O)2](2+) and [Pd(DACH(Im(iPr))2)(H2O)2](2+). The substitution of the chloride ligands in these complexes by TU, l-Met, l-His and Gly was studied under pseudo-first-order conditions as a function of the nucleophile concentration and temperature using stopped-flow techniques; the sulfur-donor nucleophiles have shown better reactivity than nitrogen-donor nucleophiles. The obtained results indicate that there is a clear correlation between the nature of the imidazolin-2-imine ligands and the acid-base characteristics and reactivity of the resulting Pd(ii) complexes; the order of reactivity of the investigated Pd(ii) complexes is: [Pd(en)Cl2] > [Pd(EAIm(iPr))Cl2] > [Pd(DMEAIm(iPr))Cl2] > [Pd(DPENIm(iPr))Cl2] > [Pd(BL(iPr))Cl2] > [Pd(DACH(Im(iPr))2)Cl2]. The solubility measurements revealed good solubility of the studied imidazolin-2-imine complexes in water, despite the fact that these Pd(ii) complexes are neutral complexes. Based on the performed studies, three unusual features of the novel imidazolin-2-imine Pd(ii) complexes are observed, that is, good solubility in water, very low reactivity and high pKa values. The coordination geometries around the palladium atoms are distorted square-planar; the [Pd(DMEAIm(iPr))Cl2] complex displays Pd-N distances of 2.013(2) and 2.076(2) Å, while the [Pd(DPENIm(iPr))Cl2] complex displays similar Pd-N distances of 2.034(4) and 2.038(3) Å. The studied systems are of interest because little is known about the substitution behavior of imidazolin-2-imine Pd(ii) complexes with bio-molecules under physiological conditions.

Exoplanets: The Hunt Continues!

NASA Astrophysics Data System (ADS)

2001-04-01

Swiss Telescope at La Silla Very Successful Summary The intensive and exciting hunt for planets around other stars ( "exoplanets" ) is continuing with great success in both hemispheres. Today, an international team of astronomers from the Geneva Observatory and other research institutes [1] is announcing the discovery of no less than eleven new, planetary companions to solar-type stars, HD 8574, HD 28185, HD 50554, HD 74156, HD 80606, HD 82943, HD 106252, HD 141937, HD 178911B, HD 141937, among which two new multi-planet systems . The masses of these new objects range from slightly less than to about 10 times the mass of the planet Jupiter [2]. The new detections are based on measured velocity changes of the stars [3], performed with the CORALIE spectrometer on the Swiss 1.2-m Leonard Euler telescope at the ESO La Silla Observatory , as well as with instruments on telescopes at the Haute-Provence Observatory and on the Keck telescopes on Mauna Kea (Hawaii, USA). Some of the new planets are unusual: * a two-planet system (around the star HD 82943) in which one orbital period is nearly exactly twice as long as the other - cases like this (refered to as "orbital resonance") are well known in our own solar system; * another two-planet system (HD 74156), with a Jupiter-like planet and a more massive planet further out; * a planet with the most elongated orbit detected so far (HD 80606), moving between 5 and 127 million kilometers from the central star; * a giant planet moving in an orbit around its Sun-like central star that is very similar to the one of the Earth and whose potential satellites (in theory, at least) might be "habitable". At this moment, there are 63 know exoplanet candidates with minimum masses below 10 Jupiter masses, and 67 known objects with minimum masses below 17 Jupiter masses. The present team of astronomers has detected about half of these. PR Photo 13a/01 : Radial-velocity measurements of HD 82943, a two-planet system . PR Photo 13b/01 : Radial-velocity measurements of HD 80606, a star with a planet in a very elongated orbit . A major international effort The discovery of eleven new exoplanets has resulted from three high-precision radial-velocity surveys now searching for such objects: * The CORALIE planet-search programme on La Silla [4], conducted by astronomers of the Geneva Observatory [1] * The ELODIE high-precision radial-velocity survey of solar-type stars at the Haute-Provence Observatory (OHP/France) conducted by a Swiss-French team, including the Geneva, Grenoble and Haute-Provence Observatories [1] * The G-dwarf project , an ELODIE-HIRES/Keck planet-search programme set up by a team of astronomers from the Geneva Observatory, the Center for Astrophysics (Cambridge, Mass., USA) and the Tel Aviv University (Israel) [1] The new results are the outcome of high-precision radial-velocity measurements . This fundamental observational method is based on the detection of changes in the velocity of the central star , due to the changing direction of the gravitational pull from an (unseen) exoplanet as it orbits the star. The evaluation of the measured velocity variations allows to deduce the planet's orbit , in particular the period and the distance from the star, as well as a minimum mass [3]. Four of the new planets were detected from La Silla and three ELODIE candidates were secured with CORALIE measurements. With the eleven new discoveries, the CORALIE/ELODIE programmes have contributed to the detection of about half (32) of the known (63) planetary candidates with minimum masses below 10 Jupiter masses, or 36 out of 67 known objects with minimum masses below 17 Jupiter masses [2]. Several unusual systems Among the present detections, there are two new planetary systems (HD 82943 and HD 74156), each with two planets. They bring to six the number of known multi-planet systems, four of which owe their detection to CORALIE/ELODIE measurements. This demonstrates the outstanding role that comparatively small telescopes can still play in modern astrophysics. Detailed information about all of the new planets are available on the dedicated web page at the Geneva Observatory web site: http://obswww.unige.ch/~udry/planet/new_planet.html. Of the systems discovered at La Silla, two are quite unusual: HD 82943: a "resonant" system ESO PR Photo 13a/01 ESO PR Photo 13a/01 [Preview - JPEG: 367 x 400 pix - 53k] [Normal - JPEG: 734 x 800 pix - 248k] Caption : PR Photo 13a/01 shows the radial-velocity measurements of the central star, 82493 , in a two-planet system, as observed with the CORALIE instrument at La Silla. The best-fit curve corresponds to expected variations, caused by the planets described in the text. The abscissa shows the date; the ordinate the velocity The detection of the outer planet that orbits the star HD 82943 was announced earlier ( ESO Press Release 13/00 ), together with seven CORALIE planet candidates at other stars. The follow-up observations at La Silla soon revealed a departure from the previously determined orbit. The accumulated measurements ( PR Photo 13a/01 ) now allow the detection of a second, inner planet in this system. Its orbital period (221 days) is about half of that of the outer one (444 days). Future observations should confirm the 1:2 ratio between the periods; this indicates a "resonance" that may result from the gravitational interaction between the two planets. Similar orbital resonances are known in the solar system, especially in case of the minor planets (asteroids). HD 28185: a giant planet in the "habitable" zone With the exception of the planet iota Hor b (cf. ESO PR 12/99 ), circular orbits among exoplanets have only been found for short-period systems, contrary to what is the case for the giant planets in our own Solar System. However, the orbit of the newly found planet near the sun-like star HD 28185 is very nearly circular and with a period of 385 days (close to 1 Earth year), its distance from the star, 150.6 million km, is almost equal to the distance betwen the Sun and the Earth (149.6 million km). This new planet is therefore located in the "habitable zone" where temperatures like those on the Earth are possible. Still, it is a giant, gaseous planet (with a minimum mass of 3.5 times that of Jupiter, or about 1000 times that of the Earth) and thus an unlikely place for the development of life. Nevertheless, it may be orbited by one or more moons on which a more bio-friendly environment has evolved. The presence of natural satellites ("moons") around giant extra-solar planets is not a far-fetched idea, just look at our own Solar System. HD 80606: a giant planet in an extremely elongated orbit ESO PR Photo 13b/01 ESO PR Photo 13b/01 [Preview - JPEG: 400 x 233 pix - 21k] [Normal - JPEG: 800 x 465 pix - 41k] Caption : PR Photo 13b/01 shows the radial-velocity measurements of the star HD 80606 that hosts a planet in a very eccentric orbit. A planet in an extremely elongated orbit around the star HD 80606 was found in the frame of the ELODIE/Keck collaboration. The measured, very large eccentricity (e = 0.93; PR Photo 13b/01 ) implies of factor of no less than 26 between the smallest and largest distance to the star. When the planet is closest to the star, it is only a few stellar radii away (about 5 million kilometres). Continuation of the programme Further progress within the current programme is expected soon, when the Very Large Telescope Interferometer (VLTI) at Paranal becomes available, cf. ESO PR 06/01. This new instrument will have the observational capability of very high-accuracy positional measurements (astrometry) and thus be able to detect even very small wobbles of stellar positions in the sky that are due to the pull of orbiting planets. This will provide a crucial contribution to the determination of the true repartition of exoplanetary masses, a hotly debated question. Important advancement in our understanding of the formation of planetary systems is also expected with the advent of HARPS. This new high-resolution spectrograph, capable of reaching the extremely high radial-velocity precision of 1 m/sec, will be installed on the ESO 3.6-m telescope at La Silla at the end of 2002. HARPS will extend the domain of planets accessible with the radial-velocity technique towards significantly lower masses - down to about ten Earth masses on short-period orbits . It will also greatly improve our capability of detecting planets with longer periods and multi-planet systems. More information More information on these discoveries may be found in a Press Release from the Tel Aviv University and on the Geneva planet-search web page. Notes [1] The team consists of: Geneva Observatory (Switzerland): Michel Mayor, Dominique Naef, Francesco Pepe, Didier Queloz, Nuno C. Santos, Stephane Udry, Michel Burnet Grenoble Observatory (France): Christian Perrier, Jean-Luc Beuzit Haute-Provence Observatory (France): Jean-Pierre Sivan Center for Astrophysics (Cambridge, Mass., USA): David Latham, Guillermo Torres Tel Aviv University (Israel): Tsevi Mazeh, Shay Zucker, G. Drukier [2] The mass units for the exoplanets used in this text are 1 Jupiter mass = 318 Earth masses. [3] A fundamental limitation of the radial-velocity method, currently used by all planet-hunting research teams, is that because of the uncertainty of the inclination of the planetary orbit, it only allows to determine a lower mass limit for the planet. However, statistical considerations indicate that in most cases, the true mass will not be much higher than this value. [4] Earlier accounts of this research programme have been published as ESO Press Release 18/98 and ESO Press Release 13/00. Views of the 1.2-m Leonard Euler telescope and its dome at La Silla are available as PR Photos 13a-c/00.

Effect of informal employment on the relationship between psychosocial work risk factors and musculoskeletal pain in Central American workers.

PubMed

Gimeno Ruiz de Porras, David; Rojas Garbanzo, Marianela; Aragón, Aurora; Carmenate-Milián, Lino; Benavides, Fernando G

2017-09-01

The constant increase on the psychosocial demands experienced at work seems to contribute to the increase in health problems such as musculoskeletal pain (MSP). This association may be especially important in low-income and middle-income countries, where there is a large proportion of informal workers among whom there is little research. We analysed the association between psychosocial work risk factors and MSP among formal and informal workers using the First Central American Survey of Working Conditions and Health. This is a representative sample (n=12 024) of the economically active population of the six Spanish-speaking countries of Central America. Prevalence ratios (PR) and corresponding 95% CIs from Poisson regression models were used to estimate the association between psychosocial work risk factors and the MSP. Compared with formal workers, informal workers reported higher prevalence of MPS in the body regions analysed (ie, cervicodorsal, lumbosacral, upper extremities) and higher exposure to psychosocial work risk factors. However, on the whole, the associations between the exposure to psychosocial work risk factors and the prevalence of MSP were similar for both formal and informal workers. Only the association between exposure to high demands and MSP in the upper extremities was higher (p=0.012) among formal (PR=1.69, 95% CI 1.46 to 1.96) than among informal workers (PR=1.40; 95% CI 1.30 to 1.51). Exposure to adverse levels of psychosocial work risk factors is associated with higher prevalence of MPS among both formal and informal workers. However, the role of employment informality in this association is complex and requires further examination. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Parental Communication, Engagement, and Support During the Adolescent Voluntary Medical Male Circumcision Experience

PubMed Central

Dam, Kim H; Kaufman, Michelle R; Patel, Eshan U; Van Lith, Lynn M; Hatzold, Karin; Marcell, Arik V; Mavhu, Webster; Kahabuka, Catherine; Mahlasela, Lusanda; Njeuhmeli, Emmanuel; Seifert Ahanda, Kim; Ncube, Getrude; Lija, Gissenge; Bonnecwe, Collen; Tobian, Aaron A R

2018-01-01

Abstract Background Voluntary medical male circumcision (VMMC) is one of few opportunities in sub-Saharan Africa to engage male adolescents in the healthcare system. Limited data are available on the level of parental communication, engagement, and support adolescents receive during the VMMC experience. Methods We conducted 24 focus group discussions with parents/guardians of adolescents (N = 192) who agreed to be circumcised or were recently circumcised in South Africa, Tanzania, and Zimbabwe. In addition, male adolescents (N = 1293) in South Africa (n = 299), Tanzania (n = 498), and Zimbabwe (n = 496) were interviewed about their VMMC experience within 7–10 days postprocedure. We estimated adjusted prevalence ratios (aPRs) using multivariable Poisson regression with generalized estimating equations and robust standard errors. Results Parents/guardians noted challenges and gaps in communicating with their sons about VMMC, especially when they did not accompany them to the clinic. Adolescents aged 10–14 years were significantly more likely than 15- to 19-year-olds to report that their parent accompanied them to a preprocedure counseling session (56.5% vs 12.5%; P < .001). Among adolescents, younger age (aPR, 0.86; 95% confidence interval [CI], .76–.99) and rural setting (aPR, 0.34; 95% CI, .13–.89) were less likely to be associated with parental–adolescent communication barriers, while lower socioeconomic status (aPR, 1.37; 95% CI, 1.00–1.87), being agnostic (or of a nondominant religion; aPR, 2.87; 95% CI, 2.21–3.72), and living in South Africa (aPR, 2.63; 95% CI, 1.29–4.73) were associated with greater perceived barriers to parental–adolescent communication about VMMC. Parents/guardians found it more difficult to be involved in wound care for older adolescents than for adolescents <15 years of age. Conclusions Parents play a vital role in the VMMC experience, especially for younger male adolescents. Strategies are needed to inform parents completely throughout the VMMC adolescent experience, whether or not they accompany their sons to clinics. PMID:29617779

Study design for a randomised controlled trial to explore the modality and mechanism of Tai Chi in the pulmonary rehabilitation of chronic obstructive pulmonary disease.

PubMed

Fu, Juan-Juan; Min, Jie; Yu, Peng-Ming; McDonald, Vanessa M; Mao, Bing

2016-08-04

Although pulmonary rehabilitation (PR) is associated with significant clinical benefits in chronic obstructive pulmonary disease (COPD) and has been recommended by guidelines, PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations. Alternative exercise such as Tai Chi has been investigated and the results are promising. However, the strengths and weaknesses of the exercise modality of Tai Chi, conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear. This study aims to address the above research gaps in a well-designed clinical trial. This study is a single-blind, randomised controlled trial. Participants with stable COPD will be recruited and randomly assigned to one of four groups receiving Tai Chi exercise, conventional PR using a total body recumbent stepper (TBRS), combined Tai Chi and TBRS, or usual care (control) in a 1:1:1:1 ratio. Participants will perform 30 min of supervised exercise three times a week for 8 weeks; they will receive sequential follow-ups until 12 months after recruitment. The primary outcome will be health-related quality of life as measured by the St George's Respiratory Questionnaire. Secondary outcomes will include 6 min walking distance, pulmonary function, the modified Medical Research Council Dyspnoea Scale, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, the Berg Balance Scale, exacerbation frequency during the study period, and systemic inflammatory and immune markers. Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No TCM-2015-82). Written informed consent will be obtained from each participant before any procedures are performed. The study findings will be published in peer-reviewed journals and presented at national and international conferences. ChiCTR-IOR-15006874; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Challenges and opportunities in establishing a collaborative multisite observational study of chronic diseases and lifestyle factors among adults in Puerto Rico.

PubMed

Mattei, Josiemer; Rodríguez-Orengo, José F; Tamez, Martha; Corujo, Francheska; Claudio, Aida; Villanueva, Héctor; Campos, Hannia; Willett, Walter C; Tucker, Katherine L; Ríos-Bedoya, Carlos F

2017-01-31

Prevalence of chronic diseases and unhealthy lifestyle behaviors among the adult population of Puerto Rico (PR) is high; however, few epidemiological studies have been conducted to address these. We aimed to document the methods and operation of establishing a multisite cross-sectional study of chronic diseases and risk factors in PR, in partnership with academic, community, clinical, and research institutions. The Puerto Rico Assessment of Diet, Lifestyle and Diseases (PRADLAD) documented lifestyle and health characteristics of adults living in PR, with the goal of informing future epidemiological and intervention projects, as well as public health, policy, and clinical efforts to help improve the population's health. The study was conducted in three primary care clinics in the San Juan, PR metropolitan area. Eligible volunteers were 30-75y, living in PR for at least 10 months of the previous year, and able to answer interviewer-administered questionnaires without assistance. Questions were recorded electronically by trained interviewers, and included socio-demographic characteristics, lifestyle behaviors, self-reported medically-diagnosed diseases, and psychosocial factors. Waist and hip circumferences were measured following standardized protocols. A subset of participants answered a validated food frequency questionnaire, a legumes questionnaire, and had medical record data abstracted. Process and outcome evaluation indicators were assessed. The study screened 403 participants in 5 months. Of these, 396 (98%) were eligible and 380 (94%) had reliable and complete information. A subset of 242 participants had valid dietary data, and 236 had medical record data. The mean time to complete an interview was 1.5 h. Participants were generally cooperative and research collaborators were fully engaged. Having multiple sites helped enhance recruitment and sociodemographic representation. Diagnosed conditions were prevalent across sites. Challenges in data monitoring, interviewer training, and scheduling were identified and corrected, and should be addressed in future studies. Epidemiological studies in PR can be successfully implemented in partnership with multiple institutions. Effective recruitment and implementation requires concerted planning and continued involvement from partners, frequent quality control, brief interviews, reasonable incentives, and thorough training/re-training of culturally-sensitive interviewers. Further studies are feasible and needed to help address highly prevalent chronic conditions in PR.

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

PubMed

Lopes, M H; Santos, T G; Rodrigues, B R; Queiroz-Hazarbassanov, N; Cunha, I W; Wasilewska-Sampaio, A P; Costa-Silva, B; Marchi, F A; Bleggi-Torres, L F; Sanematsu, P I; Suzuki, S H; Oba-Shinjo, S M; Marie, S K N; Toulmin, E; Hill, A F; Martins, V R

2015-06-01

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

Induction of salicylic acid-mediated defense response in perennial ryegrass against infection by Magnaporthe oryzae.

PubMed

Rahman, Alamgir; Kuldau, Gretchen A; Uddin, Wakar

2014-06-01

Incorporation of plant defense activators is an innovative approach to development of an integrated strategy for the management of turfgrass diseases. The effects of salicylic acid (SA), benzothiadiazole (BTH, chemical analog of SA), jasmonic acid (JA), and ethephon (ET, an ethylene-releasing compound) on development of gray leaf spot in perennial ryegrass (Lolium perenne L.) caused by Magnaporthe oryzae were evaluated. Gray leaf spot disease incidence and severity were significantly decreased when plants were treated prior to inoculation with SA, BTH, and partially by ET but not by JA. Accumulation of endogenous SA and elevated expression of pathogenesis-related (PR)-1, PR-3.1, and PR-5 genes were associated with inoculation of plants by M. oryzae. Treatment of plants with SA enhanced expression levels of PR-3.1 and PR-5 but did not affect the PR-1 level, whereas BTH treatment enhanced relative expression levels of all three PR genes. Microscopic observations of leaves inoculated with M. oryzae revealed higher frequencies of callose deposition at the penetration sites in SA- and BTH-treated plants compared with the control plants (treated with water). These results suggest that early and higher induction of these genes by systemic resistance inducers may provide perennial ryegrass with a substantial advantage to defend against infection by M. oryzae.

Time-course study of retinal pathology in C57BL/6 mice infected with RML scrapie

USDA-ARS?s Scientific Manuscript database

Prions are proteinaceous pathogens that cause transmissible spongiform encephalopathies (TSEs). These diseases develop slowly as the misfolded and protease-resistant prion protein, PrP**Sc, interacts with the normal cellular form, PrP**C, a cell-surface protein found throughout the nervous system. T...

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

USDA-ARS?s Scientific Manuscript database

Classical scrapie is a form of transmissible spongiform encephalopathies (TSE) affecting domestic goats and sheep and disease is characterized by the accumulation of abnormal conformational isoform (PrP-Sc) of normal cellular prion protein (PrP-C) in the central nervous system and, in most cases, ly...

Antiprion activity of DB772 and related monothiophene-and furan-based analogs in a persistently infected ovine microglia culture system

USDA-ARS?s Scientific Manuscript database

The transmissible spongiform encephalopathies are fatal neurodegenerative disorders characterized by the misfolding of the native cellular prion protein (PrP-C) into the accumulating, disease-associated isoform (PrP-Sc). Despite extensive research into the inhibition of prion accumulation, no effect...

Papayas and Pedagogy: Geographically Dispersed Teams and Internet Self-Efficacy.

ERIC Educational Resources Information Center

O'Malley, Michelle; Kelleher, Tom

2002-01-01

Describes how public relations (PR) students' Internet self-efficacy (e-mail, bulletin board system, real-time chat, and Web research) was measured before, immediately after, and 7 weeks after they worked in either geographically dispersed (Kansas and Hawaii) or local (Kansas only) teams to develop a PR issue statement. Finds Internet efficacy…

Systemic resistance induced in Arabidopsis thaliana by Trichoderma asperellum SKT-1, a microbial pesticide of seedborne diseases of rice.

PubMed

Yoshioka, Yohei; Ichikawa, Haruki; Naznin, Hushna Ara; Kogure, Atsushi; Hyakumachi, Mitsuro

2012-01-01

Trichoderma asperellum SKT-1 is a microbial pesticide of seedborne diseases of rice. To investigate the mechanisms of disease suppression in SKT-1, the ability to induce systemic resistance by SKT-1, or its cell-free culture filtrate (CF), was tested using Arabidopsis thaliana Col-0 plants. Both SKT-1 and its CF elicit an induced systemic resistance against the bacterial leaf speck pathogen Pseudomonas syringae pv. tomato DC3000 in Col-0 plants. Involvement of plant hormones in the induced resistance by SKT-1 and CF was assessed using Arabidopsis genotypes such as the jasmonic acid (JA)-resistant mutant jar1, the ethylene (ET)-resistant mutant etr1, the plant impaired in salicylic acid (SA) signalling transgenic NahG and the mutant npr1 impaired in NPR1 activity. In soil experiments using SKT-1, no significant disease suppression effect was observed in NahG transgenic plants or npr1 mutant plants. Expression levels of SA-inducible genes such as PR-1, PR-2 and PR-5 increased substantially in the leaves of Col-0 plants. Expression levels of JA/ET-induced genes such as PDF1.2a, PR-3, PR-4 and AtVsp1 were also induced, but the levels were not as high as for SA-inducible genes. In a hydroponic experiment using CF from SKT-1, all Arabidopsis genotypes showed an induced systemic resistance by CF and increased expression levels of JA/ET- and SA-inducible genes in leaves of CF-treated plants. The SA signalling pathway is important in inducing systemic resistance to colonisation by SKT-1, and both SA and JA/ET signalling pathways combine in the signalling of induced resistance by CF. These results indicate that the response of A. thaliana is different from that found in root treatments with barley grain inoculum and CF from SKT-1. Copyright © 2011 Society of Chemical Industry.

Solvent influence on complex formation between Cd2+ and 2-hydroxy-1,4-naphthoquinone in binary mixed nonaqueous solvents at 15-45°C

NASA Astrophysics Data System (ADS)

Farazandeh, R.; Rounaghi, G. H.; Ebrahimi, M.; Basafa, S.

2017-04-01

The complexation reaction of Cd2+ cation with 2-hydroxy-1,4-naphthoquinone (HNQ) was studied in acetonitrile (AN), 2-PrOH, ethyl acetate (EtOAc), EtOH, dimethylformamide (DMF) and in binary solutions AN-2-PrOH, AN-DMF, AN-EtOH, and AN-EtOAc using conductometric method at 15-45°C. The conductance data show that the stoichiometry of the Cd2+ complex with HNQ in all solvent systems is 1 : 1. In the pure solvents the stability of the complex changes in the order AN > 2-PrOH > EtOH > DMF. The stability of the complex at 25°C in the studied mixtures changes in the following order : AN-EtOAc > AN-2-PrOH > AN-EtOH > AN-DMF. These orders are affected by the nature and composition of the solvent systems and by the temperature. From the temperature dependence data, the thermodynamic functions values (Δ H° and Δ S°) for the complex formation were calculated.

Biosorption of praseodymium (III) using Terminalia arjuna bark powder in batch systems: isotherm and kinetic studies.

PubMed

Swain, Krishna Kumari; Mishra, Pravat Manjari; Devi, Aparna Prabha

2018-02-01

The high demand for rare earth elements (REEs) used in various advanced materials implies demand for increased production of REEs or the recycling of solutions to recover the REEs they contain. In this study, the biosorption of Pr(III) from aqueous solution by bark powder of Terminalia arjuna was examined in a batch system as a function of metal concentration, biosorbent dosage, pH and contact time. Results showed that T. arjuna bark powder has a high affinity for adsorbing Pr(III): more than 90% at pH 6.63. The adsorption of Pr(III) by T. arjuna bark powder was investigated by the Langmuir, Freundlich, Temkin and Dubinin-Radushkevich isotherm models. The kinetics of the biosorption process was tested with pseudo-first-order and pseudo-second-order models, and the results showed that the biosorption process was better fitted to the pseudo-second-order model. From Fourier transform infrared spectroscopy (FT-IR) analysis, it is confirmed that the biomolecules of T. arjuna bark powder are involved in the biosorption process of Pr(III) metal ions.

Production of single-round infectious chimeric flaviviruses with DNA-based Japanese encephalitis virus replicon.

PubMed

Suzuki, Ryosuke; Ishikawa, Tomohiro; Konishi, Eiji; Matsuda, Mami; Watashi, Koichi; Aizaki, Hideki; Takasaki, Tomohiko; Wakita, Takaji

2014-01-01

A method for rapid production of single-round infectious particles (SRIPs) of flavivirus would be useful for viral mutagenesis studies. Here, we established a DNA-based production system for SRIPs of flavivirus. We constructed a Japanese encephalitis virus (JEV) subgenomic replicon plasmid, which lacked the C-prM-E (capsid-pre-membrane-envelope) coding region, under the control of the cytomegalovirus promoter. When the JEV replicon plasmid was transiently co-transfected with a JEV C-prM-E expression plasmid into 293T cells, SRIPs were produced, indicating successful trans-complementation with JEV structural proteins. Equivalent production levels were observed when C and prM-E proteins were provided separately. Furthermore, dengue types 1-4, West Nile, yellow fever or tick-borne encephalitis virus prM-E proteins could be utilized for production of chimaeric flavivirus SRIPs, although the production was less efficient for dengue and yellow fever viruses. These results indicated that our plasmid-based system is suitable for investigating the life cycles of flaviviruses, diagnostic applications and development of safer vaccine candidates.

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

PubMed

Haberer, Jessica E; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A; Ware, Norma C; Thomas, Katherine K; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie; Bangsberg, David R

2013-01-01

Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

Composition anisotropy compensation and magnetostriction of Co-doped Laves compounds Tb0.2Dy0.8-xPrxFe1.93 (0 ≤ x ≤ 0.40)

NASA Astrophysics Data System (ADS)

Li, F.; Liu, J. J.; Zhu, X. Y.; Shen, W. C.; Lin, L. L.; Du, J.; Si, P. Z.

2018-07-01

Alloys of Tb0.2Dy0.8-xPrx(Fe0.8Co0.2)1.93 (0 ≤ x ≤ 0.40) are arc melted and investigated for structural, magnetic and magnetoelastic properties by means of X-ray diffraction (XRD), a vibrating sample magnetometer and a standard strain technique. The 20 at.% Co substitution for Fe is shown to enable the formation of the single Laves phase with a high Pr content up to x = 0.25. Experimental evidence for magnetocrystalline-anisotropy compensation between Pr3+ and Dy3+ ions is obtained in the Laves phase system. The easy magnetization direction (EMD) at room temperature rotates from <100> to <110> axis when x increases from 0 to 0.40. The linear anisotropic magnetostriction λa (=λ||-λ⊥) increases with increasing Pr content when x ≤ 0.25 ascribed to both the larger magnetostriction of PrFe2 than that of DyFe2 and the decrease of the resulted anisotropy due to compensation. The composition anisotropy compensation is found to be around x = 0.25, shifting to the Pr-rich side at room temperature as compared to the Co-free counterpart Tb0.2Dy0.8-xPrxFe1.93 system. The Tb0.2Dy0.55Pr0.25(Fe0.8Co0.2)1.93 alloy has good magnetoelastic properties at room temperature, that is, a low anisotropy and a high low-field magnetostriction λa ∼140 ppm at 1 kOe.

The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner.

PubMed

Rea, Kieran; McGowan, Fiona; Corcoran, Louise; Roche, Michelle; Finn, David P

2018-05-30

The emotional processing and coordination of top-down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC, (infralimbic (IL), prelimbic (PrL), anterior cingulate (ACC) cortices), differentially alter the expression of contextually-induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IL, PrL and ACC in formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-mPFC administration of AM251 (CB 1 receptor antagonist/inverse agonist), URB597 (fatty acid amide hydrolase inhibitor) or URB597 + AM251 on FCA and freezing behaviour were assessed. AM251 attenuated FCA when injected into the IL or PrL and reduced contextually induced freezing behaviour when injected intra-IL, but not intra-PrL or intra-ACC. Intra-ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra-IL, prolonged the expression of FCA when injected intra-PrL and had no effect on these behaviours when injected intra-ACC. These results suggest important and differential roles for FAAH substrates or CB 1 receptors in the PrL, IL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone. This article is protected by copyright. All rights reserved.

Erosion risk analysis by GIS in environmental impact assessments: a case study--Seyhan Köprü Dam construction.

PubMed

Sahin, S; Kurum, E

2002-11-01

Environmental Impact Assessment (EIA) is a systematically constructed procedure whereby environmental impacts caused by proposed projects are examined. Geographical Information Systems (GIS) are crucially efficient tools for impact assessment and their use is likely to dramatically increase in the near future. GIS have been applied to a wide range of different impact assessment projects and dams among them have been taken as the case work in this article. EIA Regulation in force in Turkey requires the analysis of steering natural processes that can be adversely affected by the proposed project, particularly in the section of the analysis of the areas with higher landscape value. At this point, the true potential value of GIS lies in its ability to analyze spatial data with accuracy. This study is an attempt to analyze by GIS the areas with higher landscape value in the impact assessment of dam constructions in the case of Seyhan-Köprü Hydroelectric Dam project proposal. A method needs to be defined before the overlapping step by GIS to analyze the areas with higher landscape value. In the case of Seyhan-Köprü Hydroelectric Dam project proposal of the present work, considering the geological conditions and the steep slopes of the area and the type of the project, the most important natural process is erosion. Therefore, the areas of higher erosion risk were considered as the Areas with Higher Landscape Value from the conservation demands points of view.

Estimating inbreeding rates in natural populations: Addressing the problem of incomplete pedigrees

USGS Publications Warehouse

Miller, Mark P.; Haig, Susan M.; Ballou, Jonathan D.; Steel, E. Ashley

2017-01-01

Understanding and estimating inbreeding is essential for managing threatened and endangered wildlife populations. However, determination of inbreeding rates in natural populations is confounded by incomplete parentage information. We present an approach for quantifying inbreeding rates for populations with incomplete parentage information. The approach exploits knowledge of pedigree configurations that lead to inbreeding coefficients of F = 0.25 and F = 0.125, allowing for quantification of Pr(I|k): the probability of observing pedigree I given the fraction of known parents (k). We developed analytical expressions under simplifying assumptions that define properties and behavior of inbreeding rate estimators for varying values of k. We demonstrated that inbreeding is overestimated if Pr(I|k) is not taken into consideration and that bias is primarily influenced by k. By contrast, our new estimator, incorporating Pr(I|k), is unbiased over a wide range of values of kthat may be observed in empirical studies. Stochastic computer simulations that allowed complex inter- and intragenerational inbreeding produced similar results. We illustrate the effects that accounting for Pr(I|k) can have in empirical data by revisiting published analyses of Arabian oryx (Oryx leucoryx) and Red deer (Cervus elaphus). Our results demonstrate that incomplete pedigrees are not barriers for quantifying inbreeding in wild populations. Application of our approach will permit a better understanding of the role that inbreeding plays in the dynamics of populations of threatened and endangered species and may help refine our understanding of inbreeding avoidance mechanisms in the wild.

Knowledge and acceptability of alternative HIV prevention bio-medical products among MSM who bareback.

PubMed

Nodin, N; Carballo-Diéguez, A; Ventuneac, A M; Balan, I C; Remien, R

2008-01-01

Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Seventy-two men who have sex with men (MSM) who took part in a study on Internet use and intentional condomless anal intercourse were asked about these four products during a semi-structured interview. The questions explored knowledge and acceptability of all the products and willingness to participate in microbicide and vaccine trials. Qualitative analysis of the data suggests that these men had virtually no knowledge of PrEP, very limited knowledge of microbicides, some information about PEP and considerably more knowledge about vaccines. Reactions towards the products were generally positive except for PrEP, for which reactions were polarized as either enthusiastic or negative. With the exception of PrEP, many men expressed willingness to use the products in the future. Most men would be willing to participate in trials for microbicides and vaccines if given basic reassurances. Concerns over negative side effects and preoccupation with possible infection were some of the motives given for non-willingness to participate in a vaccine trial. These results should inform the development of future trials of biomedical prevention products.

A Ground Validation Network for the Global Precipitation Measurement Mission

NASA Technical Reports Server (NTRS)

Schwaller, Mathew R.; Morris, K. Robert

2011-01-01

A prototype Validation Network (VN) is currently operating as part of the Ground Validation System for NASA's Global Precipitation Measurement (GPM) mission. The VN supports precipitation retrieval algorithm development in the GPM prelaunch era. Postlaunch, the VN will be used to validate GPM spacecraft instrument measurements and retrieved precipitation data products. The period of record for the VN prototype starts on 8 August 2006 and runs to the present day. The VN database includes spacecraft data from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and coincident ground radar (GR) data from operational meteorological networks in the United States, Australia, Korea, and the Kwajalein Atoll in the Marshall Islands. Satellite and ground radar data products are collected whenever the PR satellite track crosses within 200 km of a VN ground radar, and these data are stored permanently in the VN database. VN products are generated from coincident PR and GR observations when a significant rain event occurs. The VN algorithm matches PR and GR radar data (including retrieved precipitation data in the case of the PR) by calculating averages of PR reflectivity (both raw and attenuation corrected) and rain rate, and GR reflectivity at the geometric intersection of the PR rays with the individual GR elevation sweeps. The algorithm thus averages the minimum PR and GR sample volumes needed to "matchup" the spatially coincident PR and GR data types. The result of this technique is a set of vertical profiles for a given rainfall event, with coincident PR and GR samples matched at specified heights throughout the profile. VN data can be used to validate satellite measurements and to track ground radar calibration over time. A comparison of matched TRMM PR and GR radar reflectivity factor data found a remarkably small difference between the PR and GR radar reflectivity factor averaged over this period of record in stratiform and convective rain cases when samples were taken from high in the atmosphere. A significant difference in PR and GR reflectivity was found in convective cases, particularly in convective samples from the lower part of the atmosphere. In this case, the mean difference between PR and corrected GR reflectivity was -1.88 dBZ. The PR-GR bias was found to increase with the amount of PR attenuation correction applied, with the PR-GR bias reaching -3.07 dBZ in cases where the attenuation correction applied is greater than 6 dBZ. Additional analysis indicated that the version 6 TRMM PR retrieval algorithm underestimates rainfall in case of convective rain in the lower part of the atmosphere by 30%-40%.

The Epiphytic Fungus Pseudozyma aphidis Induces Jasmonic Acid- and Salicylic Acid/Nonexpressor of PR1-Independent Local and Systemic Resistance1[C][W

PubMed Central

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-01-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the ‎‎collapse of powdery ‎mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants’ defense machinery via local and systemic induction of PATHOGENESIS-RELATED1 (PR1) and PLANT DEFENSIN1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well. PMID:23388119

The epiphytic fungus Pseudozyma aphidis induces jasmonic acid- and salicylic acid/nonexpressor of PR1-independent local and systemic resistance.

PubMed

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-04-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the collapse of powdery mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants' defense machinery via local and systemic induction of pathogenesis-related1 (PR1) and plant defensin1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well.

Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro.

PubMed

Workman, Rob G; Maddison, Ben C; Gough, Kevin C

2017-07-04

Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system protein misfolding cyclic amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.

Cancer Care Coordinators to Improve Tamoxifen Persistence in Breast Cancer: How Heterogeneity in Baseline Prognosis Impacts on Cost-Effectiveness.

PubMed

Nair, Nisha; Kvizhinadze, Giorgi; Blakely, Tony

2016-12-01

To assess the cost-effectiveness of a cancer care coordinator (CCC) in helping women with estrogen receptor positive (ER+) early breast cancer persist with tamoxifen for 5 years. We investigated the cost-effectiveness of a CCC across eight breast cancer subtypes, defined by progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and local/regional spread. These subtypes range from excellent to poorer prognoses. The CCC helped in improving tamoxifen persistence by providing information, checking-in by phone, and "troubleshooting" concerns. We constructed a Markov macrosimulation model to estimate health gain (in quality-adjusted life-years or QALYs) and health system costs in New Zealand, compared with no CCC. Participants were modeled until death or till the age of 110 years. Some input parameters (e.g., the impact of a CCC on tamoxifen persistence) had sparse evidence. Therefore, we used estimates with generous uncertainty and conducted sensitivity analyses. The cost-effectiveness of a CCC for regional ER+/PR-/HER2+ breast cancer (worst prognosis) was NZ $23,400 (US $15,800) per QALY gained, compared with NZ $368,500 (US $248,800) for local ER+/PR+/HER2- breast cancer (best prognosis). Using a cost-effectiveness threshold of NZ $45,000 (US $30,400) per QALY, a CCC would be cost-effective only in the four subtypes with the worst prognoses. There is value in investigating cost-effectiveness by different subtypes within a disease. In this example of breast cancer, the poorer the prognosis, the greater the health gains from a CCC and the better the cost-effectiveness. Incorporating heterogeneity in a cost-utility analysis is important and can inform resource allocation decisions. It is also feasible to undertake in practice. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Informed decision-making with and for people with dementia - efficacy of the PRODECIDE education program for legal representatives: protocol of a randomized controlled trial (PRODECIDE-RCT).

PubMed

Lühnen, Julia; Haastert, Burkhard; Mühlhauser, Ingrid; Richter, Tanja

2017-09-15

In Germany, the guardianship system provides adults who are no longer able to handle their own affairs a court-appointed legal representative, for support without restriction of legal capacity. Although these representatives only rarely are qualified in healthcare, they nevertheless play decisive roles in the decision-making processes for people with dementia. Previously, we developed an education program (PRODECIDE) to address this shortcoming and tested it for feasibility. Typical, autonomy-restricting decisions in the care of people with dementia-namely, using percutaneous endoscopic gastrostomy (PEG) or physical restrains (PR), or the prescription of antipsychotic drugs (AP)-were the subject areas trained. The training course aims to enhance the competency of legal representatives in informed decision-making. In this study, we will evaluate the efficacy of the PRODECIDE education program. A randomized controlled trial with a six-month follow-up will be conducted to compare the PRODECIDE education program with standard care, enrolling legal representatives (N = 216). The education program lasts 10 h and comprises four modules: A, decision-making processes and methods; and B, C and D, evidence-based knowledge about PEG, PR and AP, respectively. The primary outcome measure is knowledge, which is operationalized as the understanding of decision-making processes in healthcare affairs and in setting realistic expectations about benefits and harms of PEG, PR and AP in people with dementia. Secondary outcomes are sufficient and sustainable knowledge and percentage of persons concerned affected by PEG, FEM or AP. A qualitative process evaluation will be performed. Additionally, to support implementation, a concept for translating the educational contents into e-learning modules will be developed. The study results will show whether the efficacy of the education program could justify its implementation into the regular training curricula for legal representatives. Additionally, it will determine whether an e-learning course provides a valuable backup or even alternative learning strategy. TRN: ISRCTN17960111 , Date: 01/06/2017.

Prostate Cancer Information Available in Health-Care Provider Offices: An Analysis of Content, Readability, and Cultural Sensitivity.

PubMed

Choi, Seul Ki; Seel, Jessica S; Yelton, Brooks; Steck, Susan E; McCormick, Douglas P; Payne, Johnny; Minter, Anthony; Deutchki, Elizabeth K; Hébert, James R; Friedman, Daniela B

2018-07-01

Prostate cancer (PrCA) is the most common cancer affecting men in the United States, and African American men have the highest incidence among men in the United States. Little is known about the PrCA-related educational materials being provided to patients in health-care settings. Content, readability, and cultural sensitivity of materials available in providers' practices in South Carolina were examined. A total of 44 educational materials about PrCA and associated sexual dysfunction was collected from 16 general and specialty practices. The content of the materials was coded, and cultural sensitivity was assessed using the Cultural Sensitivity Assessment Tool. Flesch Reading Ease, Flesch-Kincaid Grade Level, and the Simple Measure of Gobbledygook were used to assess readability. Communication with health-care providers (52.3%), side effects of PrCA treatment (40.9%), sexual dysfunction and its treatment (38.6%), and treatment options (34.1%) were frequently presented. All materials had acceptable cultural sensitivity scores; however, 2.3% and 15.9% of materials demonstrated unacceptable cultural sensitivity regarding format and visual messages, respectively. Readability of the materials varied. More than half of the materials were written above a high-school reading level. PrCA-related materials available in health-care practices may not meet patients' needs regarding content, cultural sensitivity, and readability. A wide range of educational materials that address various aspects of PrCA, including treatment options and side effects, should be presented in plain language and be culturally sensitive.

Ferromagnetism in a hexagonal PrRh3 with 4f2 configuration

NASA Astrophysics Data System (ADS)

Park, G. B.; Yamane, Y.; Onimaru, T.; Umeo, K.; Takabatake, T.

2018-05-01

Electrical resistivity ρ , magnetization M and specific heat C are reported for polycrystalline samples of the hexagonal system PrRh3. The magnetic susceptibility M/B obeys the Curie-Weiss law with the effective magnetic moment μeff = 3.88 μB/Pr and the paramagnetic Curie temperature θp = +2.9 K, which indicates ferro-type magnetic interaction between the trivalent Pr ions. A cusp in C(T) at 3.0 K coincides with a bend in ρ (T). Applying magnetic fields, the peak broadens and shifts to higher temperatures. The field dependence indicates a ferro-type magnetic order. The magnetic entropy Sm is (1/3)Rln2 at TC = 3.0 K, suggesting that part of the Pr ions take part in the magnetic order. A broad tail of the magnetic specific heat Cm observed above TC may result from short-range correlations and/or fluctuations of the active magnetic dipole and quadrupoles in the ground state doublet.

Potential approaches for heterologous prion protein treatment of prion diseases

PubMed Central

Seelig, Davis M.; Goodman, Patricia A.; Skinner, Pamela J.

2016-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system. PMID:26636482

Prion protein induced signaling cascades in monocytes

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

Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Ruediger

2006-02-03

Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP{sup C}), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP{sup C} fusion proteins synthesized with a human Fc-tag. PrP{sup C} fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signalingmore » pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK{sub 1,2} and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP{sup C} in monocytes and macrophages.« less

Præventis, the immunisation register of the Netherlands: a tool to evaluate the National Immunisation Programme.

PubMed

van Lier, A; Oomen, P; de Hoogh, P; Drijfhout, I; Elsinghorst, B; Kemmeren, J; Conyn-van Spaendonck, M; de Melker, H

2012-04-26

Vaccination coverage is an important performance indicator of any national immunisation programme (NIP). To monitor the vaccination coverage in the Netherlands, an electronic national immunisation register called ‘Præventis’ was implemented in 2005. Præventis has a link with the population register and can produce letters of invitation for the NIP, register and validate administered vaccinations. The database is used to monitor the vaccination process, produce reminder letters, control the stock of vaccines and provides information used for paying the fees to the different executive organisations involved. Præventis provides a crucial tool for the evaluation of the NIP by producing (sub)national vaccination coverage estimates with high accuracy and allowing additional research: identifying populations at high risk for low coverage based on existing data, conducting specific studies where individuals included in the immunisation register are approached for further research, using vaccination coverage data for the interpretation of (sero)surveillance data, and linking the immunisation register with disease registers to address vaccine safety or vaccine effectiveness. The ability to combine Præventis data with data from other databases or disease registers and the ability to approach individuals with additional research questions offers opportunities to identify areas of priority for improving the Dutch NIP.

Prion protein degradation by lichens of the genus Cladonia

USGS Publications Warehouse

Bennett, James P.; Rodriguez, Cynthia M.; Johnson, Christopher J.

2012-01-01

It has recently been discovered that lichens contain a serine protease capable of degrading the pathogenic prion protein, the etiological agent of prion diseases such as sheep scrapie and cervid chronic wasting disease. Limited methods are available to degrade or inactivate prion disease agents, especially in the environment, and lichens or their serine protease could prove important for management of these diseases. Scant information is available regarding the presence or absence of the protease responsible for degrading prion protein (PrP) in lichen species and, in this study, we tested the hypothesis that PrP degradation activity in lichens is phylogenetically-based by testing 44 species of Cladonia lichens, a genus for which a significant portion of the phylogeny is well established. We categorized PrP degradation activity among the 44 species (high, moderate, low or none) and found that activity in Cladonia species did not correspond with phylogenetic position of the species. Degradation of PrP did correspond, however, with three classical taxonomic characters within the genus: species with brown apothecia, no usnic acid, and the presence of a cortex. Of the 44 species studied, 18 (41%) had either high or moderate PrP degradation activity, suggesting the protease may be frequent in this genus of lichens.

75 FR 68529 - Proposed Christmas Tree Promotion, Research, and Information Order; Referendum Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-08

...-0008-PR] RIN 0581-AD00 Proposed Christmas Tree Promotion, Research, and Information Order; Referendum...) is favored by domestic producers and importers of Christmas trees. This proposed program would be... received a proposal for a national research and promotion program for Christmas trees from the Christmas...

77 FR 23713 - Pesticides; Final Guidance on Material Safety Data Sheets as Pesticide Labeling; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... pesticides registered under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and the Material... the information collection activities and related burden estimates associated with the guidance provided in PR Notice 2012-1. DATES: Comments on the Agency's information collection activities and related...

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

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

Tao, Ye; Chen, Tao; Liu, Bei

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retinamore » were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. • Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. • The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models. • The MEA information would enrich our knowledge about the pathology of MNU induced RP models.« less

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study.

PubMed

Marra, Elske; Hankins, Catherine A

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the Netherlands explored perceptions of MSM and their willingness to use oral PrEP and rectal microbicides (RM) if made available. Recruited through social media (Facebook and Twitter), 108 MSM completed online questionnaires. Seven of them consented to discuss the survey results in semi-structured interviews. Survey participants preferred a RM that could be applied before and after anal intercourse (60.8%) to daily oral PrEP (20.3%). This preference was based on anticipated user friendliness, hypothetically fewer expected adverse events, and perceptions that RM would be less likely to be confused with ARVs for treatment. Those who preferred oral PrEP had stronger beliefs in the effectiveness of pills, perceived its use as easy, and viewed not requiring sexual partner awareness as advantages. No predictive factors were found for the choice of one prevention method over the other. Although Dutch MSM perceive both oral and topical PrEP positively, many barriers exist to the introduction of these products in the Netherlands. These include lack of regulatory approval of oral PrEP, no proven efficacy as yet for RM, and strong HIV stigma within the MSM population. In-depth qualitative research is needed to further explore the perceptions of MSM to inform implementation of programmes should these HIV prevention methods become available.

Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma

PubMed Central

Pareja, Fresia; Murray, Melissa P; Jean, Ryan Des; Konno, Fumiko; Friedlander, Maria; Lin, Oscar; Edelweiss, Marcia

2016-01-01

BACKGROUND Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. METHODS We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. RESULTS We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). CONCLUSION The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER. PMID:28529880

Thermopower of CexR1-xB6 (R=La, Pr and Nd)

NASA Astrophysics Data System (ADS)

Kim, Moo‑Sung; Nakai, Yuki; Tou, Hideki; Sera, Masafumi; Iga, Fumitoshi; Takabatake, Toshiro; Kunii, Satoru

2006-06-01

The thermopower, S, of CexR1-xB6 (R=La, Pr, Nd) was investigated. S with a positive sign shows a typical behavior observed in the Ce Kondo system, an increase with decreasing temperature at high temperatures and a maximum at low temperatures. The S values of all the systems at high temperatures are roughly linearly dependent on the Ce concentration, indicating the conservation of the single-impurity character of the Kondo effect in a wide x range. However, the maximum value of S, Smax, and the temperature, Tmax, at which Smax is observed exhibit different x dependences between CexLa1-xB6 and CexR1-xB6 (R=Pr, Nd). In CexLa1-xB6, Tmax, which is ˜8 K in CeB6, decreases with decreasing x and converges to ˜1 K in a very dilute alloy and Smax shows an increase below x ˜ 0.1 after decreasing with decreasing x. In CexR1-xB6 (R=Pr, Nd), Tmax shows a weak x dependence but Smax shows a roughly linear decrease in x. These results are discussed from the standpoint of the chemical pressure effect and the Ce-Ce interaction. S in the long-range ordered phase shows very different behaviors between CexPr1-xB6 and CexNd1-xB6.

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

PubMed Central

Hsiao, K K; Groth, D; Scott, M; Yang, S L; Serban, H; Rapp, D; Foster, D; Torchia, M; Dearmond, S J; Prusiner, S B

1994-01-01

Two lines of transgenic (Tg) mice expressing high (H) levels of the mutant P101L prion protein (PrP) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogenates from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD-1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximately 10% of hamsters and approximately 40% of the Tg196 mice manifested neurologic signs between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated with brain extracts, producing incubation times of approximately 400 and approximately 75 days, respectively. Although the Tg(MoPrP-P101L)H mice appear to accumulate only low levels of infections prions in their brains, the serial transmission of disease to inoculated recipients argues that prion formation occurs de novo in the brains of these uninoculated animals. These Tg mouse studies, taken together with similar findings in humans dying of inherited prion diseases, provide additional evidence that prions lack a foreign nucleic acid. Images PMID:7916462

Morphological Simulation of Phase Separation Coupled Oscillation Shear and Varying Temperature Fields

NASA Astrophysics Data System (ADS)

Wang, Heping; Li, Xiaoguang; Lin, Kejun; Geng, Xingguo

2018-05-01

This paper explores the effect of the shear frequency and Prandtl number ( Pr) on the procedure and pattern formation of phase separation in symmetric and asymmetric systems. For the symmetric system, the periodic shear significantly prolongs the spinodal decomposition stage and enlarges the separated domain in domain growth stage. By adjusting the Pr and shear frequency, the number and orientation of separated steady layer structures can be controlled during domain stretch stage. The numerical results indicate that the increase in Pr and decrease in the shear frequency can significantly increase in the layer number of the lamellar structure, which relates to the decrease in domain size. Furthermore, the lamellar orientation parallel to the shear direction is altered into that perpendicular to the shear direction by further increasing the shear frequency, and also similar results for larger systems. For asymmetric system, the quantitative analysis shows that the decrease in the shear frequency enlarges the size of separated minority phases. These numerical results provide guidance for setting the optimum condition for the phase separation under periodic shear and slow cooling.

Photoemission study of the electronic structure (Pr 0.2La 0.8)(Ba 1.875La 0.125)Cu 3O 7- gd

NASA Astrophysics Data System (ADS)

Lindberg, P. A. P.; Shen, Z.-X.; Lindau, I.; Spicer, W. E.; Mitzi, D. B.; Kapitulnik, A.

1989-11-01

Photoemission results from the Pr and La doped 1 2 3 system (Pr 0.2La 0.8) (Ba 1.875La 0.125)Cu 3O 7-gd are reported. The core level spectra show strong resemblance to those of other compounds of the 1 2 3 and 2 1 4 systems. The Cu 2 p satellite intensity is found to be ˜ 35% of the main Cu 2 p line, and the O 1 s core level spectra, exhibiting a clear doublet, show evidence of extrinsic oxygen. The clear correlation between the intensities of certain features in the valence band and the amount of extrinsic oxygen, as monitored by the O 1 s core level spectra, is explicitly addressed.

Pellet Puzzlers.

ERIC Educational Resources Information Center

Hoots, R. A.

1992-01-01

Presents information on owl's taxonomy, characteristics, and influences on man. Describes owl pellets, which are digestive discards, and explains how they can be used to determine the owl's diet as a science activity. (PR)

Bioluminescence.

ERIC Educational Resources Information Center

Jones, M. Gail

1993-01-01

Describes bioluminescence and the chemistry of how it occurs. Presents information for conducting the following classroom activities: (1) firefly mimic; (2) modeling deep-sea fish; (3) sea fireflies; and (4) the chemistry of light. (PR)

Looking at the Cell Once Again.

ERIC Educational Resources Information Center

Flannery, Maura C.

1993-01-01

Summarizes current information on the cell for the following topics: mitochondria from the male, moving cells, the cell cycle, the kinetics of kinetechore, nuclear structure, and sorting and secretion. (PR)

Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.

PubMed

Bacot, Silvia M; Feldman, Gerald M; Yamada, Kenneth M; Dhawan, Subhash

2015-02-01

Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis. Published by Elsevier Inc.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure.

PubMed

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

2015-01-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

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

Wan, William; Stöhr, Jan; Kendall, Amy

2015-09-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled themore » complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.« less

Targeted drug delivery and enhanced intracellular release using functionalized liposomes

NASA Astrophysics Data System (ADS)

Garg, Ashish

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5-fluorouracil (5-FU) show significantly higher cytotoxicity than the PR_b-targeted inert stealth liposomes and the non-targeted stealth liposomes (both pH-sensitive and inert). The studies demonstrated that optimized PR_b functionalized pH sensitive liposomes have the potential to deliver a payload, such as chemotherapeutic agents, directly to colon cancer cells in an efficient and specific manner.

The Puerto Rico Component of the National Tsunami Hazard and Mitigation Program Pr-Nthmp

NASA Astrophysics Data System (ADS)

Huerfano Moreno, V. A.; Hincapie-Cardenas, C. M.

2014-12-01

Tsunami hazard assessment, detection, warning, education and outreach efforts are intended to reduce losses to life and property. The Puerto Rico Seismic Network (PRSN) is participating in an effort with local and federal agencies, to developing tsunami hazard risk reduction strategies under the National Tsunami Hazards and Mitigation Program (NTHMP). This grant supports the TsunamiReady program which is the base of the tsunami preparedness and mitigation in PR. The Caribbean region has a documented history of damaging tsunamis that have affected coastal areas. The seismic water waves originating in the prominent fault systems around PR are considered to be a near-field hazard for Puerto Rico and the Virgin islands (PR/VI) because they can reach coastal areas within a few minutes after the earthquake. Sources for local, regional and tele tsunamis have been identified and modeled and tsunami evacuation maps were prepared for PR. These maps were generated in three phases: First, hypothetical tsunami scenarios on the basis of the parameters of potential underwater earthquakes were developed. Secondly, each of these scenarios was simulated. The third step was to determine the worst case scenario (MOM). The run-ups were drawn on GIS referenced maps and aerial photographs. These products are being used by emergency managers to educate the public and develop mitigation strategies. Online maps and related evacuation products are available to the public via the PR-TDST (PR Tsunami Decision Support Tool). Currently all the 44 coastal municipalities were recognized as TsunamiReady by the US NWS. The main goal of the program is to declare Puerto Rico as TsunamiReady, including two cities that are not coastal but could be affected by tsunamis. Based on these evacuation maps, tsunami signs were installed, vulnerability profiles were created, communication systems to receive and disseminate tsunami messages were installed in each TWFP, and tsunami response plans were approved. Also, the existing tsunami protocol and criteria in the PR/VI was updated. This paper describes the PR-NTHMP project, including the real time earthquake and tsunami monitoring as well as the specific protocols used to broadcast tsunami messages. The paper highlights tsunami hazards assessment, detection, warning, education and outreach in Puerto Rico.

The role of male partners in women's participation in research during pregnancy: a case study from the partners demonstration project.

PubMed

Ngure, Kenneth; Trinidad, Susan Brown; Beima-Sofie, Kristin; Baeten, Jared M; Mugo, Nelly R; Bukusi, Elizabeth A; Heffron, Renee; John-Stewart, Grace; Kelley, Maureen C

2017-12-14

The exclusion of pregnant women from health research remains a significant challenge globally. In settings where cultural traditions and gender norms support a more restricted decision-making role for women in general, little is known about the attitudes of male partners toward the inclusion of women in research during pregnancy. Understanding the expectations of both men and women in such cultural settings offers an opportunity to engage and address local ethical concerns to improve women's access to research during pregnancy and enhance intervention development. In this paper, we present a qualitative research ethics case study, drawn from the Partners Demonstration Project of pre-exposure prophylaxis (PrEP) in Kenya, regarding the role of male partners in decision-making to continue PrEP during pregnancy. PrEP is an effective HIV prevention tool; however, since pregnant women were excluded from early PrEP clinical trials, safety and efficacy data during pregnancy are limited. Given continued high rates of HIV infection for women, some pregnant women are now being provided with PrEP or are involved in PrEP research. Men and women in our study were equally concerned about the health risks of PrEP to the fetus and depended on healthcare provider guidance to understand these risks. Because the demonstration project enrolled couples, an implicit social expectation for many women's continuation of PrEP during pregnancy was consultation with male partners. Some women reported that consenting to participate was exclusively a woman's decision; however, many reported that they deferred to their male partner's opinion and support during the decision-making process. Most male partners believed women should not participate in research studies without their partner's permission, while a few men believed participation was ultimately a woman's decision. We suggest that relational autonomy can support a middle ground for informed consent that promotes women's autonomy while accommodating partner engagement.

Gender differences in the association between lifestyle behaviors and diabetes distress in a community sample of adults with type 2 diabetes.

PubMed

Lipscombe, Carla; Smith, Kimberley J; Gariepy, Geneviève; Schmitz, Norbert

2016-03-01

The present study examined the association between moderate and severe diabetes distress (DD) and lifestyle behaviors (physical activity, smoking, alcohol consumption) in a community sample of adults with type 2 diabetes mellitus (T2DM). A total of 1971 adults with T2DM were recruited using mixed methods sampling. Participants were considered eligible if they had a doctor diagnosis of T2DM (≤10 years), were insulin naïve, aged 40-75 years, and were from Quebec, Canada. Participants provided information on DD, lifestyle behaviors, sociodemographic, and diabetes-related factors. Multinomial logistic regressions examined the association between moderate and severe DD and each lifestyle behavior, according to gender. Effect estimates can be interpreted as probability ratios (PR). In females, physical inactivity was associated with an increased likelihood of moderate distress (PR 2.2; 95% confidence interval [CI] 1.49-3.24) and severe distress (PR 1.80; 95% CI 1.00-3.24). In males, only severe distress was associated with physical inactivity (PR 1.92; 95% CI 1.00-3.66). Current smoking was associated with a greater probability of severe distress in males (PR 3.0; 95% CI 1.54-5.84) and females (PR 1.32; 95% CI 0.67-2.60); however this effect was stronger in males. No association was found between alcohol consumption and DD in females. In males, frequent alcohol consumption was associated with a reduced probability of moderate (PR 0.56; 95% CI 0.34-0.91) and severe distress (PR 0.47; 95% CI 0.21-1.06). The findings of this study suggest important gender differences in the association between DD and lifestyle behaviors. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight.

PubMed

Rehan, Mohd; Ahmad, Ejaz; Sheikh, Ishfaq A; Abuzenadah, Adel M; Damanhouri, Ghazi A; Bajouh, Osama S; AlBasri, Samera F; Assiri, Mansour M; Beg, Mohd A

2015-01-01

Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use.

Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene—A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight

PubMed Central

Rehan, Mohd; Ahmad, Ejaz; Sheikh, Ishfaq A.; Abuzenadah, Adel M.; Damanhouri, Ghazi A.; Bajouh, Osama S.; AlBasri, Samera F.; Assiri, Mansour M.; Beg, Mohd A.

2015-01-01

Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use. PMID:26379041

The mechanism of monomer transfer between two structurally distinct PrP oligomers

PubMed Central

Armiento, Aurora; Martin, Davy; Lepejova, Nad’a

2017-01-01

In mammals, Prion pathology refers to a class of infectious neuropathologies whose mechanism is based on the self-perpetuation of structural information stored in the pathological conformer. The characterisation of the PrP folding landscape has revealed the existence of a plethora of pathways conducing to the formation of structurally different assemblies with different biological properties. However, the biochemical interconnection between these diverse assemblies remains unclear. The PrP oligomerisation process leads to the formation of neurotoxic and soluble assemblies called O1 oligomers with a high size heterodispersity. By combining the measurements in time of size distribution and average size with kinetic models and data assimilation, we revealed the existence of at least two structurally distinct sets of assemblies, termed Oa and Ob, forming O1 assemblies. We propose a kinetic model representing the main processes in prion aggregation pathway: polymerisation, depolymerisation, and disintegration. The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population. PMID:28746342

The mechanism of monomer transfer between two structurally distinct PrP oligomers.

PubMed

Armiento, Aurora; Moireau, Philippe; Martin, Davy; Lepejova, Nad'a; Doumic, Marie; Rezaei, Human

2017-01-01

In mammals, Prion pathology refers to a class of infectious neuropathologies whose mechanism is based on the self-perpetuation of structural information stored in the pathological conformer. The characterisation of the PrP folding landscape has revealed the existence of a plethora of pathways conducing to the formation of structurally different assemblies with different biological properties. However, the biochemical interconnection between these diverse assemblies remains unclear. The PrP oligomerisation process leads to the formation of neurotoxic and soluble assemblies called O1 oligomers with a high size heterodispersity. By combining the measurements in time of size distribution and average size with kinetic models and data assimilation, we revealed the existence of at least two structurally distinct sets of assemblies, termed Oa and Ob, forming O1 assemblies. We propose a kinetic model representing the main processes in prion aggregation pathway: polymerisation, depolymerisation, and disintegration. The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population.

Merged and corrected 915 MHz Radar Wind Profiler moments

DOE Data Explorer

Jonathan Helmus,Virendra Ghate, Frederic Tridon

2014-06-25

The radar wind profiler (RWP) present at the SGP central facility operates at 915 MHz and was reconfigured in early 2011, to collect key sets of measurements for precipitation and boundary layer studies. The RWP is configured to run in two main operating modes: a precipitation (PR) mode with frequent vertical observations and a boundary layer (BL) mode that is similar to what has been traditionally applied to RWPs. To address issues regarding saturation of the radar signal, range resolution and maximum range, the RWP PR mode is set to operate with two different pulse lengths, termed as short pulse (SP) and long pulse (LP). Please refer to the RWP handbook (Coulter, 2012) for further information. Data from the RWP PR-SP and PR-LP modes have been extensively used to study deep precipitating clouds, especially their dynamical structure as the RWP data does not suffer from signal attenuation during these conditions (Giangrande et al., 2013). Tridon et al. (2013) used the data collected during the Mid-latitude Continental Convective Cloud Experiment (MC3E) to improve the estimation of noise floor of the RWP recorded Doppler spectra.

Development of an Assay for the Detection of PrPres in Blood and Urine Based on PMCA Assay an ELISA Methods

DTIC Science & Technology

2005-09-01

constitute the basis for a TSE diagnostic human plasma assay platform. We have established a collaboration with Biotraces to develop an assay based on...their MPD instrument. One of the problems with the Biotraces ’ test was its inability to detect low levels of recombinant PrP. Biotraces has now succeeded...data and decide based on these new results whether to continue the collaboration with Biotraces . As soon we have reached a decision, we will inform

VLT Data Flow System Begins Operation

NASA Astrophysics Data System (ADS)

1999-06-01

Building a Terabyte Archive at the ESO Headquarters The ESO Very Large Telescope (VLT) is the sum of many sophisticated parts. The site at Cerro Paranal in the dry Atacama desert in Northern Chile is one of the best locations for astronomical observations from the surface of the Earth. Each of the four 8.2-m telescopes is a technological marvel with self-adjusting optics placed in a gigantic mechanical structure of the utmost precision, continuously controlled by advanced soft- and hardware. A multitude of extremely complex instruments with sensitive detectors capture the faint light from distant objects in the Universe and record the digital data fast and efficiently as images and spectra, with a minimum of induced noise. And now the next crucial link in this chain is in place. A few nights ago, following an extended test period, the VLT Data Flow System began providing the astronomers with a steady stream of high-quality, calibrated image and spectral data, ready to be interpreted. The VLT project has entered into a new phase with a larger degree of automation. Indeed, the first 8.2-m Unit Telescope, ANTU, with the FORS1 and ISAAC instruments, has now become a true astronomy machine . A smooth flow of data through the entire system ESO PR Photo 25a/99 ESO PR Photo 25a/99 [Preview - JPEG: 400 x 292 pix - 104k] [Normal - JPEG: 800 x 584 pix - 264k] [High-Res - JPEG: 3000 x 2189 pix - 1.5M] Caption to ESO PR Photo 25a/99 : Simplified flow diagramme for the VLT Data Flow System . It is a closed-loop software system which incorporates various subsystems that track the flow of data all the way from the submission of proposals to storage of the acquired data in the VLT Science Archive Facility. The DFS main components are: Program Handling, Observation Handling, Telescope Control System, Science Archive, Pipeline and Quality Control. Arrows indicate lines of feedback. Already from the start of this project more than ten years ago, the ESO Very Large Telescope was conceived as a complex digital facility to explore the Universe. In order for astronomers to be able to use this marvellous research tool in the most efficient manner possible, the VLT computer software and hardware systems must guarantee a smooth flow of scientific information through the entire system. This process starts when the astronomers submit well-considered proposals for observing time and it ends with large volumes of valuable astronomical data being distributed to the international astronomical community. For this, ESO has produced an integrated collection of software and hardware, known as the VLT Data Flow System (DFS) , that manages and facilitates the flow of scientific information within the VLT Observatory. Early information about this new concept was published as ESO Press Release 12/96 and extensive tests were first carried out at ESOs 3.5-m New Technology Telescope (NTT) at La Silla, cf. ESO Press Release 03/97 [1]. The VLT DFS is a complete (end-to-end) system that guarantees the highest data quality by optimization of the observing process and repeated checks that identify and eliminate any problems. It also introduces automatic calibration of the data, i.e. the removal of external effects introduced by the atmospheric conditions at the time of the observations, as well as the momentary state of the telescope and the instruments. From Proposals to Observations In order to obtain observing time with ESO telescopes, also with the VLT, astronomers must submit a detailed observing proposal to the ESO Observing Programmes Committee (OPC) . It meets twice a year and ranks the proposals according to scientific merit. More than 1000 proposals are submitted each year, mostly by astronomers from the ESO members states and Chile; the competition is fierce and only a fraction of the total demand for observing time can be fulfilled. During the submission of observing proposals, DFS software tools available over the World Wide Web enable the astronomers to simulate their proposed observations and provide accurate estimates of the amount of telescope time they will need to complete their particular scientific programme. Once the proposals have been reviewed by the OPC and telescope time is awarded by the ESO management according to the recommendation by this Committee, the successful astronomers begin to assemble detailed descriptions of their intended observations (e.g. position in the sky, time and duration of the observation, the instrument mode, etc.) in the form of computer files called Observation Blocks (OBs) . The software to make OBs is distributed by ESO and used by the astronomers at their home institutions to design their observing programs well before the observations are scheduled at the telescope. The OBs can then be directly executed by the VLT and result in an increased efficiency in the collection of raw data (images, spectra) from the science instruments on the VLT. The activation (execution) of OBs can be done by the astronomer at the telescope on a particular set of dates ( visitor mode operation) or it can be done by ESO science operations astronomers at times which are optimally suited for the particular scientific programme ( service mode operation). An enormous VLT Data Archive ESO PR Photo 25b/99 ESO PR Photo 25b/99 [Preview - JPEG: 400 x 465 pix - 160k] [Normal - JPEG: 800 x 929 pix - 568k] [High-Res - JPEG: 3000 x 3483 pix - 5.5M] Caption to ESO PR Photo 25b/99 : The first of several DVD storage robot at the VLT Data Archive at the ESO headquarters include 1100 DVDs (with a total capacity of about 16 Terabytes) that may be rapidly accessed by the archive software system, ensuring fast availbility of the requested data. The raw data generated at the telescope are stored by an archive system that sends these data regularly back to ESO headquarters in Garching (Germany) in the form of CD and DVD ROM disks. While the well-known Compact Disks (CD ROMs) store about 600 Megabytes (600,000,000 bytes) each, the new Digital Versatile Disks (DVD ROMs) - of the same physical size - can store up 3.9 Gigabytes (3,900,000,000 bytes) each, or over 6 times more. The VLT will eventually produce more than 20 Gigabytes (20,000,000,000 bytes) of astronomical data every night, corresponding to about 10 million pages of text [2]. Some of these data also pass through "software pipelines" that automatically remove the instrumental effects on the data and deliver data products to the astronomer that can more readily be turned into scientific results. Ultimately these data are stored in a permanent Science Archive Facility at ESO headquarters which is jointly operated by ESO and the Space Telescope European Coordinating Facility (ST-ECF). From here, data are distributed to astronomers on CD ROMs and over the World Wide Web. The archive facility is being developed to enable astronomers to "mine" the large volumes of data that will be collected from the VLT in the coming years. Within the first five years of operations the VLT is expected to produce around 100 Terabytes (100,000,000,000,000 bytes) of data. It is difficult to visualize this enormous amount of information. However, it corresponds to the content of 50 million books of 1000 pages each; they would occupy some 2,500 kilometres of bookshelves! The VLT Data Flow System enters into operation ESO PR Photo 25c/99 ESO PR Photo 25c/99 [Preview - JPEG: 400 x 444 pix - 164k] [Normal - JPEG: 800 x 887 pix - 552k] [High-Res - JPEG: 3000 x 3327 pix - 6.4M] Caption to ESO PR Photo 25c/99 : Astronomers from ESO Data Flow Operations Group at work with the VLT Archive. Science operations with the first VLT 8.2-m telescope ( ANTU ) began on April 1, 1999. Following the first call for proposals to use the VLT in October 1998, the OPC met in December and the observing schedule was finalized early 1999. The related Observation Blocks were prepared by the astronomers in February and March. Service-mode observations began in April and by late May the first scientific programs conducted by ESO science operations were completed. Raw data, instrument calibration information and the products of pipeline processing from these programs have now been assembled and packed onto CD ROMs by ESO science operations staff. On June 15 the first CD ROMs were delivered to astronomers in the ESO community. This event marks the closing of the data flow loop at the VLT for the first time and the successful culmination of more than 5 years of hard work by ESO engineers and scientists to implement a system for efficient and effective scientific data flow. This was achieved by a cross-organization science operations team involving staff in Chile and Europe. With the VLT Data Flow System, a wider research community will have access to the enormous wealth of data from the VLT. It will help astronomers to keep pace with the new technologies and extensive capabilities of the VLT and so obtain world-first scientific results and new insights into the universe. Notes [1] A more technical description of the VLT Data Flow System is available in Chapter 10 of the VLT Whitebook. [2] By definition, one "normal printed page" contains 2,000 characters. How to obtain ESO Press Information ESO Press Information is made available on the World-Wide Web (URL: http://www.eso.org../ ). ESO Press Photos may be reproduced, if credit is given to the European Southern Observatory.

High-resolution, time-resolved MRA provides superior definition of lower-extremity arterial segments compared to 2D time-of-flight imaging.

PubMed

Thornton, F J; Du, J; Suleiman, S A; Dieter, R; Tefera, G; Pillai, K R; Korosec, F R; Mistretta, C A; Grist, T M

2006-08-01

To evaluate a novel time-resolved contrast-enhanced (CE) projection reconstruction (PR) magnetic resonance angiography (MRA) method for identifying potential bypass graft target vessels in patients with Class II-IV peripheral vascular disease. Twenty patients (M:F = 15:5, mean age = 58 years, range = 48-83 years), were recruited from routine MRA referrals. All imaging was performed on a 1.5 T MRI system with fast gradients (Signa LX; GE Healthcare, Waukesha, WI). Images were acquired with a novel technique that combined undersampled PR with a time-resolved acquisition to yield an MRA method with high temporal and spatial resolution. The method is called PR hyper time-resolved imaging of contrast kinetics (PR-hyperTRICKS). Quantitative and qualitative analyses were used to compare two-dimensional (2D) time-of-flight (TOF) and PR-hyperTRICKS in 13 arterial segments per lower extremity. Statistical analysis was performed with the Wilcoxon signed-rank test. Fifteen percent (77/517) of the vessels were scored as missing or nondiagnostic with 2D TOF, but were scored as diagnostic with PR-hyperTRICKS. Image quality was superior with PR-hyperTRICKS vs. 2D TOF (on a four-point scale, mean rank = 3.3 +/- 1.2 vs. 2.9 +/- 1.2, P < 0.0001). PR-hyperTRICKS produced images with high contrast-to-noise ratios (CNR) and high spatial and temporal resolution. 2D TOF images were of inferior quality due to moderate spatial resolution, inferior CNR, greater flow-related artifacts, and absence of temporal resolution. PR-hyperTRICKS provides superior preoperative assessment of lower limb ischemia compared to 2D TOF.

Rectal Pre-Exposure Prophylaxis (PrEP)

PubMed Central

Yang, Haitao; Wang, Lin

2014-01-01

Rectal pre-exposure prophylaxis (PrEP) will be a critical component of HIV prevention products due to the prevalence of unprotected receptive anal intercourse among men who have sex with men and heterosexual couples. Given the biological considerations of this compartment and the complexity of HIV infection, design of a successful rectal microbicide product faces a number of challenges. Important information is being compiled to begin to address deficits in knowledge toward design of rectal PrEP products for men and women. Aspects of formulation development and preclinical and clinical evaluation of rectal products studied to date are summarized in this review. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21–22, 2013. It forms part of a special supplement to Antiviral Research. PMID:24188705

Conformity Adequacy Review: Region 2

EPA Pesticide Factsheets

Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 2 (NJ, NY, PR, VI) is provided here.

Understanding community pharmacist perceptions and knowledge about HIV preexposure prophylaxis (PrEP) therapy in a Mountain West state.

PubMed

Unni, Elizabeth J; Lian, Nadia; Kuykendall, William

2016-01-01

Preexposure prophylaxis (PrEP) therapy is prescribed to HIV-negative individuals who are at high risk of contracting the virus to reduce the risk of transmission. Adherence to therapy is essential for optimal treatment outcome, and community pharmacists have an important role in achieving this through patient counseling. The objectives of this study were to measure pharmacists' actual knowledge about HIV PrEP therapy, perceptions about their HIV PrEP therapy knowledge, and intention to counsel patients about PrEP therapy. A cross-sectional survey was conducted among community pharmacists in Utah to measure their actual knowledge and perceptions of knowledge about PrEP therapy based on the basic information from the Centers for Disease Control website. In addition, the pharmacist's intention to counsel patients on PrEP therapy was measured with the use of the validated Godin 12-item tool. Descriptive analyses and t tests identified characteristics based on gender, degree earned, and years of practice in pharmacy. Regression analysis determined significant predictors of the intention to counsel. There were 251 responses (75% PharmD, 61% male, 42% >10 years' experience as a pharmacist). An exploratory factor analysis of the Godin 12-item tool demonstrated 4 domains: beliefs about capabilities, social influence, moral norms, and intention to counsel patients. There was no difference in the intention to counsel based on gender. Pharmacists with a PharmD and less than 10 years of experience had significantly higher knowledge and intention to counsel. The actual knowledge score of the respondents was significantly higher than their perceptions of their knowledge. Multiple regression results showed that the beliefs about capabilities and social influence were significant predictors of intention to counsel. Educating community pharmacists on PrEP therapy using pharmacists who are considered to be opinion leaders in the pharmacy profession can affect the social influence and beliefs about capabilities domains, which in turn can increase counseling on PrEP therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Prioritizing Risk in Preparation for a Demonstration Project: A Mixed Methods Feasibility Study of Oral Pre-Exposure Prophylaxis (PREP) among Female Sex Workers in South India

PubMed Central

Reza-Paul, Sushena; Lazarus, Lisa; Doshi, Monika; Hafeez Ur Rahman, Syed; Ramaiah, Manjula; Maiya, Raviprakash; MS, Venugopal; Venukumar, K. T.; Sundararaman, Sundar; Becker, Marissa; Moses, Stephen; Lorway, Robert

2016-01-01

Background HIV prevalence among female sex workers (FSWs) in India remains well above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka. Methods From January–April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data. Results Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a “double safety” in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95%) expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%), those who do not use condoms when clients offer more money (58%), who do not consistently use condoms with regular partners (57%), who drink alcohol regularly (49%), and who do not use condoms consistently with clients (48%). Discussion This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means of supporting PrEP uptake and adherence. PMID:27880833

Identification of Alprenolol Hydrochloride as an Anti-prion Compound Using Surface Plasmon Resonance Imaging.

PubMed

Miyazaki, Yukiko; Ishikawa, Takeshi; Kamatari, Yuji O; Nakagaki, Takehiro; Takatsuki, Hanae; Ishibashi, Daisuke; Kuwata, Kazuo; Nishida, Noriyuki; Atarashi, Ryuichiro

2018-04-27

Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein (PrP Sc ) in the central nervous system. Although several small compounds that bind to normal PrP (PrP C ) have been shown to inhibit structural conversion of the protein, an effective therapy for human prion disease remains to be established. In this study, we screened 1200 existing drugs approved by the US Food and Drug Administration (FDA) for anti-prion activity using surface plasmon resonance imaging (SPRi). Of these drugs, 31 showed strong binding activity to recombinant human PrP, and three of these reduced the accumulation of PrP Sc in prion-infected cells. One of the active compounds, alprenolol hydrochloride, which is used clinically as a β-adrenergic blocker for hypertension, also reduced the accumulation of PrP Sc in the brains of prion-infected mice at the middle stage of the disease when the drug was administered orally with their daily water from the day after infection. Docking simulation analysis suggested that alprenolol hydrochloride fitted into the hotspot within mouse PrP C , which is known as the most fragile structure within the protein. These findings provide evidence that SPRi is useful in identifying effective drug candidates for neurodegenerative diseases caused by abnormal protein aggregation, such as prion diseases.

A novel application of PageRank and user preference algorithms for assessing the relative performance of track athletes in competition.

PubMed

Beggs, Clive B; Shepherd, Simon J; Emmonds, Stacey; Jones, Ben

2017-01-01

Ranking enables coaches, sporting authorities, and pundits to determine the relative performance of individual athletes and teams in comparison to their peers. While ranking is relatively straightforward in sports that employ traditional leagues, it is more difficult in sports where competition is fragmented (e.g. athletics, boxing, etc.), with not all competitors competing against each other. In such situations, complex points systems are often employed to rank athletes. However, these systems have the inherent weakness that they frequently rely on subjective assessments in order to gauge the calibre of the competitors involved. Here we show how two Internet derived algorithms, the PageRank (PR) and user preference (UP) algorithms, when utilised with a simple 'who beat who' matrix, can be used to accurately rank track athletes, avoiding the need for subjective assessment. We applied the PR and UP algorithms to the 2015 IAAF Diamond League men's 100m competition and compared their performance with the Keener, Colley and Massey ranking algorithms. The top five places computed by the PR and UP algorithms, and the Diamond League '2016' points system were all identical, with the Kendall's tau distance between the PR standings and '2016' points system standings being just 15, indicating that only 5.9% of pairs differed in their order between these two lists. By comparison, the UP and '2016' standings displayed a less strong relationship, with a tau distance of 95, indicating that 37.6% of the pairs differed in their order. When compared with the standings produced using the Keener, Colley and Massey algorithms, the PR standings appeared to be closest to the Keener standings (tau distance = 67, 26.5% pair order disagreement), whereas the UP standings were more similar to the Colley and Massey standings, with the tau distances between these ranking lists being only 48 (19.0% pair order disagreement) and 59 (23.3% pair order disagreement) respectively. In particular, the UP algorithm ranked 'one-off' victors more highly than the PR algorithm, suggesting that the UP algorithm captures alternative characteristics to the PR algorithm, which may more suitable for predicting future performance in say knockout tournaments, rather than for use in competitions such as the Diamond League. As such, these Internet derived algorithms appear to have considerable potential for objectively assessing the relative performance of track athletes, without the need for complicated points equivalence tables. Importantly, because both algorithms utilise a 'who beat who' model, they automatically adjust for the strength of the competition, thus avoiding the need for subjective decision making.

Associative charge transfer reactions. Temperature effects and mechanism of the gas-phase polymerization of propene initiated by a benzene radical cation.

PubMed

Ibrahim, Yehia; Meot-Ner Mautner, Michael; El-Shall, M Samy

2006-07-13

In associative charge transfer (ACT) reactions, a core ion activates ligand molecules by partial charge transfer. The activated ligand polymerizes, and the product oligomer takes up the full charge from the core ion. In the present system, benzene(+*) (Bz(+*)) reacts with two propene (Pr) molecules to form a covalently bonded ion, C(6)H(6)(+*) + 2 C(3)H(6) --> C(6)H(12)(+*) + C(6)H(6). The ACT reaction is activated by a partial charge transfer from Bz(+*) to Pr in the complex, and driven to completion by the formation of a covalent bond in the polymerized product. An alternative channel forms a stable association product (Bz.Pr)(+*), with an ACT/association product ratio of 60:40% that is independent of pressure and temperature. In contrast to the Bz(+*)/propene system, ACT polymerization is not observed in the Bz(+*)/ethylene (Et) system since charge transfer in the Bz(+*)(Et) complex is inefficient to activate the reaction. The roles of charge transfer in these complexes are verified by ab initio calculations. The overall reaction of Bz(+*) with Pr follows second-order kinetics with a rate constant of k (304 K) = 2.1 x 10(-12) cm(3) s(-1) and a negative temperature coefficient of k = aT(-5.9) (or an activation energy of -3 kcal/mol). The kinetic behavior is similar to sterically hindered reactions and suggests a [Bz(+*) (Pr)]* activated complex that proceeds to products through a low-entropy transition state. The temperature dependence shows that ACT reactions can reach a unit collision efficiency below 100 K, suggesting that ACT can initiate polymerization in cold astrochemical environments.

Effects of the A117V mutation on the folding and aggregation of palindromic sequences (PrP113-120) in prion: insights from replica exchange molecular dynamics simulations.

PubMed

Ning, Lulu; Wang, Qianqian; Zheng, Yang; Liu, Huanxiang; Yao, Xiaojun

2015-02-01

The palindromic region AGAAAAGA (PrP113-120) in prion is highly amyloidogenic and very critical in the structural conversion of cellular prion protein to its pathogenetic form. In this region, there is an important point mutation A117V, which is closely related to the occurrence of Gerstmann-Straussler-Scheinker Syndrome. However, the detailed knowledge about the effects of the A117V mutation on the folding and aggregation of the palindromic sequences is still lacking. To investigate the impacts of A117V mutation on the earliest steps along the PrP113-120 aggregation pathway, replica exchange molecular dynamics simulations of the monomer, 2- and 4-peptide systems of PrP113-120 and its A117V mutant were carried out. The simulations of monomers indicate that both WT and the A117V mutated PrP113-120 are mostly random coils with helical structures transiently populated. Differently, the A117V mutation enhances the intrinsic disorder of PrP113-120. The simulations of 2- and 4-peptide systems of the two species show that the A117V mutation increases the sheet contents and the populations of oligomers, which may be attributed to the enhancement of inter-peptide backbone hydrogen bonding interactions and side chain hydrophobic interactions. Overall, the study provides structural insights into the impacts of the A117V mutation on the folding and assembly of the palindromic sequences, which might be helpful to elucidate the mechanism underlying prion disease and the origin of the Gerstmann-Straussler-Scheinker Syndrome.

Proteolysis suppresses spontaneous prion generation in yeast.

PubMed

Okamoto, Atsushi; Hosoda, Nao; Tanaka, Anri; Newnam, Gary P; Chernoff, Yury O; Hoshino, Shin-Ichi

2017-12-08

Prions are infectious proteins that cause fatal neurodegenerative disorders including Creutzfeldt-Jakob and bovine spongiform encephalopathy (mad cow) diseases. The yeast [ PSI + ] prion is formed by the translation-termination factor Sup35, is the best-studied prion, and provides a useful model system for studying such diseases. However, despite recent progress in the understanding of prion diseases, the cellular defense mechanism against prions has not been elucidated. Here, we report that proteolytic cleavage of Sup35 suppresses spontaneous de novo generation of the [ PSI + ] prion. We found that during yeast growth in glucose media, a maximum of 40% of Sup35 is cleaved at its N-terminal prion domain. This cleavage requires the vacuolar proteases PrA-PrB. Cleavage occurs in a manner dependent on translation but independently of autophagy between the glutamine/asparagine-rich (Q/N-rich) stretch critical for prion formation and the oligopeptide-repeat region required for prion maintenance, resulting in the removal of the Q/N-rich stretch from the Sup35 N terminus. The complete inhibition of Sup35 cleavage, by knocking out either PrA ( pep4 Δ) or PrB ( prb1 Δ), increased the rate of de novo formation of [ PSI + ] prion up to ∼5-fold, whereas the activation of Sup35 cleavage, by overproducing PrB, inhibited [ PSI + ] formation. On the other hand, activation of the PrB pathway neither cleaved the amyloid conformers of Sup35 in [ PSI + ] strains nor eliminated preexisting [ PSI + ]. These findings point to a mechanism antagonizing prion generation in yeast. Our results underscore the usefulness of the yeast [ PSI + ] prion as a model system to investigate defense mechanisms against prion diseases and other amyloidoses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Microstructural, Magnetic, and Optical Properties of Pr-Doped Perovskite Manganite La0.67Ca0.33MnO3 Nanoparticles Synthesized via Sol-Gel Process.

PubMed

Xia, Weiren; Wu, Heng; Xue, Piaojie; Zhu, Xinhua

2018-05-04

We report on microstructural, magnetic, and optical properties of Pr-doped perovskite manganite (La 1 - x Pr x ) 0.67 Ca 0.33 MnO 3 (LPCMO, x = 0.0-0.5) nanoparticles synthesized via sol-gel process. Structural characterizations (X-ray and electron diffraction patterns, (high resolution) TEM images) provide information regarding the phase formation and the single-crystalline nature of the LPCMO systems. X-ray and electron diffraction patterns reveal that all the LPCMO samples crystallize in perovskite crystallography with an orthorhombic structure (Pnma space group), where the MnO 6 octahedron is elongated along the b axis due to the Jahn-Teller effect. That is confirmed by Raman spectra. Crystallite sizes and grain sizes were calculated from XRD and TEM respectively, and the lattice fringes resolved in the high-resolution TEM images of individual LPCMO nanoparticle confirmed its single-crystalline nature. FTIR spectra identify the characteristic Mn-O bond stretching vibration mode near 600 cm - 1 , which shifts towards high wavenumbers with increasing post-annealing temperature or Pr-doping concentration, resulting in further distortion of the MnO 6 octahedron. XPS revealed dual oxidation states of Mn 3+ and Mn 4+ in the LPCMO nanoparticles. UV-vis absorption spectra confirm the semiconducting nature of the LPCMO nanoparticles with optical bandgaps of 2.55-2.71 eV. Magnetic measurements as a function of temperature and magnetic field at field cooling and zero-field cooling modes, provided a Curie temperature around 230 K, saturation magnetization of about 81 emu/g, and coercive field of 390 Oe at 10 K. Such magnetic properties and the semiconducting nature of the LPCMO nanoparticles will make them as suitable candidate for magnetic semiconductor spintronics.

TEAM-UP for quality: a cluster randomized controlled trial protocol focused on preventing pressure ulcers through repositioning frequency and precipitating factors.

PubMed

Yap, Tracey L; Kennerly, Susan M; Horn, Susan D; Bergstrom, Nancy; Datta, Santanu; Colon-Emeric, Cathleen

2018-02-20

Pressure ulcers/injuries (PrUs), a critical concern for nursing homes (NH), are responsible for chronic wounds, amputations, septic infections, and premature deaths. PrUs occur most commonly in older adults and NH residence is a risk factor for their development, with at least one of every nine U.S. NH residents experiencing a PrU and many NHs having high incidence and prevalence rates, in some instances well over 20%. PrU direct treatment costs are greater than prevention costs, making prevention-focused protocols critical. Current PrU prevention protocols recommend repositioning residents at moderate, high, and severe risk every 2 h. The advent of visco-elastic (VE) high-density foam support-surfaces over the past decade may now make it possible to extend the repositioning interval to every 3 or 4 h without increasing PrU development. The TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study aims to determine: 1) whether repositioning interval can be extended for NH residents without compromising PrU incidence and 2) how changes in medical severity interact with changes in risk level and repositioning schedule to predict PrU development. In this proposed cluster randomized study, 9 NHs will be randomly assigned to one of three repositioning intervals (2, 3, or 4 h) for a 4-week period. Each enrolled site will use a single NH-wide repositioning interval as the standard of care for residents at low, moderate, and high risk of PrU development (N = 951) meeting the following criteria: minimum 3-day stay, without PrUs, no adhesive allergy, and using VE support surfaces (mattresses). An FDA-cleared patient monitoring system that records position/movement of these residents via individual wireless sensors will be used to visually cue staff when residents need repositioning and document compliance with repositioning protocols. This study will advance knowledge about repositioning frequency and clinically assessed PrU risk level in relation to PrU incidence and medical severity. Outcomes of this research will contribute to future guidelines for more precise preventive nursing practices and refinement of PrU prevention guidelines. Clinical Trial Registration: NCT02996331 .

Development of an Influenza A Master Virus for Generating High-Growth Reassortants for A/Anhui/1/2013(H7N9) Vaccine Production in Qualified MDCK Cells

PubMed Central

Suzuki, Yasushi; Odagiri, Takato; Tashiro, Masato; Nobusawa, Eri

2016-01-01

In 2013, the first case of human infection with an avian influenza A virus (H7N9) was reported in China, and the human infection with this virus has continued as of 2016. At the request of the WHO, we have successfully developed candidate reassortant vaccine virus using A/Anhui/1/2013 and the high egg-growth master virus A/PR/8/1934. Recent plans regarding influenza vaccine production include using cell-cultured systems in Japan and several other countries. However, egg-based vaccine viruses are not always suitable for cell-cultured vaccine production due to potential issues with growth, protein yield and antigenic stability. Therefore, in this study, we have developed a high-growth master virus (hg-PR8) adapted to qualified NIID-MDCK cells that are competent for vaccine production. The virus hg-PR8 was obtained after 20 serial passages of A/Puerto Rico/8/1934 (PR8) in NIID-MDCK cells. The viral titer of hg-PR8 was 108.6 plaque-forming units per milliliter (PFU/mL). Seven amino acid substitutions were identified in the amino acid sequences of PB2, PB1, PA, NA, M and NS of hg-PR8 compared to the sequence of the original PR8 (org-PR8) strain. The growth capacities of the reassortant viruses, which possess heterologous internal genes from hg-PR8 or org-PR8, indicated that the amino acid changes in PB2 and NS2 similarly affected growth capacity in NIID-MDCK cells. To assess the suitability of hg-PR8 as a master virus, we generated 6:2 reassortant viruses possessing the HA and NA segments from A/Anhui/1/2013 (H7N9) and the remaining segments from hg-PR8. The virus titers of the reassortant strains were 107−108 PFU/mL. The antigenicity of the viruses was stable during ten passages of the viruses in NIID-MDCK cells. In comparison with the egg-based reassortant vaccine viruses with identical HA and NA segments, the hg-PR8-based viruses showed 1.5- to 2-fold higher protein yields in NIID-MDCK cells. PMID:27454606

Genome-Wide Association Studies of the PR Interval in African Americans

PubMed Central

Palmer, Cameron; Meng, Yan A.; Soliman, Elsayed Z.; Musani, Solomon K.; Kerr, Kathleen F.; Schnabel, Renate B.; Lubitz, Steven A.; Sotoodehnia, Nona; Redline, Susan; Pfeufer, Arne; Müller, Martina; Evans, Daniel S.; Nalls, Michael A.; Liu, Yongmei; Newman, Anne B.; Zonderman, Alan B.; Evans, Michele K.; Deo, Rajat; Ellinor, Patrick T.; Paltoo, Dina N.

2011-01-01

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans. PMID:21347284

A multi-center, randomized, clinical trial comparing adhesive polyurethane foam dressing and adhesive hydrocolloid dressing in patients with grade II pressure ulcers in primary care and nursing homes.

PubMed

Guillén-Solà, Mireia; Soler Mieras, Aina; Tomàs-Vidal, Antònia M

2013-12-21

Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14.

Gestational Protein Restriction Increases Angiotensin II Production in Rat Lung1

PubMed Central

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2013-01-01

ABSTRACT Gestational protein restriction (PR) alters the renin-angiotensin system in uterine arteries and placentas and elevates plasma levels of angiotensin II in pregnant rats. To date, how PR increases maternal plasma levels of angiotensin II remains unknown. In this study, we hypothesize that the expression and/or the activity of angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) in lungs, but not kidneys and blood, largely contribute to elevated plasma angiotensin II levels in pregnant rats subject to gestational PR. Time-scheduled pregnant Sprague-Dawley rats were fed a normal or low-protein diet from Day 3 of pregnancy until euthanized at Day 19 or 22. Expressions of Ace and Ace2 (angiotens in I converting enzyme [peptidyl-dipeptidase A] 2) in lungs and kidneys from pregnant rats by quantitative real-time PCR and Western blotting, and the activities of these proteins in lungs, kidneys, and plasma, were measured. The mRNA levels of Ace and Ace2 in lungs were elevated by PR at both Days 19 and 22 of pregnancy. The abundance of ACE protein in lungs was increased, but ACE2 protein was decreased, by PR. The activities of ACE, but not ACE2, in lungs were increased by PR. PR did not change expressions of Ace and Ace2, the activities of both ACE and ACE2 in kidneys, and the abundance and activity of plasma ACE. These findings suggest that maternal lungs contribute to the elevated plasma levels of angiotensin II by increasing both the expression and the activity of ACE in response to gestational PR. PMID:23365412

A Health Profile of Arab Americans in Michigan: A Novel Approach to Using a Hospital Administrative Database.

PubMed

Dallo, Florence J; Ruterbusch, Julie J; Kirma, Joseph David; Schwartz, Kendra; Fakhouri, Monty

2016-12-01

The objectives of this study were to estimate and compare the prevalence of heart disease, cancer, chronic lower respiratory disease, stroke, Alzheimer's, diabetes, nephrosis, flu/pneumonia, hypertension, and atherosclerosis between Arab Americans and whites attending a large, metropolitan hospital system. The sample included 68,047 patients, 18 years of age or older, who visited the hospital during 2012. Demographic and disease variables were electronically abstracted. Demographic characteristics were compared between Arab Americans and whites using Chi square tests. Sex specific, age-adjusted prevalence ratios (PR) and 95 % confidence intervals were estimated for these two groups using a log-binomial regression model. Compared to white men, Arab American men had a higher prevalence of diabetes (PR 1.40, 95 % CI 1.29-1.52) and hypertension (PR 1.07, 95 % CI 1.04-1.10), and a lower prevalence of chronic lower respiratory disease (PR 0.74, 95 % CI 0.66-0.83). Compared to white women, Arab American women had a higher prevalence of chronic lower respiratory disease (PR 1.12, 95 % CI 1.01-1.25), diabetes (PR 1.49, 95 % CI 1.38-1.60), influenza/pneumonia (PR 1.26, 95 % CI 1.05-1.51) and hypertension (PR 1.04, 95 % CI 1.01-1.08). This study supports previous findings that health disparities exist for Arab Americans, who are classified as "white" in health statistics. Standard inclusion of Arab American as a separate ethnicity category will aid researchers in assessing the health care needs of this growing minority community.